(308 days)
Not Found
Not Found
No
The summary describes a mechanical knee implant and does not mention any software, algorithms, or data processing that would indicate the use of AI/ML.
Yes
The device is indicated for patients with medial compartment knee osteoarthritis who have failed other treatment modalities and are still experiencing pain that interferes with daily activities, aiming to provide relief and improve function.
No
The MISHATM Knee System is described as a "prescription use, extra-capsular knee implant device." Its purpose is to treat medial compartment knee osteoarthritis, not to diagnose it.
No
The device description explicitly states it is an "extra-capsular knee implant device" comprised of various physical components made of materials like titanium alloy, CoCrMo alloy, polycarbonate urethane, and CFR-PEEK. This indicates it is a hardware device, not software-only.
No, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- IVD Definition: In Vitro Diagnostics are medical devices used to perform tests on samples taken from the human body, such as blood, urine, or tissue, to detect diseases, conditions, or infections.
- Device Description: The provided text describes a surgical implant (the MISHATM Knee System) that is physically placed within the body to treat medial compartment knee osteoarthritis. It is comprised of mechanical components like bases, screws, and absorbers.
- Intended Use: The intended use is to provide relief for patients with knee osteoarthritis by being surgically implanted. This is a therapeutic intervention, not a diagnostic test performed on a sample outside the body.
The description clearly indicates a device used in vivo (within the living body) for treatment, not in vitro (in glass, referring to tests performed outside the body) for diagnosis.
N/A
Intended Use / Indications for Use
The MISHATM Knee System is indicated for patients with medial compartment knee osteoarthritis that have failed to find relief in surgical and/or non-surgical treatment modalities and are still experiencing pain that interferes with activities of daily living and are also unwilling to undergo or ineligible for total knee replacement due to age or absence of advanced osteoarthritis.
Product codes
QVV
Device Description
The MISHATM Knee System (Figure 1) is a prescription use, extra-capsular knee implant device that is comprised of a tibial base subassembly, femoral base subassembly, absorber subassembly, piston subassembly and locking screws. The tibial base subassembly, femoral base subassembly, piston subassembly and absorber subassembly are provided pre-assembled, and the implant is fixed with locking screws to the medial cortices of the distal femur and proximal tibia to share the loads with the knee joint. The articulating ball-and-sockets allow the implant to accommodate the natural motions of the knee. The implant bases and locking screws are made of titanium alloy and the sockets are CoCrMo alloy. The compressive component of the absorber is made of polycarbonate urethane. The femoral balls, tibial balls, and the internal lining of the absorber are made of carbon-fiber-reinforced polyetheretherketone (CFR-PEEK). The implant comes in two sizes (small and large) and right or left configurations.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
knee, distal femur, proximal tibia, medical cortices of the distal femur and proximal tibia
Indicated Patient Age Range
25 to 65 years for the Calypso Knee group and 25 to 80 years for the Control (HTO) group
Intended User / Care Setting
Not Found
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)
Clinical Study:
Study Type: Prospective, multicenter clinical study comparing the Calypso Knee System (rebranded for this De Novo request) to the cohort of subjects treated with High Tibial Osteotomy (HTO) from a non-randomized trial ("GOAL" study-historical data from the Atlas IDE study). Propensity Score (PS) methodology was employed to account for potential selection bias.
Sample Size: PS Analysis set of 81 Calypso subjects and 81 Control (HTO) subjects for data through 24 months post-treatment. A total of eighty-one (81) Calypso subjects and ninety-two (92) Control (HTO) subjects were enrolled; after PS matching, eighty-one (81) Control (HTO) subjects were included.
Key Results:
Primary Endpoint - Composite Clinical Success (CCS) demonstrating noninferiority of the Calypso Knee System to HTO data at 24 months. The success rate was 83.5% for the Calypso Knee group and 57.2% for the Control (HTO) group (using multiple imputation). The non-inferiority study conclusion was robust.
Secondary Endpoints:
- Time to full weight bearing: Calypso 13.4 days, Control 58.0 days.
- WOMAC Pain % Change from Baseline at Month 3: Calypso -55.5%, Control -33.4%.
- WOMAC Pain % Change from Baseline at Month 24: Calypso -76.0%, Control -72.5%.
- WOMAC Function % Change from Baseline at Month 3: Calypso -52.2%, Control -24.3%.
- WOMAC Function % Change from Baseline at Month 24: Calypso -73.9%, Control -67.1%.
Results supported superiority of the Calypso Knee group compared to the Control (HTO) group in four of the five secondary endpoints, with WOMAC Pain % change from Baseline at Month 24 being the exception.
Non-Clinical Mechanical Performance Evaluations (Bench Studies):
- Absorber Unloading Capacity:
- Purpose: Demonstrate minimum compressive resistance force produced by the absorber.
- Performance Criteria: Force >= 15 lbs.
- Results: All specimens exceeded the performance criteria.
- Durability, Wear, and Corrosion Resistance:
- Purpose: Demonstrate implant functionality, wear rate, and corrosion resistance in a simulated in vivo environment.
- Performance Criteria: Mean polymeric wear rate = 10 million simulated gait cycles.
- Results: Mean polymeric wear rate was 0.248 mm³ per one million cycles; mean metallic wear rate was 0.004 mm³ per one million cycles. No evidence of corrosion. All test articles remained functional throughout testing (10.3 million cycles).
- Static Strength:
- Purpose: Demonstrate implant will not fracture or break under clinically relevant loads.
- Performance Criteria: Implant will not fracture or break up to 60 lbs static compressive load.
- Results: All articles survived a static compressive load of 65 lbs without signs of permanent deformation or damage.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Primary Endpoint Success Rate (Composite Clinical Success at 24 months):
- Calypso Knee group: 83.5% (Multiple Imputation)
- Control (HTO) group: 57.2% (Multiple Imputation)
- Secondary Endpoints:
- Time to Full Weight Bearing: Calypso 13.4 days (SD 10.12), Control 58.0 days (SD 39.91)
- WOMAC Pain % Change from Baseline at Month 3: Calypso -55.5% (SD 29.3%), Control -33.4% (SD 35.8%)
- WOMAC Pain % Change from Baseline at Month 24: Calypso -76.0% (SD 28.2%), Control -72.5% (SD 33.0%)
- WOMAC Function % Change from Baseline at Month 3: Calypso -52.2% (SD 32.0%), Control -24.3% (SD 37.0%)
- WOMAC Function % Change from Baseline at Month 24: Calypso -73.9% (SD 29.6%), Control -67.1% (SD 35.8%)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Not Found
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
N/A
0
DE NOVO CLASSIFICATION REQUEST FOR MISHATM KNEE SYSTEM
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Medial knee implanted shock absorber. A medial knee implanted shock absorber is a device implanted outside of the knee capsule extending from the distal femur to the proximal tibia. It is intended to reduce loads on the intra-articular medial joint surface to improve symptoms of osteoarthritis. The device employs a shock absorbing mechanical system and is biomechanically stabilized by plates and screws. The device is not intended to span the lateral knee.
NEW REGULATION NUMBER: 21 CFR 888.3610
CLASSIFICATION: Class II
PRODUCT CODE: QVV
BACKGROUND
DEVICE NAME: MISHATM Knee System
SUBMISSION NUMBER: DEN220033
DATE DE NOVO RECEIVED: July 6, 2022
SPONSOR INFORMATION: Moximed. Inc. 46602 Landing Parkway Fremont, California 94539
INDICATIONS FOR USE
The MISHATM Knee System is indicated as follows:
The MISHATM Knee System is indicated for patients with medial compartment knee osteoarthritis that have failed to find relief in surgical and/or non-surgical treatment modalities and are still experiencing pain that interferes with activities of daily living and are also unwilling to undergo or ineligible for total knee replacement due to age or absence of advanced osteoarthritis.
LIMITATIONS
1
The sale, distribution, and use of the MISHA™ Knee System are restricted to prescription use in accordance with 21 CFR 801.109.
PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
Implant Description
The MISHATM Knee System (Figure 1) is a prescription use, extra-capsular knee implant device that is comprised of a tibial base subassembly, femoral base subassembly, absorber subassembly, piston subassembly and locking screws. The tibial base subassembly, femoral base subassembly, piston subassembly and absorber subassembly are provided pre-assembled, and the implant is fixed with locking screws to the medial cortices of the distal femur and proximal tibia to share the loads with the knee joint. The articulating ball-and-sockets allow the implant to accommodate the natural motions of the knee. The implant bases and locking screws are made of titanium alloy and the sockets are CoCrMo alloy. The compressive component of the absorber is made of polycarbonate urethane. The femoral balls, tibial balls, and the internal lining of the absorber are made of carbon-fiber-reinforced polyetheretherketone (CFR-PEEK). The implant comes in two sizes (small and large) and right or left configurations.
Image /page/1/Picture/5 description: The image shows a medical device, possibly a bone fracture fixation device. It consists of two metal end pieces with multiple holes, connected by a central, cylindrical component. The central component appears to be a telescoping rod, possibly with a spring mechanism inside, and is colored yellow.
Figure 1: MISHATM Knee System Implant
Instrument Description
The instruments for the MISHATM Knee System are used to facilitate targeting, trialing, and fixation of the implant. The instrumentation includes a Fixation Kit, Torque Limiting Driver, and Targeting and Trialing Kits. The Targeting and Trialing kits are intended to support sizing and proper implant selection.
SUMMARY OF NONCLINICAL/BENCH STUDIES
2
BIOCOMPATIBILITY/MATERIALS
The MISHA™ Knee System is manufactured from the following patient contacting materials:
| Description | Material | Direct
Patient
Contact | Contact Duration |
|---------------------------------------|------------------------------------------------------------------------------------------------|------------------------------|-------------------|
| Knee System
Implant | Cobalt Chromium per ASTM
F1537; Ti6Al4V ELI per
ASTM F136; CFR-PEEK, 80A
PCU; 75D PCU | Yes | Permanent (>30 d) |
| Screws | Ti6Al4V ELI per ASTM F136 | Yes | Permanent (>30 d) |
| Patient-
contacting
Instruments | Medical Grade Stainless Steel,
Polycarbonate, and Silicone | Yes | Limited (≤24 h) |
Table 1: Manufactured Materials of Patient-Contacting Device Components
Biocompatibility evaluation has been completed according to 2020 FDA Guidance, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process."
For the permanent implant, Table 2 shows the biocompatibility testing performed and the results, which were acceptable for a permanent implant in contact with bone/tissue:
| Test Description | Result |
|---|---|
| Cytotoxicity (per ISO 10993-5 (Biological evaluation | |
| of medical devices - Part 5: Tests for in vitro | |
| cytotoxicity)) | Non-cytotoxic |
| Irritation (per ISO 10993-10 (Biological evaluation of | |
| medical devices - Part 10: Tests for irritation and skin | |
| sensitization)) | Non-irritant |
| Sensitization (per ISO 10993-10 (Biological evaluation | |
| of medical devices - Part 10: Tests for irritation and | |
| skin sensitization)) | Non-sensitizing |
| Implantation Effects (per ISO 10993-6 (Biological | |
| evaluation of medical devices - Part 6: Tests for local | |
| effects after implantation)) | Null to minimal reactivity |
| Material Mediated Pyrogenicity (per ISO 10993-11 | |
| (Biological evaluation of medical devices - Part 11: | |
| Tests for systemic toxicity)) | Non-pyrogenic |
Table 2: Implant Biocompatibility Testing Performed
3
| Acute/Subacute/Subchronic/Chronic Systemic
Toxicity, Genotoxicity and Carcinogenicity (addressed
through chemical characterization and toxicological
risk assessment per ISO 10993-18 (Biological
evaluation of medical devices - Part 18: Chemical
characterization of medical device materials within a
risk management process)/ISO 10993-17 (Biological
evaluation of medical devices - Part 17:
Establishment of allowable limits for leachable
substances) | Non-systemically
toxic/genotoxic/carcinogenic |
| --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------------------------------------------- |
|---|
A 26-week combined implantation and systemic toxicity rabbit study was conducted per ISO 10993-11:2017 in combination with assessment of local implantation effects per ISO 10993-6:2016. The test articles did not produce local or systemic toxicological effects.
For the reusable instruments, Table 3 shows the biocompatibility testing performed and the results, which were acceptable for instruments in limited contact with bone/tissue:
| Test Description | Result |
|---|---|
| Cytotoxicity (per ISO 10993-5 (Biological evaluation | |
| of medical devices - Part 5: Tests for in vitro | |
| cytotoxicity)) | Non-cytotoxic |
| Irritation (per ISO 10993-10 (Biological evaluation of | |
| medical devices - Part 10: Tests for irritation and skin | |
| sensitization) ) | Non-irritant |
| Sensitization (ISO 10993-10 (Biological evaluation of | |
| medical devices - Part 10: Tests for irritation and skin | |
| sensitization)) | Non-sensitizing |
| Acute Systemic Toxicity (per ISO 10993-11 | |
| (Biological evaluation of medical devices - Part 11: | |
| Tests for systemic toxicity)) | Non-toxic |
Table 3: Instrument Biocompatibility Testing Performed
STERILITY/PACKAGING AND SHELF-LIFE/PYROGENICITY
Sterility:
The MISHATM Knee System is a single-use device provided clean and sterile to the user. Gamma Sterilization of the device has been validated to provide a Sterility Assurance Level (SAL) of 10-6 based on the VDMax25 method as recommended by FDA Recognized Consensus Standard series ANSI/AAMI/ISO 11137-1 ("Sterilization of health care products - Radiation - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices")/-2 ("Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose").
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Packaging and Shelf-Life:
The MISHATM Knee System comes in three different packaging configurations. Each configuration includes an inner pouch, an outer pouch, and a protective carton. The material of the packaging is outlined in Table 4. The implants, screws and trials all share the "Small" configuration. The Targeting Kit and Fixation Kits share the "Large" configuration. In addition, the Targeting and Fixation Kits are packaged on a mounting card. The configuration of the Torque Limiting Driver is the same inner and outer pouch as the Targeting and Fixation kit with a protective carton of slightly different dimensions.
Table 4: Materials of Construction of Packaging System Components
| Inner and Outer Pouches | Protective Cartons | Mounting Cards |
|---|---|---|
| (b)(4) | ||
Non-clinical performance testing of the implant was used to assess the shelf-life of the device. The testing confirmed a 5-year shelf-life.
Pyrogenicity:
Bacterial endotoxins testing (BET) was performed to determine whether the MISHATM Knee System met pyrogen limit specifications. All tested devices passed with a reported value of ≤1 EU/device, meeting the recommended endotoxin limits per ANSI/AAMI ST72:2011 ("Bacterial endotoxins - Test methods, routine monitoring, and alternatives to batch testing").
MAGNETIC RESONANCE (MR) COMPATIBILITY
To support MR conditional labeling for the MISHATM Knee System, the following MR testing was conducted to evaluate device safety and compatibility:
- Magnetically Induced Displacement Force per ASTM F2052-15. "Standard Test . Method for Measurement of Magnetically Induced Displacement Force on Medical Devices in the Magnetic Resonance Environment";
- Magnetically Induced Torque per ASTM F2213-11, "Standard Test Method for . Measurement of Magnetically Induced Torque on Medical Devices in the Magnetic Resonance Environment";
- . Radiofrequency Induced Heating per ASTM F2182-11a, "Standard Test Method for Measurement of Radio Frequency Induced Heating Near Passive Implants During Magnetic Resonance Imaging"; and
5
- Imaging Artifacts per ASTM F2119-07 (Reapproved 2013), "Standard Test Method . for Evaluation of MR Image Artifacts from Passive Implants"
In magnetic field interaction tests, the MISHA™ Knee System implant showed a translation deflection angle of piral the maximum spatial gradient was (D)(4) (bx) and no torque. In image artifact testing, the maximum image artifact was measured for both spin echo and gradient echo pulse sequences in a 3.0 T MR scanner, and the maximum artifact size caused by the device extends approximately 37 mm from the implant when imaged with a gradient echo pulse sequence. In MRI-related heating testing, test results and in vivo modeling show that, the maximum temperature rise after 60 minutes continuous exposure is less than 6°C under the condition of the whole-body specific absorption rate (SAR) at 2 W/kg.
PERFORMANCE TESTING - BENCH
A summary of non-clinical mechanical performance evaluations is provided in Table 5:
| Test | Purpose | Method | Performance
Criteria | Results |
|--------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------|--------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Absorber Unloading
Capacity | Demonstrate the
minimum
compressive
resistance force
produced by the
absorber at its
implanted length. | (b)(4) | Demonstrate the
minimum
compressive
resistance force
produced by the
absorber at its
implanted length is ≥
15 lbs. | All specimens
exceeded the
performance criteria. |
| Durability, Wear,
and Corrosion
Resistance | Demonstrate the
implant functionality,
wear rate and
corrosion resistance in
a simulated in vivo
environment. | | Demonstrate the mean
polymeric and
metallic wear rate are
$≤$ 6.1 and $≤$ 0.004
$mm³$ per one million
cycles, respectively.
Demonstrate implant
materials (including | The mean polymeric
wear rate was 0.248
$mm³$ per one million
cycles.
The mean metallic
wear rate was 0.004
$mm³$ per one million
cycles. |
| Test | Purpose | Method | Performance
Criteria | Results |
| | | (b)(4) | (markings) are
corrosion resistant in
simulated in vivo
environments.
Demonstrate the
implant functionality
can be maintained for
$\ge$ 10 million
simulated gait cycles
at its implanted
length.
Functionality is
defined as: (1)
fixation of the bases
on the bones is
maintained, (2) the
device carries load
during low knee
flexion angles
representative of the
stance phase of gait,
and (3) device
components remain
contiguous and
mobile relative to one
another throughout
knee motion. | There was no
evidence of corrosion
after immersion in the
simulated in vivo
environment.
All test articles
remained functional
throughout testing
(10.3 million cycles). |
| Static Strength | Demonstrate the
implant will not
fracture or break
when subjected to
clinically relevant
loads. | | Demonstrate the
implant will not
fracture or break
when subjected to a
static compressive
load up to 60 lbs. | All articles survived a
static compressive
load of 65 lbs.
without any signs of
permanent
deformation or
damage of the
structural
components. |
Table 5: Summary of Non-clinical Mechanical Performance Evaluations
6
SUMMARY OF CLINICAL INFORMATION
Study Design
7
The sponsor conducted a prospective, multicenter clinical study comparing the Calypso Knee System (rebranded for this De Novo request) to the cohort of subjects treated with High Tibial Osteotomy (HTO) from a non-randomized trial ("GOAL" study-historical data from the Atlas IDE study). The Calypso Clinical Study was submitted to demonstrate the system's safety and effectiveness. Propensity Score (PS) methodology was employed to account for potential selection bias in the non-randomized comparison of the two groups and resulting in a PS Analysis set of 81 Calypso subjects and 81 Control (HTO) subjects in data through 24 months post-treatment. Clinical and radiographic follow-up visits occurred at 6 weeks, 3, 6, 12, 18 (N/A for HTO), and 24 months post-treatment. The Control (HTO) group completed follow-up visit at 24-months and the Calypso Knee group will continue to be followed through 5 years post-treatment.
Subject Demographics
The study population included male or female subjects aged 25 to 65 years for the Calypso Knee group and 25 to 80 years for the Control (HTO) group, with a diagnosis of medial knee osteoarthritis and knee pain with an overall Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥ 40 (scale 0-100), who have failed to improve after at least six months of conservative medical treatment.
A total of eighty-one (81) Calypso subjects and ninety-two (92) Control (HTO) subjects were enrolled. After PS matching, eight-one (81) Control (HTO) subjects were included in the study analysis. Table 6 presents a summary of the baseline characteristics for the Calypso Knee group and Control (HTO) group:
| Measure | Calypso | Control
(HTO) |
|-----------------------------------------------------------|------------------|------------------|
| N | 81 | 81 |
| Age, years | $51.2 \pm 7.71$ | $52.5 \pm 7.58$ |
| BMI, kg/m² | $28.4 \pm 3.44$ | $29.3 \pm 4.36$ |
| Duration (months) of OA
symptoms | $52.8 \pm 54.33$ | $35.3 \pm 50.69$ |
| KL Grade | $2.5 \pm 0.88$ | $2.8 \pm 0.98$ |
| WOMAC Pain | $60.4 \pm 12.37$ | $52.9 \pm 13.10$ |
| WOMAC Function | $59.9 \pm 15.93$ | $48.4 \pm 13.78$ |
| Debridement | 14.8% | 13.6% |
| Microfracture | 7.41% | 11.1% |
| Sex = Male % | 60.49% | 65.43% |
| Failed non-operative treatment
at/before Month 6 = Yes | 100% | 100% |
| Tourniquet Used | 82.7% | 75.3% |
| White | 98.8% | 100% |
| Non-Hispanic | 96.3% | 98% |
Table 6: Patient Baseline Characteristics
8
The age and BMI of the Calypso Knee group and Control (HTO) group are similar. The percentage of male subjects for the Calypso Knee group was about 5% lower compared to the Control (HTO) group and on average the Calypso Knee group had OA symptoms for 17.5 months longer compared to the Control (HTO) group. Despite the difference of the duration of osteoarthritis (OA) symptoms, the Kellgren and Lawrence (KL) Grade was similar for both groups. The baseline characteristics for the Calypso Knee and Control (HTO) group are comparable.
Primary Endpoint
The primary endpoint is a Composite Clinical Success (CCS) demonstrating noninferiority of the Calypso Knee System to HTO data from the GOAL study at 24 months post-treatment. A subject is considered a success at 24 months if all of the following components were met at 24 months:
- . Clinically significant improvement of at least 20% from baseline on the WOMAC pain questions in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee questionnaire with a change of ≥ 10 points
- . Clinically significant improvement of at least 20% from baseline on the WOMAC function questions in the KOOS Knee questionnaire with a change of ≥ 10 points
- . Freedom from the following device-related serious adverse events. or "Safety Endpoint Event" (SEE):
- · Deep infection requiring surgical intervention (Both arms)
- Damage to adjacent neurovascular or ligament structures necessitating o reconstruction (Both arms)
- o Non-union (HTO only)
- Maintenance of implant integrity as evaluated by radiographic assessment .
In addition to the four components, the protocol noted that a subject would also be a failure if a conversion to arthroplasty occurs through 24-months.
The sponsor conducted analysis of the primary endpoint with multiple imputation based on average treatment effect in the treated (ATT) for Month 24 clinical composite score. Using multiple imputation to account for missing data, the success rate was 83.5% for the Calvpso Knee group and 57.2% for the Control (HTO) group. Study success is based on a priori selected non-inferiority margin (δ) of -0.10. The success rate of the Calypso Knee group led the Control (HTO) group by 26.3% and the primary endpoint at 24 months was achieved in this study. Results are presented in Table 7 for all study subjects.
| Calypso | Control | |||||
|---|---|---|---|---|---|---|
| Outcome | N | n | % | N | n | % |
| Enrolled | 81 | 81 | 100.0% | 81 | 81 | 100.0% |
| No Endpoint Subsequent Surgical | ||||||
| Intervention | 81 | 80 | 98.8% | 81 | 80 | 98.8% |
| Table 7: Primary Endpoint Success at Month 24 Post-Treatment | |||
|---|---|---|---|
9
| Calypso | Control | |||||
|---|---|---|---|---|---|---|
| Outcome | N | n | % | N | n | % |
| WOMAC Pain endpoint responder | 72 | 69 | 95.8% | 58 | 51 | 87.9% |
| WOMAC Function endpoint | ||||||
| responder | 72 | 66 | 91.7% | 64 | 52 | 81.3% |
| No Safety Endpoint Event (CEC) | 81 | 77 | 95.1% | 81 | 76 | 93.8% |
| No Endpoint Implant Integrity Failure | 81 | 80 | 98.8% | 81 | 80 | 98.8% |
| Crude Observed | 74 | 62 | 83.8% | 63 | 41 | 65.1% |
| Completers | 74 | 62 | 83.8% | 63 | 34.3 | 54.4% |
| Multiple Imputation (MI) | 81 | 67.6 | 83.5% | 81 | 46.4 | 57.2% |
A tipping point analysis was conducted to analyze the sensitivity of missing data. Compared to the multiple imputation model, the tipping analysis does not require the same statistical assumptions as it analyzes every possible combination of the missing data. The results from the tipping analysis indicate that the non-inferiority study conclusion is robust and not impacted by the missing data.
Secondary Endpoints
The sponsor assessed the following five secondary endpoints to evaluate the superiority of the Calypso Knee System to the Control (HTO):
- . Time to full weight bearing
- Percent change from baseline to 3-months on the WOMAC pain in the KOOS . Knee Survey
- Percent change from baseline to 3-months on the WOMAC function in the KOOS . Knee Survey
- Percent change from baseline to 24-months on the WOMAC pain in the KOOS . Knee Survey
- Percent change from baseline to 24-months on the WOMAC function in the . KOOS Knee Survey
| Outcome | N | Calypso | N | Control | ||
|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | |||
| Time (days) to Full Weight Bearing | 81 | 13.4 | 10.12 | 77 | 58.0 | 39.91 |
| WOMAC Pain % Change from | ||||||
| Baseline at Month 3 | 81 | -55.5% | 29.3% | 72 | -33.4% | 35.8% |
| WOMAC Pain % Change from | ||||||
| Baseline at Month 24 | 72 | -76.0% | 28.2% | 58 | -72.5% | 33.0% |
| WOMAC Function % Change from | ||||||
| Baseline at Month 3 | 81 | -52.2% | 32.0% | 75 | -24.3% | 37.0% |
| WOMAC Function % Change from | ||||||
| Baseline at Month 24 | 72 | -73.9% | 29.6% | 64 | -67.1% | 35.8% |
The results for the secondary endpoint are outlined in Table 8 below:
10
The results from the study supported superiority of the Calypso Knee group compared to the Control (HTO) group in four of the five secondary endpoints. The one endpoint that the data did not support superiority for the Calypso Knee group was the WOMAC Pain % change from Baseline at Month 24.
Safety Analysis
There were no Unanticipated Adverse Device Effects as determined by the independent medical monitor for both the Calypso Knee group and Control (HTO) group. All deviceand procedure-related serious adverse events (SAEs) were considered expected complications. There were 11 removals (11/81. 13.58%) and 3 reoperations (3/81, 3.70%) for the Calypso Knee group and 61 removals (61/81, 75.31%), 1 revision (1/81, 1.23%), and 7 reoperations (7/81, 8.64%) for the Control (HTO) group. Note that the HTO plate can be electively removed after completing bone consolidation.
SAEs for the Calypso Knee group included 4 deep incisional surgical site infection (4/81, 4.94%) and 4 due to pain (4/81, 4.94%). Additional SAEs include nerve injury to a nerve resulting in motor or sensory symptoms, scar formation, discomfort, and cellulitis.
Pediatric Extrapolation
In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population.
LABELING
The labeling consists of the following: device description, indications for use, instructions for use including surgical steps (e.g., device selection and placement), principles of device operation, identification of device materials, contraindications, warnings, precautions, a list of potential adverse effects, and summary of the clinical data. Furthermore, the sterile packaging includes a shelf-life for the device. The labeling meets the requirements of 21 CFR 801.109 for prescription devices.
TRAINING
The surgical technique program consisted of slides that walk the surgeon through each step of the procedure to implant the MISHATM Knee System. The surgical technique training also provides insight on proper patient selection, surgical procedures, selection of appropriate implant size, instrumentation for implantation, indications for use of the device, contraindications, warnings, and precautions. A trained representative may be present to support surgical procedures.
11
RISKS TO HEALTH
The table below identifies the risks to health that may be associated with use of the medial knee implanted shock absorber and the measures necessary to mitigate these risks.
| Risks to Health | Mitigation Measures |
|---|---|
| Implant failure to improve | |
| osteoarthritis symptoms, including | |
| pain and discomfort | Clinical data |
| Non-clinical performance testing | |
| Training | |
| Pain and discomfort due to implant | Clinical data |
| Training | |
| Loss of implant integrity leading to | |
| loss of fixation and reoperation | Clinical data |
| Non-clinical performance testing | |
| Ligament or nerve injury resulting in | |
| motor and/or sensory damage | Clinical data |
| Training | |
| Scar formation | Clinical data |
| Training | |
| Infection | Sterilization validation |
| Reprocessing validation | |
| Shelf-life testing | |
| Pyrogenicity testing | |
| Labeling | |
| Adverse tissue reaction due to | |
| Device materials Fretting and corrosion Wear particulates | Biocompatibility evaluation |
| Non-clinical performance testing |
SPECIAL CONTROLS
In combination with the general controls of the FD&C Act, the medial knee implanted shock absorber is subject to the following special controls:
- Clinical data must demonstrate that the device performs as intended under anticipated (1) conditions of use and include the following:
- Evaluation of improvement of knee function and reduction of osteoarthritis (i) symptoms, including pain and function; and
- (ii) Evaluation of relevant adverse events.
- (2) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use and include the following:
- (i) Evaluation of the mechanical function and durability of the implant (including evaluation of absorber unloading capacity, fretting and corrosion, static strength, wear analysis, and fatigue testing); and
- (ii) Evaluation of worst-case device range of motion.
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- (3) The patient-contacting components of the device must be demonstrated to be biocompatible.
- Performance data must support the sterility and pyrogenicity of the device components (4) intended to be sterile.
- (5) Performance data must validate the reprocessing instructions for the reusable components of the device.
- (6) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf-life.
- (7) A training program must be included so that upon completion of the training program, the user can safely and successfully implant the device.
- (8) Labeling must include the following:
- Validated methods and instructions for reprocessing of any reusable components; (i) and
- (ii) A shelf-life.
BENEFIT-RISK DETERMINATION
BENEFITS:
-
- The clinical study demonstrates the MISHATM Knee System leads to clinically meaningful improvements in knee function and symptoms (e.g., reduction in pain) that are maintained over time to at least 24 months;
-
- Performance has been demonstrated to be non-inferior to High Tibial Osteotomy (HTO);
-
- The MISHATM Knee System secondary endpoint results (Return to Full Wait Bearing, Improved WOMAC Pain and Function Scores from baseline at 3 months, Improved WOMAC Function Scores from baseline at 24 months) support clinically meaningful, patient-valued benefits at a magnitude similar to, or numerically greater than, those observed with the Control HTO:
-
- The MISHATM Knee System does not require any bone cutting and maintains the natural joint surface compared to the Control HTO;
-
- Preserves the knee joint for future surgeries compared to the Control HTO.
RISKS:
-
- Adverse events of the index knee including pain, discomfort, unanticipated adverse device effects, subsequent surgical interventions, loosening and migration, and revision, including revision due to device wear, screw back out, or device failure;
-
- Adverse tissue reactions due to device materials, fretting and corrosion, and wear particulates:
-
- Infection:
-
- Loss of implant integrity;
-
- Ligament or nerve injury.
Based on the totality of the evidence, the MISHATM Knee System demonstrated a reasonable assurance of safety and effectiveness for the device for its intended use/indications for use. While there is a low degree of uncertainty in this finding due to the missing data from the control group in the clinical study and removal rate for the MISHA™ Knee System, the risks are not greater than HTO. To address the concerns of the longer-term safety and benefits of the MISHATM Knee System, the sponsor will be conducting a five (5) year 522 Postmarket
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Surveillance Study. In addition, the MISHA™ Knee System demonstrated improvement on the WOMAC pain and function scores over the course of the clinical study. In conclusion, the benefits of using the MISHATM Knee System for its intended use/indications for use outweigh the probable risks to health.
Patient Perspectives
Patient perspectives considered for the Misha Knee System during the review include:
- WOMAC Pain and Function Scores .
- KSS Satisfaction Scores .
Benefit/Risk Conclusion
In conclusion, given the available information above, for the following indication statement:
"The MISHA™ Knee System is indicated for patients with medial compartment knee osteoarthritis that have failed to find relief in surgical and/or non-surgical treatment modalities and are still experiencing pain that interferes with activities of daily living and are also unwilling to undergo or ineligible for total knee replacement due to age or absence of advanced osteoarthritis."
The probable benefits outweigh the probable risks for the MISHATM Knee System. The device provides benefits, and the risks can be mitigated by the general controls and the identified special controls.
CONCLUSION
The De Novo request for the MISHATM Knee System is granted and the device is classified as follows:
Product Code: OVV Device Type: Medial knee implanted shock absorber Regulation Number: 21 CFR 888.3610 Class: II