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CompletedNCT03485157Updated Dec 11, 2023Results posted

Micronized dHACM vs. Saline in the Treatment of Osteoarthritis of the Knee

A Phase 2 interventional study of Micronized dHACM and Saline in Knee Osteoarthritis, sponsored by MiMedx Group, Inc.. Completed at 17 sites in United States. Open to participants aged 21 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-12-11.

Sponsored by MiMedx Group, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
447
Allocation
Randomized
Ages
21 Years to 80 Years
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Knee Osteoarthritis
03

Who can participate

Ages eligible
21 Years to 80 Years
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
447 participants (actual)

Study arms

  • Experimental
    Micronized dHACM

    Injection of micronized dHACM

    Biological: Micronized dHACM

  • Placebo comparator
    Saline

    Injection of 0.9% Sodium Chloride Injection, USP

    Drug: Saline

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

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

Secondary outcomes

  1. 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

  2. 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

Other outcomes

  1. 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

  2. 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

  3. 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

  4. 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

06

Results

Posted Dec 11, 2023

Participant flow

Double Blind Phase
Participant flow — Double Blind Phase
MilestoneMicronized dHACMSaline
Started223224
Completed208203
Not completed1521
Withdrew: Lost to follow-up44
Withdrew: Adverse event21
Withdrew: Withdrawal by subject69
Withdrew: Removal by pi37
Open Label Phase
Participant flow — Open Label Phase
MilestoneMicronized dHACMSaline
Started108109
Completed104104
Not completed45
Withdrew: Lost to follow-up12
Withdrew: Adverse event01
Withdrew: Withdrawal by subject12
Withdrew: Removal by pi20

Outcome measures

PrimaryPrimary 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
Reported as:
Mean · score on a scale
Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days
score on a scaleMicronized dHACMSaline
Value32.8 ± 26.3934.1 ± 26.40
Change from baseline-35.1 ± 26.72-34.2 ± 26.87
PrimaryPrimary 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
Reported as:
Mean · score on a scale
Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days
score on a scaleMicronized dHACMSaline
Value26.9 ± 18.4328.8 ± 18.98
Change from baseline-20.6 ± 18.16-19.6 ± 17.99
PrimaryPrimary 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
Reported as:
Count of participants · Participants
Primary Safety Endpoint: Number of Participants With Adverse Events (AEs)
ParticipantsMicronized dHACMSaline
Primary Safety Endpoint: Number of Participants With Adverse Events (AEs)123120
PrimaryPrimary 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
Reported as:
Count of participants · Participants
Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs)
ParticipantsMicronized dHACMSaline
Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs)1112
PrimaryPrimary 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
Reported as:
Count of participants · Participants
Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events
ParticipantsMicronized dHACMSaline
Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events1616
SecondarySecondary 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
Reported as:
Mean · score on a scale
Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days
score on a scaleMicronized dHACMSaline
Value31.1 ± 26.9832.2 ± 27.35
Change From Baseline-36.9 ± 28.51-36.1 ± 27.94
SecondarySecondary 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
Reported as:
Mean · score on a scale
Secondary Endpoint:Change From Baseline in WOMAC at 180 Days
score on a scaleMicronized dHACMSaline
Value26.0 ± 19.4527.6 ± 19.63
Change From Baseline-21.6 ± 20.91-20.8 ± 20.67
Other pre-specifiedExploratory 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

Results for this outcome have not been posted.

Other pre-specifiedExploratory 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

Results for this outcome have not been posted.

Other pre-specifiedExploratory 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

Results for this outcome have not been posted.

Other pre-specifiedExploratory 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

Results for this outcome have not been posted.

Adverse events

Collected over Adverse Events were collects for 1 year in the double blinded study and 6 months in the Open Label Study.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Micronized dHACM0/223 (0%)11/223 (4.9%)123/223 (55.2%)
Saline0/224 (0%)12/224 (5.4%)120/224 (53.6%)
Open-Label Micronized dHACM0/217 (0%)5/217 (2.3%)94/217 (43.3%)
Most frequent serious events
Showing 10 of 30
Most frequent serious events
EventMicronized dHACMSalineOpen-Label Micronized dHACM
ArthralgiaMusculoskeletal and connective tissue disorders0/2232/2240/217
OsteoarthritisMusculoskeletal and connective tissue disorders0/2231/2241/217
FallInjury, poisoning and procedural complications0/2230/2241/217
Hand fractureInjury, poisoning and procedural complications0/2230/2241/217
OverdoseInjury, poisoning and procedural complications0/2230/2241/217
Road traffic accidentInjury, poisoning and procedural complications0/2230/2241/217
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders1/2230/2240/217
DiverticulitisInfections and infestations1/2230/2240/217
Staphylococcal infectionInfections and infestations1/2230/2240/217
Coronary artery occlusionCardiac disorders1/2230/2240/217
Most frequent other events
Showing 10 of 188
Most frequent other events
EventMicronized dHACMSalineOpen-Label Micronized dHACM
ArthralgiaMusculoskeletal and connective tissue disorders47/22349/22429/217
Injection site joint painGeneral disorders14/2232/22421/217
OsteoarthritisMusculoskeletal and connective tissue disorders7/22311/2245/217
Back painMusculoskeletal and connective tissue disorders4/22310/2242/217
Injection site joint swellingGeneral disorders3/2230/2249/217
Joint swellingMusculoskeletal and connective tissue disorders8/2237/2247/217
Oedema peripheralGeneral disorders7/2232/2243/217
Pain in extremityMusculoskeletal and connective tissue disorders6/2236/2241/217
Ligament sprainInjury, poisoning and procedural complications2/2232/2245/217
Joint effusionMusculoskeletal and connective tissue disorders5/2234/2241/217

Baseline characteristics

Demographic and baseline characteristics of subjects in the ITT Set.

Age, Continuous
Age, Continuous(years)Micronized dHACMSalineTotal
Mean57.89 ± 10.61958.45 ± 11.29458.17 ± 10.954
Sex: Female, Male
Sex: Female, Male(Participants)Micronized dHACMSalineTotal
Female120140260
Male10384187
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Micronized dHACMSalineTotal
Hispanic or Latino121224
Not Hispanic or Latino211212423
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Micronized dHACMSalineTotal
American Indian or Alaska Native022
Asian437
Native Hawaiian or Other Pacific Islander011
Black or African American241943
White193195388
More than one race000
Unknown or Not Reported246
Height (in)
Height (in)(Inches)Micronized dHACMSalineTotal
Mean67.17 ± 4.11466.72 ± 3.74866.94 ± 3.937
Weight
Weight(lbs)Micronized dHACMSalineTotal
Mean187.22 ± 39.629185.12 ± 40.305186.17 ± 39.938
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)Micronized dHACMSalineTotal
Mean29.74 ± 4.91929.81 ± 5.27929.77 ± 5.097
07

Study locations

17 sites
  • Central Research Associates, Inc
    Birmingham, Alabama 35205, United States
  • Fiel Family and Sports Medicine
    Tempe, Arizona 85283, United States
  • Horizon Clinical Research
    La Mesa, California 91942, United States
  • UConn Health
    Farmington, Connecticut 06030, United States
  • Bone & Joint Inst. at Hartford Hospital
    Hartford, Connecticut 06106, United States
  • Gulfcoast Research Institute
    Sarasota, Florida 34232, United States
  • Paragon Sports Medicine
    Atlanta, Georgia 30327, United States
  • Hinsdale Orthopedics
    Hinsdale, Illinois 60521, United States
  • Arthritis Care Specialist of Maryland
    Columbia, Maryland 21046, United States
  • MedSport
    Ann Arbor, Michigan 48106, United States
  • Weill Cornell Medicine
    New York, New York 10065, United States
  • Wake Reseach
    Durham, North Carolina 27704, United States
  • Wake Research
    Raleigh, North Carolina 27612, United States
  • University Orthopedics Center
    Altoona, Pennsylvania 16602, United States
  • University Orthopedics Center
    State College, Pennsylvania 16801, United States
  • SAMMC
    Fort Sam Houston, Texas 78234, United States
  • Ortho Virginia
    Richmond, Virginia 23294, United States
08

References and documents

Study documents

  • Study protocol · Jan 31, 2020
  • Statistical analysis plan · Jun 24, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03485157
Lead sponsor
MiMedx Group, Inc.
Responsible party
Sponsor
First posted
Apr 2, 2018
Start date
Mar 27, 2018
Primary completion
Apr 19, 2022
Completion
Apr 19, 2022
Results posted
Dec 11, 2023
Last update
Dec 11, 2023

Study contacts

Alfred C Gellhorn, MD
principal investigator · Esprit R&D Associate GSK

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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