(338 days)
NOT_APPLICABLE
No
The document explicitly states "Mentions AI, DNN, or ML: Not Found" and the description of the device focuses on structured therapeutic exercises and lessons, not adaptive or learning algorithms.
Yes
The 'Intended Use / Indications for Use' section explicitly states that "Rejoyn is a prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms." The 'Device Description' further specifies that it delivers a "therapeutic intervention" and is "intended for the treatment of MDD symptoms" and "to reduce MDD symptoms."
No
This device is described as a "prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms." Its intended use is to "reduce MDD symptoms," which indicates a therapeutic rather than a diagnostic function.
Yes
The device is described as a "digital therapeutic smartphone application (app)" and a "prescription smartphone app-based digital therapeutic," explicitly stating it is software administered via the user's smartphone. There is no mention of accompanying hardware components.
Based on the provided information, Rejoyn is not an In Vitro Diagnostic (IVD) device.
Here's why:
- IVD Definition: In Vitro Diagnostics are devices intended for use in the collection, preparation, and examination of specimens taken from the human body (such as blood, urine, or tissue) to provide information for the diagnosis, monitoring, or treatment of diseases or conditions.
- Rejoyn's Function: Rejoyn is a digital therapeutic that delivers a cognitive-emotional and behavioral therapeutic intervention through a smartphone app. It is intended to treat MDD symptoms by providing exercises, lessons, and reinforcement.
- Lack of Specimen Analysis: Rejoyn does not involve the collection, preparation, or analysis of any specimens from the human body. Its interaction is directly with the user through the app interface.
Therefore, Rejoyn falls under the category of a digital therapeutic or software as a medical device (SaMD), but not an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
Rejoyn is a prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older who are on antidepressant medication. It is intended to reduce MDD symptoms.
Product codes
SAP
Device Description
Rejoyn (also known as CT-152) is a digital therapeutic smartphone application (app) for the treatment of Major Depressive Disorder (MDD) symptoms. Rejoyn is a prescription smartphone app-based digital therapeutic administered to a user via the user's smartphone device (running Apple iPhone operating system [iOS®] or Android™ operating system [OS]), which delivers a proprietary interactive cognitiveemotional and behavioral therapeutic intervention. The core components of Rejoyn are the Emotional Faces Memory Task (EFMT) exercises, brief cognitive behavioral therapy (CBT)-based lessons to learn and apply key therapeutic skills, and short message service (SMS) text messaging to reinforce CBT-based lesson content and to encourage engagement with the app. It is intended for the treatment of MDD symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older. It is intended to reduce MDD symptoms.
Rejoyn is designed for use as an adjunct to clinician-managed outpatient care over a period of 6 weeks for the treatment of MDD symptoms, followed by a 4-week extension period where CBT-based lesson content will be accessible but no new therapeutic content or EFMT exercises will be available. Rejoyn is not intended to be used as a stand-alone therapy or as a substitution for the patient's clinician prescribed medications.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adult patients with MDD aged 22 years and older
Intended User / Care Setting
Clinician-managed outpatient care
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The Mirai trial was a pivotal, multicenter, remote, double-blinded (patients also blinded to hypothesis), randomized, controlled trial to evaluate the effectiveness and safety of Rejoyn in adult participants diagnosed with MDD who were on antidepressant therapy (ADT) for the treatment of depression (NCT04770285). The primary objective of Mirai was to evaluate the effectiveness of Rejoyn in reducing depressive symptoms compared with Sham which served as a control. Sham consisted of Shapes Memory Task (SMT) exercise which was matched for time and attention to the active EFMT exercise. In order to retain the intended placebo nature of the Sham, it did not include EFMT or CBT-based content.
The primary efficacy endpoint was the change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score in the Modified Intent-to-Treat (mITT) population. A secondary effectiveness endpoint to evaluate the durability of the effect of Rejoyn was assessed by evaluating changes from baseline to Weeks 8 and 10 in MADRS total score in Rejoyn compared with Sham.
Clinical assessments used to evaluate secondary and exploratory endpoints also included patient-reported outcomes, including the Patient Health Questionnaire-9 (PHQ-9), the clinician-rated Clinical Global Impression-Severity Scale (CGI-S) and the Generalized Anxiety Disorder-7 (GAD-7).
The primary efficacy endpoint was tested at a significance level of 0.049. All other efficacy endpoints, including secondary, exploratory, and post hoc efficacy endpoints, were tested at a nominal 0.05 level (2 sided) without adjusting for multiplicity.
Participants took part in the trial for up to 13 weeks, which included a screening period of up to 3 weeks, a treatment period for 6 weeks, and an extension period for 4 weeks.
Sample Size: Of the 1034 participants screened, 386 were enrolled and randomized to the Rejoyn (N = 194) or Sham app (N = 192) treatment groups (Intent-To-Treat [ITT]). The mITT population comprised 354 participants (N = 177 from both groups) who had 1 session with either treatment and assessments of MADRS total score at both baseline and at least 1 postbaseline timepoint. The Safety Sample comprised 373 participants (Rejoyn: N = 187; Sham: N = 186) who received at least 1 treatment session with either Rejoyn or Sham.
Key Results:
- MADRS - ITT population: Mean change from baseline to Week 6 was -8.78 in Rejoyn group vs -6.66 in Sham group, group difference of -2.12 (p = 0.0211, 95% CI [-3.93, -0.32]).
- MADRS - mITT population: Mean change from baseline to Week 6 was -9.03 in Rejoyn group vs -7.25 in Sham group, group difference of -1.78 (p = 0.0568, 95% CI [-3.60, 0.05]), which was not statistically significant.
- PHQ-9 - ITT population: Mean change from baseline to Week 6 was -6.93 in Rejoyn group vs -5.15 in Sham group, group difference of -1.78 (p = 0.0012 CI [-2.85, -0.71]).
- PHQ-9 - mITT population: Mean change from baseline to Week 6 was -6.68 in Rejoyn group vs -5.10 in Sham group, group difference of -1.58 (p = 0.0029, CI [-2.62, -0.54]).
- CGI-S - ITT population: Mean change from baseline to Week 6 was -1.03 in Rejoyn group vs -0.74 in Sham group, group difference of -0.29 (p = 0.0037, 95% CI [-0.48, -0.09]).
- CGI-S - mITT population: Mean change from baseline to Week 6 was -1.06 in Rejoyn group vs -0.8 in Sham group, group difference of -0.26 (p = 0.0098, 95% CI [-0.46, -0.06]).
- GAD-7 - mITT population: Mean change from baseline to Week 6 was -3.41 in Rejoyn group vs -2.64 in Sham group, group difference of -0.77 (p = 0.0705, 95% CI [-1.61, 0.07]).
- MADRS Anxious Subgroup (mITT, GAD-7 ≥10 at baseline): Mean change from baseline to Week 6 was -9.01 in Rejoyn group vs -5.39 in Sham group, group difference of -3.62 (p = 0.0099, 95% CI [-6.36, -0.88]).
- Durability (MADRS - mITT, Week 10): Mean change from baseline was -10.96 in Rejoyn group vs -9.93 in Sham group, group difference of -1.03 (not clinically significant).
- Overall conclusion: Effectiveness and safety data demonstrate that Rejoyn provides a benefit to patients with MDD when added to antidepressant pharmacotherapy.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Full or Partial Response (≥30% Reduction from baseline at Week 6): ITT: 51.3% (Rejoyn) vs 38.7% (Sham), RR 1.32, p=0.0191. mITT: 48.3% (Rejoyn) vs 37.5% (Sham), RR 1.27, p=0.0485.
- Full Response (≥50% Reduction from baseline at Week 6): ITT: 30.4% (Rejoyn) vs 20.2% (Sham), RR 1.49, p=0.0331. mITT: 28.4% (Rejoyn) vs 20.4% (Sham), RR 1.38, p=0.0884.
- Partial Response (≥30%-50% Reduction from baseline at Week 6): ITT: 20.9% (Rejoyn) vs 18.6% (Sham), RR 1.14, p=0.5619. mITT: 19.9% (Rejoyn) vs 17.0% (Sham), RR 1.15, p=0.5342.
- Remission (≥50% Reduction from baseline and MADRS
§ 882.5801 Computerized behavioral therapy device for psychiatric disorders.
(a)
Identification. A computerized behavioral therapy device for psychiatric disorders is a prescription only device intended to provide a computerized version of condition-specific behavioral therapy as an adjunct to clinician supervised outpatient treatment to patients with psychiatric conditions. The digital therapy is intended to provide patients access to therapy tools used during treatment sessions to improve recognized treatment outcomes.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical data must be provided to fulfill the following:
(i) Describe a validated model of behavioral therapy for the psychiatric disorder; and
(ii) Validate the model of behavioral therapy as implemented by the device.
(2) Software must be described in detail in the software requirements specification (SRS) and software design specification (SDS). Software verification, validation, and hazard analysis must be performed. Software documentation must demonstrate that the device effectively implements the behavioral therapy model.
(3) The following labeling must be provided:
(i) Patient and physician labeling must include instructions for use, including images that demonstrate how to interact with the device.
(ii) Patient and physician labeling must list compatible devices.
(iii) Patient and physician labeling must include a warning that the device is not intended for use as a standalone therapy.
(iv) Patient and physician labeling must include a warning that the device does not represent a substitution for the patient's medication.
(v) Physician labeling must include a summary of the clinical testing with the device.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo has the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 30, 2024
Otsuka America Pharmaceutical, Inc. Nancy Teague Senior Director, Global Regulatory Affairs 2440 Research Boulevard Rockville, Maryland 20850
Re: K231209
Trade/Device Name: Rejoyn Regulation Number: 21 CFR 882.5801 Regulation Name: Computerized Behavioral Therapy Device For Psychiatric Disorders Regulatory Class: Class II Product Code: SAP Dated: March 20, 2024 Received: March 20, 2024
Dear Nancy Teague:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
1
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Pamela D. Scott -S
Pamela D. Scott Assistant Director DHT5B: Division of Neuromodulation and Rehabilitation Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
2
Indications for Use
510(k) Number (if known) K231209
Device Name Rejoyn™
Indications for Use (Describe)
Rejoyn is a prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older who are on antidepressant medication. It is intended to reduce MDD symptoms.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary 4
| 4.1 | Submitter
Submitted by: | Otsuka America Pharmaceutical, Inc. |
|-----|--------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Address: | 2440 Research Blvd.
Rockville, MD 20850 |
| | Telephone: | 240-263-3560 |
| | Fax: | NA |
| | Contact Name: | Nancy F. Teague
Senior Director, Global Regulatory Affairs
Otsuka Pharmaceutical & Commercialization
Development, Inc. (OPDC)
nancy.teague@otsuka-us.com |
| | Date Submitted: | 27 Apr 2023 |
| 4.2 | Device | |
| | Name of Device: | CT-152 |
| | Trade or Proprietary Name: | REJOYNTM |
| | Common or Usual Name: | Prescription Digital Therapeutic |
| | Classification Name: | Computerized Behavioral Therapy Device for
Psychiatric Disorders (21 CFR 882.5801), Class I
(Special Controls) |
| | Regulatory Class: | II |
| | Product Code: | SAP |
| 4.3 | Predicate Device(s) | |
| | Predicate Device Common Name: | reSET® |
| | Predicate Device Manufacturer: | Pear Therapeutics, Inc. |
| | Predicate Device Premarket Notification #: | DEN160018 |
| | Predicate Device Classification: | Computerized Behavioral Therapy Device for
Psychiatric Disorders |
| | Predicate Device Product Code: | SAP (21 CFR 882.5801) |
4
4.4 Device Description
Rejoyn (also known as CT-152) is a digital therapeutic smartphone application (app) for the treatment of Major Depressive Disorder (MDD) symptoms. Rejoyn is a prescription smartphone app-based digital therapeutic administered to a user via the user's smartphone device (running Apple iPhone operating system [iOS®] or Android™ operating system [OS]), which delivers a proprietary interactive cognitiveemotional and behavioral therapeutic intervention. The core components of Rejoyn are the Emotional Faces Memory Task (EFMT) exercises, brief cognitive behavioral therapy (CBT)-based lessons to learn and apply key therapeutic skills, and short message service (SMS) text messaging to reinforce CBT-based lesson content and to encourage engagement with the app. It is intended for the treatment of MDD symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older. It is intended to reduce MDD symptoms.
Rejoyn is designed for use as an adjunct to clinician-managed outpatient care over a period of 6 weeks for the treatment of MDD symptoms, followed by a 4-week extension period where CBT-based lesson content will be accessible but no new therapeutic content or EFMT exercises will be available. Rejoyn is not intended to be used as a stand-alone therapy or as a substitution for the patient's clinician prescribed medications.
4.5 Intended Use/Indications for Use
Intended Use: Rejoyn is a prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older who are on antidepressant medication.
Indications for Use: Rejoyn is a prescription digital therapeutic for the treatment of Major Depressive Disorder (MDD) symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older who are on antidepressant medication. It is intended to reduce MDD symptoms.
Both the Rejoyn and predicate device have the same intended use as computerized behavioral therapy devices for psychiatric disorders, as classified under 21 CFR 882.5801. The Indications for Use statement for Rejoyn is not identical to the predicate device and differ for the psychiatric disorder being treated (ie, MDD for Rejoyn and SUD for reSET). The differences do not alter the intended therapeutic
5
use of the device. The safety and effectiveness of Rejoyn was demonstrated with compliance to all applicable special controls, consistent with the predicate.
Comparison of Technological Characteristics with Predicate 4.6 Device
Rejoyn has similar technological characteristics to reSET, including digital delivery of behavioral therapy through a smartphone application which includes therapeutic content. Additionally, both digital therapies use discrete lessons to deliver CBT. Rejoyn does not include a physician portal whereas reSET does have a physician portal. Both the Patient and Physician Labeling notes that Rejoyn does not monitor the patient's symptoms or clinical status and cannot send or receive alerts or warnings to the prescriber. The data from the Mirai trial reasonably demonstrates that the differences between Rejoyn and the predicate device do not raise new safety and effectiveness questions and Rejoyn is substantially equivalent to the predicate device.
The minor differences in technological characteristics reflect the different clinical needs for the user populations (MDD for Rejoyn and SUD for reSET) and the associated disease-specific content. These differences do not raise new questions of safety and effectiveness.
| Table 4.6-1
Substantial Equivalence Table Comparing Rejoyn to reSET
| (Predicate) | ||
|---|---|---|
| Property or | ||
| Characteristic | Rejoyn | reSET |
| 510(k) Number | K231209 | DEN160018 |
| Food and Drug | ||
| Administration | ||
| (FDA) Product | ||
| Code(s) | SAP | PWE |
| Classification | ||
| Regulation | Computerized behavioral therapy device | |
| for psychiatric disorders | ||
| (21 CFR 882.5801), Class II (Special | ||
| Controls) | Computerized behavioral therapy device for | |
| psychiatric disorders | ||
| (21 CFR 882.5801), Class II (Special | ||
| Controls) |
Table 4.6-1 shows the comparison of characteristics of Rejoyn to the predicate device reSET.
6
| Intended Use | Rejoyn is a prescription digital
therapeutic for the treatment of Major
Depressive Disorder (MDD) symptoms
as an adjunct to clinician-managed
outpatient care for adult patients with
MDD aged 22 years and older who are
on antidepressant medication. | reSET® is a prescription digital therapeutic
intended to deliver CBT to adult patients
with SUD to increase abstinence from
substance use and increase retention in
outpatient therapy programs. |
|------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for
Use | Rejoyn is a prescription digital
therapeutic for the treatment of Major
Depressive Disorder (MDD) symptoms
as an adjunct to clinician-managed
outpatient care for adult patients with
MDD aged 22 years and older who are
on antidepressant medication. It is
intended to reduce MDD symptoms. | reSET® is intended to provide CBT, as
an adjunct to a contingency management
system, for patients 18 years of age and
older who are currently enrolled in
outpatient treatment under the supervision
of a clinician. reSET is indicated as a 12-
week (90 days) prescription-only
treatment for patients with SUD, who are
not currently on opioid replacement
therapy, who do not abuse alcohol solely,
or who do not abuse opioids as their
primary substance of abuse.
It is intended to:
• increase abstinence from a patient's
substances of abuse during treatment,
and
• increase retention in the outpatient
treatment program. |
7
| Table 4.6-1 | Substantial Equivalence Table Comparing Rejoyn to reSET
(Predicate) | |
|--------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Property or
Characteristic | Rejoyn | reSET |
| Device Type | Software as Medical Device (SaMD) | SaMD |
| Access | Rx only | Rx Only |
| Adjunctive
Application | Yes - to antidepressant medication in
addition to treatment as usual (TAU)a | Yes - to Standard of Care (SOC) |
| Target
Conditions | Psychiatric Condition - MDD | Psychiatric Condition - SUD |
| Mechanis
m of
Action | Computerized Behavioral Therapy | Computerized Behavioral Therapy |
| Mobile Platform | Smartphones (iOS and Android) | Smartphones, tablets (iOS and Android) |
| Validated Form
of Behavioral
Therapy | A combination of EFMT and CBT-
based lessons | Community reinforcement approach |
| Technology | Digital therapeutic treatment sessions
(18 EFMT exercises and 18 brief,
CBT-based lessons) over a 6-week
period, followed by a 4-week extension
period where the Rejoyn smartphone
application will remain installed and
the CBT-based lessons available for
optional reference. The EFMT
exercises will not be available during
the extension period. Users will receive
brief SMS messages in the extension
period reminding them of their
previously completed Rejoyn treatment
course. | Digital therapeutic, with 62 total lessons,
including one onboarding lesson, 31 core
therapy lessons, and 30 supplemental lessons
over a 12-week period. |
| Labeling | Patient and physician labeling | Patient and physician labeling |
| Physician Portal | No | Yes |
4.7 Performance Data
Summary of Nonclinical Performance Data 4.7.1
Special controls for device types within computerized behavioral therapy device for psychiatric disorders require that the software must be described in detail in the software requirements specification (SRS) and software design specification (SDS). Software verification, validation, and hazard analysis must be performed. Software documentation must demonstrate that the device effectively implements the behavioral therapy model.
The software documentation provided in the 510(k) is consistent with the FDA Guidance documents entitled "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" dated 11 May 2005, "Content of Premarket Submissions
8
for Device Software Functions" issued on 04 Nov 2021, "Off-the-Shelf Software Use in Medical Devices" dated 27 Sep 2019, and "Content of Premarket Submissions for Management of Cybersecurity in Medical Devices" issued on 02 Oct 2014.
Software verification and validation testing was completed, and software documentation was provided in the 510(k) as recommended by the 2005 FDA guidance for a device of Moderate Level of Concern. Software documentation demonstrates that Rejoyn effectively implements the behavioral therapy model.
Summary of Clinical Performance Data 4.7.2
Special Controls for device types within Computerized Behavioral Therapy Device for Psychiatric Disorders require that clinical data must be provided to:
- (i) Describe a validated model of behavioral therapy for the psychiatric disorder; and
- (ii) Validate the model of behavioral therapy as implemented by the device.
Mirai Trial Design
The Mirai trial was a pivotal, multicenter, remote, double-blinded (patients also blinded to hypothesis), randomized, controlled trial to evaluate the effectiveness and safety of Rejoyn in adult participants diagnosed with MDD who were on antidepressant therapy (ADT) for the treatment of depression (NCT04770285). The primary objective of Mirai was to evaluate the effectiveness of Rejoyn in reducing depressive symptoms compared with Sham which served as a control. Sham consisted of Shapes Memory Task (SMT) exercise which was matched for time and attention to the active EFMT exercise. In order to retain the intended placebo nature of the Sham, it did not include EFMT or CBT-based content.
The primary efficacy endpoint was the change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score in the Modified Intent-to-Treat (mITT) population. A secondary effectiveness endpoint to evaluate the durability of the effect of Rejoyn was assessed by evaluating changes from baseline to Weeks 8 and 10 in MADRS total score in Rejoyn compared with Sham.
Clinical assessments used to evaluate secondary and exploratory endpoints also included patient-reported outcomes, including the Patient Health Questionnaire-9 (PHQ-9), the clinician-rated Clinical Global Impression-Severity Scale (CGI-S) and the Generalized Anxiety Disorder-7 (GAD-7).
The primary efficacy endpoint was tested at a significance level of 0.049. All other efficacy endpoints, including secondary, exploratory, and post hoc efficacy endpoints, were tested at a nominal 0.05 level (2 sided) without adjusting for multiplicity.
9
All procedures for the Mirai trial were conducted virtually, either by telephone or by remote visit via telehealth technology; the screening visit could be performed in person at the discretion of the investigator. Participants took part in the trial for up to 13 weeks, which included a screening period of up to 3 weeks, a treatment period for 6 weeks, and an extension period for 4 weeks.
On Day 1, eligible participants were randomized in a 1:1 ratio to Reioyn or Sham with randomization stratified by trial center. During the treatment period (Day 1 [baseline] to Week 6), participants had remote visits at Weeks 2, 4, and 6 and were contacted by telephone at Weeks 1, 3, and 5. participants were expected to adhere to their digital mobile application exercises, and adherence was monitored during the treatment period. Investigators followed up with participants in both groups who missed sessions and provided reminders to adhere to the session schedule. To evaluate durability of effect after Week 6, participants had remote telehealth visits at Weeks 8 and 10 and were contacted by telephone at Weeks 7 and 9. Participants continued to receive brief text message reminders of the previously completed Rejoyn or Sham treatment course during the extension period (Weeks 7 to 10), retained access to previous CBT-based content and tools (Rejoyn), and continued their ADT. No new digital therapy content was newly introduced or required to be accessed as part of a treatment plan during the extension period. The end of the trial was Week 10.
Participants Disposition
Table 4.7.2-1 summarizes the various analysis sets used in the Mirai Trial. Of the 1034 participants screened, 386 were enrolled and randomized to the Rejoyn (N = 194) or Sham app (N = 192) treatment groups (Intent-To-Treat [ITT]). Demographics characteristics (randomized sample) are shown in Table 4.7.2-2. The mITT population comprised 354 participants (N = 177 from both groups) who had 1 session with either treatment and assessments of MADRS total score at both baseline and at least 1 postbaseline timepoint. The Safety Sample comprised 373 participants (Rejoyn: N = 187; Sham: N = 186) who received at least 1 treatment session with either Rejoyn or Sham. Baseline mean psychiatric evaluation scores for mITT are shown in Table 4.7.2-3.
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| Table 4.7.2-1: Mirai Trial Analysis Sets | |||
|---|---|---|---|
| Sample Size | |||
| Analysis Set | Description | Rejoyn | Sham |
| Intent-To-Treat (ITT) | All randomized patients | 194 | 192 |
| Modified Intent-To-Treat (mITT)* | Randomized patients with | ||
| 1 treatment session | |||
| (Rejoyn or Sham) and | |||
| MADRS assessment at | |||
| baseline and ≥ 1 post- | |||
| baseline timepoint | 177 | 177 | |
| Safety Sample | Randomized patients with | ||
| ≥ 1 treatment session | |||
| (Rejoyn or Sham) | 187 | 186 |
*mITT defined as Full Analysis Set (FAS) in protocol
| Table 4.7.2-2: Demographic Characteristics (Randomized Sample) | |||
|---|---|---|---|
| Demographic | |||
| Characterstic | Rejoyn | ||
| (N=194) | SHAM | ||
| (N=192) | TOTAL | ||
| (N=386) | |||
| Age (yrs) | |||
| n | 194 | 192 | 386 |
| Mean (SD) | 43.0 (12.1) | 42.2 (12.1) | 42.6 (12.1) |
| Median | 43.0 | 41.0 | 42.0 |
| Min, Max | 22,64 | 22,64 | 22,64 |
| Sex [n (%)] | |||
| Male | 29 (14.9%) | 25 (13.0%) | 54 (14.0%) |
| Female | 165 (85.1%) | 167 (87.0%) | 332 (86.0%) |
| Race [n (%)] | |||
| White | 141 (72.7%) | 160 (83.3%) | 301 (78%) |
| Black or African | |||
| American | 36 (18.6%) | 25 (13.0%) | 61 (15.8%) |
| American Indian | |||
| or Alaska Native | 5 (2.6%) | 1 (0.5%) | 6 (1.6%) |
| Asian | 5 (2.6%) | 4 (2.1%) | 9 (2.3%) |
| Native Hawaiian | |||
| or Other Pacific | |||
| Islander | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Other | 7 (3.6%) | 2 (1.0%) | 9 (2.3%) |
| Ethnicity | |||
| Hispanic or Latino | 20 (10.3%) | 16 (8.3%) | 36 (9.3%) |
| Not Hispanic or | |||
| Latino | 173 (89.2%) | 174 (90.6%) | 347 (89.9%) |
| Unknown | 1 (0.5%) | 2 (1.0%) | 3 (0.8%) |
| Cannabis Use [n (%)] | |||
| Yes | 11 (5.7%) | 24 (12.5%) | 35 (9.1%) |
| No | 183 (94.3%) | 168 (87.5%) | 351 (90.9%) |
Max = maximum; Min = minimum
Confidential -- Proprietary Information
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| Table 4.7.2-3: Baseline Mean Psychiatric Evaluation Scores
| (ITT and mITT) | ||||||
|---|---|---|---|---|---|---|
| ITT | mITT | |||||
| Rejoyn | Sham | Total | Rejoyn | Sham | Total | |
| MADRS | 28.4 | 28.5 | 28.4 | 28.5 | 28.4 | 28.4 |
| GAD-7 | 9.5 | 9.7 | 9.6 | 9.6 | 9.6 | 9.6 |
| CGI-S | 4.3 | 4.3 | 4.3 | 4.3 | 4.3 | 4.3 |
| PHQ-9 | 15.4 | 15.2 | 15.3 | 15.3 | 15.1 | 15.2 |
| HAM-D17 | 22.7 | 22.4 | 22.5 | 22.8 | 22.3 | 22.6 |
Safety
Adverse events were directly assessed via phone or video based on the trial being conducted remotely. Adverse events were determined to be related or unrelated to Rejoyn by the investigator. No Treatment Emergent Adverse Event (TEAE) was assessed as related to Reiovn during the trial. There were no discontinuations due to TEAEs. There was one discontinuation due to lack of efficacy in the Sham group. No serious TEAEs occurred during the treatment period. One serious TEAE of transient ischemic attack (assessed as not related to Rejoyn) was reported during the extension period.
The most common TEAEs during the treatment period (all nonserious and not related to Rejoyn) were upper respiratory tract infection (1.1% [n = 2] and 3.2% [n = 6] in Rejoyn and Sham, respectively), nasopharyngitis (1.1% [n = 2] and 2.7% [n= 5] in Rejoyn and Sham. respectively), and headache (2.1% [n = 4] and 1.6% [n = 3] in Rejoyn and Sham, respectively). Headache was the only TEAE that was experienced by at least 2% of subjects in the Rejoyn group at an incidence rate greater than Sham.
During the treatment period, one subject in the Rejoyn group experienced worsening depressive symptoms (based on predefined protocol criteria). In the Rejoyn group, 3.21% (n = 6) of subjects reported clinically important suicidality (based on predefined protocol criteria), compared to 4.84% (n = 9) of subjects in the Sham group. During the extension period, 0.53% (n = 1) of subjects in the Rejoyn group and 1.08% (n = 2) of subjects in the Sham group had clinically important suicidality.
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Summary of Efficacy Results
Overall data from the Mirai Trial indicate that Rejoyn provides benefit to participants with MDD as an adjunct to antidepressant medication. The effectiveness endpoints for both the ITT and mITT populations showed consistent results across patient and clinician-rated scales (see Table 4.7.2-4). More detailed results can also be found in the Clinician Brief Summary.
| ITT | mITT* | |||||||
|---|---|---|---|---|---|---|---|---|
| Outcome | ||||||||
| Measure | Rejoyn | Sham | Between- | |||||
| Group Δ | P-value | Rejoyn | Sham | Between- | ||||
| Group Δ | P-value | |||||||
| MADRS | ||||||||
| Change in | ||||||||
| Total Score | ||||||||
| from Baseline | ||||||||
| to Week 6 | -8.78 | -6.66 | -2.12 | 0.0211† | -9.03 | -7.25 | -1.78 | 0.0568 |
| Full or Partial | ||||||||
| Response‡ | 51.3% | 38.7% | 1.32 RR | 0.0191† | 48.3% | 37.5% | 1.27 RR | 0.0485† |
| Full | ||||||||
| Response§ | 30.4% | 20.2% | 1.49 RR | 0.0331† | 28.4% | 20.4% | 1.38 RR | 0.0884 |
| Partial | ||||||||
| Response¶ | 20.9% | 18.6% | 1.14 RR | 0.5619 | 19.9% | 17.0% | 1.15 RR | 0.5342 |
| Remission# | 18.2% | 13.0% | 1.39 RR | 0.1934 | 17% | 13.6% | 1.24 RR | 0.3901 |
| PHQ-9 | -6.93 | -5.15 | -1.78 | 0.0012†† | -6.68 | -5.10 | -1.58 | 0.0029†† |
| CGI-S | -1.03 | -0.74 | -0.29 | 0.0037†† | -1.06 | -0.80 | -0.26 | 0.0098†† |
Table 4.7.2-4: Efficacy Endpoints in ITT and mITT Populations
*mITT defined as Full Analysis Set (FAS) in protocol and used for the primary efficacy endpoint analysis
t P-value