Knee Osteoarthritis
Conditions
Brief summary
The purpose of this study is to determine the safety and effectiveness of micronized dehydrated human amnion chorion membrane as compared to the 0.9% Sodium Chloride Injection, USP placebo control for the treatment of knee osteoarthritis
Detailed description
Each subject will receive 1 injection (micronized dHACM or placebo) and be evaluated for efficacy and safety during a 12-month observation period. A second injection (open-label access to micronized dHACM) will be offered to all subjects at the 180-day, 270-day, and 365-day time points, it may only be used once. Blinding for the first injection treatment allocation will be maintained until the end of the study. Subjects who receive the open-label access treatment will continue to be followed for 180 days after this second injection, regardless of the time at which treatment was received.
Interventions
BIOLOGICALMicronized dHACM
Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP
DRUGSaline
Injection of 1 mL 0.9% Sodium Chloride, USP
Sponsors
MiMedx Group, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 21 and ≤ 80 years 2. Subject has a diagnosis of osteoarthritis (OA) defined as Grade 1 to 3 on the Kellgren Lawrence grading scale 3. Subject is willing and able provide informed consent and participate in all procedures and follow-up evaluations necessary to complete the study 4. Subject must have a VAS pain scale greater than 45
Exclusion criteria
1. Subject has a diagnosis of osteoarthritis (OA) defined as Grade 4 on the Kellgren Lawrence grading scale 2. BMI greater than 40 kg/m\^2 3. Subject has active infection at the injection site 4. Symptomatic OA of the contralateral knee or of either hip that is not responsive to acetaminophen (Tylenol®) and requires other therapy. 5. Subject has rheumatoid arthritis, psoriatic arthritis, or have been diagnosed with any other disorders that is the primary source of their knee pain, including but not limited to: osteonecrosis, radiculopathy, bursitis, tendinitis, tumor, cancer 6. Subject has documented history of gout or pseudo-gout 7. Subject has autoimmune disease or a known history of having Acquired Immunodeficiency Syndromes (AIDS) or HIV 8. Subject has received any of the following to the target knee: 1. Intra-articular hyaluronic acid (HA) injection within 12 weeks prior to screening 2. Steroid or platelet rich plasma (PRP) injection within 12 weeks prior to screening 3. Has had or is planning to have major surgery or arthroscopy in the target knee within 26 weeks of treatment 4. History of a total knee arthroplasty 9. Subject has used an investigational drug, device or biologic within 12 weeks prior to treatment 10. Subject has a history of immunosuppressive or chemotherapy in the last 5 years 11. Subject has had prior radiation at the site 12. Subject is currently taking anticoagulant therapy (excluding Plavix or Aspirin) 13. Subject is pregnant or plans to become pregnant within 365 days of treatment 14. Subject has any significant medical condition that, in the opinion of the Investigator, would interfere with protocol evaluation and participation 15. Subject is a worker's compensation patient 16. Subject is a prisoner
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days | 90 days | Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: * Pain (5 questions) * Stiffness (2 questions) * Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days | 90 days | Visual Analog Scale (VAS): 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain |
| Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs) | 365 days | Number of Participants with At Least 1 Serious Treatment Emergent Adverse Event (TEAE) Reported |
| Primary Safety Endpoint: Number of Participants With Adverse Events (AEs) | 365 days | Number of Participants with At Least 1 Treatment Emergent Adverse Event (TEAE) Reported |
| Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events | 365 days | Number of Participants with At Least 1 Unanticipated Treatment Emergent Adverse Event (TEAE) Reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Endpoint:Change From Baseline in WOMAC at 180 Days | 180 days | Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: * Pain (5 questions) * Stiffness (2 questions) * Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days | 180 days | Visual Analog Scale (VAS) : 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Endpoint: Change From Baseline in the Visual Analog Scale (VAS) for Pain at 270, and 365 Days | Up to 365 days | VAS: 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain |
| Exploratory Endpoint: Change From Baseline in the KOOS Scores at 90, 180, 270, and 365 Days | Up to 365 days | Knee Injury and Osteoarthritis Outcome Score (KOOS): 5 subscales scored on a 5 point scale where the final score is summed and transformed into a 100 point scale with a higher score representing no disability and a lower score representing extreme disability |
| Exploratory Endpoint: Change From Baseline in the Visual Analog Scale (VAS) for Satisfaction at 90, 180, 270 and 365 Days | Up to 365 days | VAS: 0 to 100 mm horizontal visual analog scale with a higher score indicating greater satisfaction |
| Exploratory Endpoint: Change From Baseline in the WOMAC Scores at 270 and 365 Days | Up to 365 days | Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: * Pain (5 questions) * Stiffness (2 questions) * Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
Countries
United States
Participant flow
Pre-assignment details
Screening visit occurred after enrollment and could possibly be the same day as randomization/treatment.
Participants by arm
| Arm | Count |
|---|---|
| Micronized dHACM Injection of micronized dHACM
Micronized dHACM: Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP | 223 |
| Saline Injection of 0.9% Sodium Chloride Injection, USP
Saline: Injection of 1 mL 0.9% Sodium Chloride, USP | 224 |
| Total | 447 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double Blind Phase | Adverse Event | 2 | 1 |
| Double Blind Phase | Lost to Follow-up | 4 | 4 |
| Double Blind Phase | Removal by PI | 3 | 7 |
| Double Blind Phase | Withdrawal by Subject | 6 | 9 |
| Open Label Phase | Adverse Event | 0 | 1 |
| Open Label Phase | Lost to Follow-up | 1 | 2 |
| Open Label Phase | Removal by PI | 2 | 0 |
| Open Label Phase | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Micronized dHACM | Total | Saline |
|---|---|---|---|
| Age, Continuous | 57.89 years STANDARD_DEVIATION 10.619 | 58.17 years STANDARD_DEVIATION 10.954 | 58.45 years STANDARD_DEVIATION 11.294 |
| Body Mass Index (BMI) | 29.74 kg/m^2 STANDARD_DEVIATION 4.919 | 29.77 kg/m^2 STANDARD_DEVIATION 5.097 | 29.81 kg/m^2 STANDARD_DEVIATION 5.279 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 211 Participants | 423 Participants | 212 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height (in) | 67.17 Inches STANDARD_DEVIATION 4.114 | 66.94 Inches STANDARD_DEVIATION 3.937 | 66.72 Inches STANDARD_DEVIATION 3.748 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 43 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 193 Participants | 388 Participants | 195 Participants |
| Sex: Female, Male Female | 120 Participants | 260 Participants | 140 Participants |
| Sex: Female, Male Male | 103 Participants | 187 Participants | 84 Participants |
| Weight | 187.22 lbs STANDARD_DEVIATION 39.629 | 186.17 lbs STANDARD_DEVIATION 39.938 | 185.12 lbs STANDARD_DEVIATION 40.305 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 223 | 0 / 224 | 0 / 217 |
| other Total, other adverse events | 123 / 223 | 120 / 224 | 94 / 217 |
| serious Total, serious adverse events | 11 / 223 | 12 / 224 | 5 / 217 |
Outcome results
Primary
Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days
Visual Analog Scale (VAS): 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain
Time frame: 90 days
Population: Population: Intent To Treat Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Micronized dHACM | Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days | Value | 32.8 score on a scale | Standard Deviation 26.39 |
| Micronized dHACM | Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days | Change from baseline | -35.1 score on a scale | Standard Deviation 26.72 |
| Saline | Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days | Change from baseline | -34.2 score on a scale | Standard Deviation 26.87 |
| Saline | Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days | Value | 34.1 score on a scale | Standard Deviation 26.4 |
Primary
Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days
Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: * Pain (5 questions) * Stiffness (2 questions) * Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 90 days
Population: Population: Intent To Treat Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Micronized dHACM | Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days | Value | 26.9 score on a scale | Standard Deviation 18.43 |
| Micronized dHACM | Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days | Change from baseline | -20.6 score on a scale | Standard Deviation 18.16 |
| Saline | Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days | Value | 28.8 score on a scale | Standard Deviation 18.98 |
| Saline | Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days | Change from baseline | -19.6 score on a scale | Standard Deviation 17.99 |
Primary
Primary Safety Endpoint: Number of Participants With Adverse Events (AEs)
Number of Participants with At Least 1 Treatment Emergent Adverse Event (TEAE) Reported
Time frame: 365 days
Population: Subjects with at least 1 Treatment Emergent Adverse Event reported
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Micronized dHACM | Primary Safety Endpoint: Number of Participants With Adverse Events (AEs) | 123 Participants |
| Saline | Primary Safety Endpoint: Number of Participants With Adverse Events (AEs) | 120 Participants |
Primary
Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs)
Number of Participants with At Least 1 Serious Treatment Emergent Adverse Event (TEAE) Reported
Time frame: 365 days
Population: Subjects reporting Serious Adverse Events
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Micronized dHACM | Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs) | 11 Participants |
| Saline | Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs) | 12 Participants |
Primary
Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events
Number of Participants with At Least 1 Unanticipated Treatment Emergent Adverse Event (TEAE) Reported
Time frame: 365 days
Population: Subjects reporting Unanticipated Treatment Emergent Adverse Events
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Micronized dHACM | Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events | 16 Participants |
| Saline | Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events | 16 Participants |
Secondary
Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days
Visual Analog Scale (VAS) : 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain
Time frame: 180 days
Population: Population: Intent To Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Micronized dHACM | Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days | Value | 31.1 score on a scale | Standard Deviation 26.98 |
| Micronized dHACM | Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days | Change From Baseline | -36.9 score on a scale | Standard Deviation 28.51 |
| Saline | Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days | Value | 32.2 score on a scale | Standard Deviation 27.35 |
| Saline | Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days | Change From Baseline | -36.1 score on a scale | Standard Deviation 27.94 |
Secondary
Secondary Endpoint:Change From Baseline in WOMAC at 180 Days
Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: * Pain (5 questions) * Stiffness (2 questions) * Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 180 days
Population: Population: Intent To Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Micronized dHACM | Secondary Endpoint:Change From Baseline in WOMAC at 180 Days | Value | 26.0 score on a scale | Standard Deviation 19.45 |
| Micronized dHACM | Secondary Endpoint:Change From Baseline in WOMAC at 180 Days | Change From Baseline | -21.6 score on a scale | Standard Deviation 20.91 |
| Saline | Secondary Endpoint:Change From Baseline in WOMAC at 180 Days | Value | 27.6 score on a scale | Standard Deviation 19.63 |
| Saline | Secondary Endpoint:Change From Baseline in WOMAC at 180 Days | Change From Baseline | -20.8 score on a scale | Standard Deviation 20.67 |
Other Pre-specified
Exploratory Endpoint: Change From Baseline in the KOOS Scores at 90, 180, 270, and 365 Days
Knee Injury and Osteoarthritis Outcome Score (KOOS): 5 subscales scored on a 5 point scale where the final score is summed and transformed into a 100 point scale with a higher score representing no disability and a lower score representing extreme disability
Time frame: Up to 365 days
Other Pre-specified
Exploratory Endpoint: Change From Baseline in the Visual Analog Scale (VAS) for Pain at 270, and 365 Days
VAS: 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain
Time frame: Up to 365 days
Other Pre-specified
Exploratory Endpoint: Change From Baseline in the Visual Analog Scale (VAS) for Satisfaction at 90, 180, 270 and 365 Days
VAS: 0 to 100 mm horizontal visual analog scale with a higher score indicating greater satisfaction
Time frame: Up to 365 days
Other Pre-specified
Exploratory Endpoint: Change From Baseline in the WOMAC Scores at 270 and 365 Days
Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: * Pain (5 questions) * Stiffness (2 questions) * Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: Up to 365 days