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

A Phase 2B, Prospective, Double-blinded, Randomized Controlled Trial of the Micronized Dehydrated Human Amnion Chorion Membrane Injection as Compared to Saline Placebo Injection in the Treatment of Osteoarthritis of the Knee

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

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Saline; Biological: Micronized dHACM

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.

• Study Type: Interventional
• Enrollment (Actual): 447
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Micronized dHACM; Injection of micronized dHACM	Biological: Micronized dHACM; Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP
Placebo Comparator: Saline; Injection of 0.9% Sodium Chloride Injection, USP	Drug: Saline; Injection of 1 mL 0.9% Sodium Chloride, USP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	90 days
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.	90 days
Primary Safety Endpoint: Number of Participants With Adverse Events (AEs)	Number of Participants with At Least 1 Treatment Emergent Adverse Event (TEAE) Reported	365 days
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	365 days
Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events	Number of Participants with At Least 1 Unanticipated Treatment Emergent Adverse Event (TEAE) Reported	365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	180 days
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.	180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 365 days
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.	Up to 365 days
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	Up to 365 days
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	Up to 365 days

Collaborators and Investigators

• Sponsor: MiMedx Group, Inc.
• Investigators: Principal Investigator: Alfred C Gellhorn, MD, Esprit R&D Associate GSK

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2018
• Primary Completion (Actual): April 19, 2022
• Study Completion (Actual): April 19, 2022

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Actual): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: AIOA001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No