Efficacy of Amniotic Suspension Allograft in Patients With Osteoarthritis of the Knee

A Phase 3 Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy of Amniotic Suspension Allograft (ASA) in Patients With Osteoarthritis of the Knee

This study is being conducted to evaluate the efficacy and safety of ASA compared to placebo in the management of osteoarthritis (OA) symptoms of the knee.

Study Overview

• Status: Active, not recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: Amniotic Suspension Allograft; Drug: Placebo

Detailed Description

This is a prospective, multicenter, randomized, double-blind, placebo-controlled Phase 3 study of ASA in patients with OA of the knee. Initially, 474 subjects are planned for inclusion in this study using a group sequential design with two interim analyses and a final analysis. Sample size re-estimation is planned at the second interim analysis. Based on conditional power, the maximum sample size may be increased to up to 700 patients. Patients will be randomly assigned in a 1:1 ratio to receive a single intra-articular (IA) injection of 2 mL of ASA (plus 2 mL of normal saline) or 4 mL of normal saline.

Patients will be screened after informed consent is obtained. Eligible patients will be randomized to receive a single IA injection on Day 1. They will have serial assessments of knee pain, function, and symptoms scores, as well as safety assessments for up to 52 weeks after administration of the study drug.

The planned sequence and maximum duration of the study periods will be as follows:

• Screening: 2 weeks
• Treatment: 1 day
• Follow-up: 52 weeks

The maximum treatment duration for each patient is 1 day.

The maximum study duration for each patient is 54 weeks.

Efficacy will be assessed via Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder rates.

Safety will be assessed via monitoring of adverse events (AEs), safety laboratory testing, vital signs, physical examination, and concomitant medication use.

An independent data monitoring committee (DMC) with a defined charter will review study data and make preliminary decisions relative to interim analyses.

The assessments that are used in this study are standard, and are generally recognized as reliable, accurate, and relevant.

No pediatric patients will be included as OA of the knee is an age-related disorder and rarely occurs in patients under the age of 18 years. The sponsor plans to submit a waiver for studies in all pediatric age subgroups.

• Study Type: Interventional
• Enrollment (Estimated): 474
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Brett Madden; Phone Number: (781) 615-1876; Email: bmadden@organo.com
• Study Contact Backup: Name: Cristina Seltzer; Email: cseltzer@organo.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics
    • Mobile, Alabama, United States, 36608
      • AMR Mobile
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis & Rheumatology Research
    • Tempe, Arizona, United States, 85283
      • Fiel Family & Sports Medicine/ CCT Research
    • Tucson, Arizona, United States, 85704
      • Arizona Arthritis & Rheumatology Research
  • California
    • El Cajon, California, United States, 92020
      • Tri West Research Associates
    • La Mesa, California, United States, 91942
      • Horizon Clinical Research Center
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles
    • Los Angeles, California, United States, 90036
      • Actca, A Member of the Allliance Inc.
    • Redwood City, California, United States, 94063
      • Stanford Medicine
    • Sacramento, California, United States, 95186
      • University of California at Davis
  • Florida
    • Aventura, Florida, United States, 33180
      • AARDS Research, Inc.
    • Sarasota, Florida, United States, 34232
      • Gulfcoast Research Institute
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Pinnacle Trials, Inc.
  • Idaho
    • Boise, Idaho, United States, 83713
      • Injury Care Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60607
      • Chicago Clinical Research Institute Inc
    • Oak Brook, Illinois, United States, 60523
      • Affinity Health
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Hagerstown, Maryland, United States, 21740
      • Klein & Associates, MD, PA
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Nebraska
    • Fremont, Nebraska, United States, 68025
      • Methodist Physicians Clinic/ CCT Researc
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
    • New York, New York, United States, 10075
      • Lenox Hill Hospital (Northwell Health)
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • M3 Emerging Medical Research, LLC
    • Morehead City, North Carolina, United States, 28557
      • Moore Orthopedics and Sports Medicine
    • Raleigh, North Carolina, United States, 27612
      • M3 Emerging Medical Research, LLC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Altoona, Pennsylvania, United States, 16602
      • University Orthopedics Center
    • State College, Pennsylvania, United States, 16801
      • University Orthopedic Center
  • South Carolina
    • Greenville, South Carolina, United States, 29501
      • PCPMG Clinical Research Unit, LLC
    • North Charleston, South Carolina, United States, 29406
      • Coastal Carolina Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Affinity Health
  • Texas
    • Burleson, Texas, United States, 76028
      • Cedar Health Research, LLC
  • Virginia
    • Danville, Virginia, United States, 24541
      • Spectrum Medical, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females 18 years of age or older
2. Diagnosis of OA of the knee by a combination of clinical and radiographic findings
3. OA of the knee with Kellgren and Lawrence radiographic classification (Grade 2-4 inclusive) confirmed by posterior-anterior, weight-bearing, fixed flexion radiography with 10° caudal beam angulation. A specially designed positioning frame will be used to standardize the positioning for image acquisition.
4. Patients who have failed to adequately respond for at least 6 months to at least 2 OA therapies that include conservative, non-pharmacological therapy and simple analgesics (e.g., acetaminophen); nonsteroidal anti-inflammatory drugs (NSAIDS); avoidance of activities that cause joint pain; exercise; weight loss; physical therapy; and removal of excess fluid from the knee
5. Overall pain score over the previous 7 days of 11 or more on the WOMAC Pain scale.
6. Body mass index (BMI) < 40 kg/m²
7. If female, must be postmenopausal (for at least 2 years), surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), sexually abstinent, or willing and able to use 2 methods of contraception from Day 1 through 12 months after treatment
8. Males who are not surgically sterile (vasectomy) for at least 6 months prior to screening must confirm their willingness to use adequate methods of contraception from Day 1 through 12 months after treatment
9. Willing to agree not to use illicit drugs during the study, and to have illicit drug testing at screening and at later time points, if illicit drug use is suspected during the study
10. Able to comply with study requirements and complete the full sequence of protocol-related procedures and evaluations, including post-hospitalization, out-patient, and follow-up visits
11. Able to understand and provide written informed consent

Exclusion Criteria:

1. Use of pain medication (including NSAIDs and cannabidiol [CBD] oil) less than 15 days before treatment (acetaminophen allowed)
2. Regular use of anticoagulants
3. Symptoms of locking, intermittent block to range of motion, or loose body sensation that could indicate meniscal displacement or an IA loose body
4. Corticosteroid injection into the index knee within 3 months prior to screening
5. Viscosupplement (e.g., hyaluronic acid [HA]) injection, platelet-rich plasma injection, bone marrow aspirate (BMA) or bone marrow aspiration concentrate (BMAC), placental-derived tissue/cells, adipose tissue, or any other autologous or allogeneic product into the index knee within 6 months prior to screening
6. Patients with known hypersensitivity reactions to ASA or any of its constituents (e.g., HA, dimethyl sulfoxide [DMSO])
7. Knee surgery on the index knee within 12 months prior to screening and/or planned knee surgery during the study
8. Knee surgery on the contralateral knee within 6 months prior to screening and/or planned knee surgery during the study
9. Acute index knee trauma within 3 months prior to screening
10. Knee effusion requiring aspiration of the index or contralateral knee within 3 months prior to screening
11. Contralateral knee pain ≥ 4 on the WOMAC Pain scale on most days during the past week.
12. Current therapy with any immunosuppressive therapy, including corticosteroids (> 5 mg/day of prednisone)
13. Clinically significant findings on the screening laboratory tests or physical examination that are not specific to OA of the knee and may interfere with study conduct or interpretation of data or increase patient risk
14. Clinically significant intercurrent illness, medical condition, non-knee pain, or medical history (including neurological or mental illness, human immunodeficiency virus, fibromyalgia, complex regional pain syndrome, or any active infection, including hepatitis B or C) that could jeopardize the patient safety, limit participation, or compromise interpretation of data derived from the patient
15. Active alcohol or substance use disorder, or any other reason that would make it unlikely for the patient to comply with study procedures
16. Females who are pregnant (positive pregnancy test at screening or prior to treatment) or lactating
17. Participation in another clinical trial within the 30 days (or 5 half-lives of the investigational compound, whichever is longer) before screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASA; Participants receive a single IA injection of 2 mL of ASA (plus 2 mL of normal saline)	Biological: Amniotic Suspension Allograft; This investigational product is a cryopreserved product derived from human amnion and cells from the amniotic fluid.
Placebo Comparator: Placebo; Participants receive a single IA injection of 4 mL of normal saline	Drug: Placebo; Matching placebo is 0.9% normal saline: 4 mL to be injected IA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in change from baseline in WOMAC Pain scale at 6 months between ASA- and placebo-treated patients	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference between changes from baseline for ASA- and placebo- treated patients in WOMAC Function at 6 months	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 26
The difference between changes from baseline for ASA- and placebo-treated patients in the OMERACT-OARSI responder rate at 6 months	Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. (OMERACT-OARSI) Responders are defined as participants with high improvement in pain or function.	Baseline to Week 26
The difference between changes from baseline for ASA- and placebo-treated patients in WOMAC Pain at 3 months	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 12
The difference between changes from baseline for ASA- and placebo- treated patients in non-inferiority of WOMAC Function at 3 months	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 12
The difference between changes from baseline for ASA- and placebo-treated patients in the OMERACT-OARSI responder rate at 3 months	Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. (OMERACT-OARSI) Responders are defined as participants with high improvement in pain or function.	Baseline to Week 12
The difference between changes from baseline for ASA- and placebo-treated patients in the WOMAC Total at 6 months	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 26
The difference between ASA- and placebo-treated patients in the WOMAC Stiffness at 6 months	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 26
The difference between changes from baseline for ASA- and placebo- treated patients in the WOMAC Total at 3 months	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 12
The difference between changes from baseline for ASA- and placebo-treated patients in the WOMAC Stiffness at 3 months	The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	Baseline to Week 12
Incidence of adverse events (AEs)	An AE is any untoward medical occurrence in a clinical study patient administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. This includes any occurrence that is new in onset or aggravated in severity or frequency from the baseline condition, or abnormal result of diagnostic procedures, including clinical laboratory test abnormalities.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Organogenesis
• Collaborators: Premier Research Group plc

Publications and helpful links

Helpful Links

• Farr J, et al. A randomized controlled single-blind study demonstrating superiority of ASA injection over hyaluronic acid and saline control for modification of knee OA symptoms. J Knee Surg. 2019; https://doi.org/10.1055/s-0039-1696672.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Actual): July 30, 2023
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Arthritis; Osteoarthritis; Knee; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 19 OA 001 ASA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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