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

Sponsor

Organogenesis (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04636229

Collaborator

Premier Research Group plc (Industry)

474

Enrollment

Locations

Arms

35.5

Anticipated Duration (Months)

11.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	Biological: Amniotic Suspension Allograft Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

474 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a prospective, multicenter, randomized, double-blind, placebo-controlled study of ASA in patients with OA of the knee. Patients will be randomly assigned in a 1:1 ratio to receive a single IA injection of 2 mL of ASA (plus 2 mL of normal saline) or 4 mL of normal saline.This is a prospective, multicenter, randomized, double-blind, placebo-controlled study of ASA in patients with OA of the knee. Patients will be randomly assigned in a 1:1 ratio to receive a single IA injection of 2 mL of ASA (plus 2 mL of normal saline) or 4 mL of normal saline.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

All clinic staff who may be involved in making assessments of safety will be blinded to treatment assignment.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 14, 2020

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

The difference in change from baseline in WOMAC Pain scale at 6 months between ASA- and placebo-treated patients [Baseline to Week 26]
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.

Secondary Outcome Measures

The difference between changes from baseline for ASA- and placebo- treated patients in WOMAC Function at 6 months [Baseline to Week 26]
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.
The difference between changes from baseline for ASA- and placebo-treated patients in the OMERACT-OARSI responder rate at 6 months [Baseline to Week 26]
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.
The difference between changes from baseline for ASA- and placebo-treated patients in WOMAC Pain at 3 months [Baseline to Week 12]
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.
The difference between changes from baseline for ASA- and placebo- treated patients in non-inferiority of WOMAC Function at 3 months [Baseline to Week 12]
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.
The difference between changes from baseline for ASA- and placebo-treated patients in the OMERACT-OARSI responder rate at 3 months [Baseline to Week 12]
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.
The difference between changes from baseline for ASA- and placebo-treated patients in the WOMAC Total at 6 months [Baseline to Week 26]
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.
The difference between ASA- and placebo-treated patients in the WOMAC Stiffness at 6 months [Baseline to Week 26]
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.
The difference between changes from baseline for ASA- and placebo- treated patients in the WOMAC Total at 3 months [Baseline to Week 12]
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.
The difference between changes from baseline for ASA- and placebo-treated patients in the WOMAC Stiffness at 3 months [Baseline to Week 12]
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.
Incidence of adverse events (AEs) [Baseline to Week 52]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females 18 years of age or older
Diagnosis of OA of the knee by a combination of clinical and radiographic findings
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.
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
Overall pain score over the previous 7 days of 11 or more on the WOMAC Pain scale.
Body mass index (BMI) < 40 kg/m²
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
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
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
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
Able to understand and provide written informed consent

Exclusion Criteria:

Use of pain medication (including NSAIDs and cannabidiol [CBD] oil) less than 15 days before treatment (acetaminophen allowed)
Regular use of anticoagulants
Symptoms of locking, intermittent block to range of motion, or loose body sensation that could indicate meniscal displacement or an IA loose body
Corticosteroid injection into the index knee within 3 months prior to screening
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
Patients with known hypersensitivity reactions to ASA or any of its constituents (e.g., HA, dimethyl sulfoxide [DMSO])
Knee surgery on the index knee within 12 months prior to screening and/or planned knee surgery during the study
Knee surgery on the contralateral knee within 6 months prior to screening and/or planned knee surgery during the study
Acute index knee trauma within 3 months prior to screening
Knee effusion requiring aspiration of the index or contralateral knee within 3 months prior to screening
Contralateral knee pain ≥ 4 on the WOMAC Pain scale on most days during the past week.
Current therapy with any immunosuppressive therapy, including corticosteroids (> 5 mg/day of prednisone)
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
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
Active alcohol or substance use disorder, or any other reason that would make it unlikely for the patient to comply with study procedures
Females who are pregnant (positive pregnancy test at screening or prior to treatment) or lactating
Participation in another clinical trial within the 30 days (or 5 half-lives of the investigational compound, whichever is longer) before screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Research Associates	Birmingham	Alabama	United States	35205
2	Alabama Clinical Therapeutics	Birmingham	Alabama	United States	35235
3	AMR Mobile	Mobile	Alabama	United States	36608
4	Arizona Arthritis & Rheumatology Research	Glendale	Arizona	United States	85306
5	Fiel Family & Sports Medicine/ CCT Research	Tempe	Arizona	United States	85283
6	Arizona Arthritis & Rheumatology Research	Tucson	Arizona	United States	85704
7	Tri West Research Associates	El Cajon	California	United States	92020
8	Horizon Clinical Research Center	La Mesa	California	United States	91942
9	Actca, A Member of the Allliance Inc.	Los Angeles	California	United States	90036
10	University of California at Los Angeles	Los Angeles	California	United States	90095
11	Stanford Medicine	Redwood City	California	United States	94063
12	University of California at Davis	Sacramento	California	United States	95186
13	Bone and Joint Institute	Hartford	Connecticut	United States	06106
14	AARDS Research, Inc.	Aventura	Florida	United States	33180
15	Gulfcoast Research Institute	Sarasota	Florida	United States	34232
16	Pinnacle Trials, Inc.	Stockbridge	Georgia	United States	30281
17	Injury Care Research	Boise	Idaho	United States	83713
18	Chicago Clinical Research Institute Inc	Chicago	Illinois	United States	60607
19	Rush University Medical Center	Chicago	Illinois	United States	60612
20	Affinity Health	Oak Brook	Illinois	United States	60523
21	OrthoIndy	Greenwood	Indiana	United States	46143
22	The Spine Network	Shreveport	Louisiana	United States	71101
23	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
24	Klein & Associates, MD, PA	Hagerstown	Maryland	United States	21740
25	Tufts Medical Center	Boston	Massachusetts	United States	02111
26	Methodist Physicians Clinic/ CCT Researc	Fremont	Nebraska	United States	68025
27	Physician Research Collaboration	Lincoln	Nebraska	United States	68516
28	NYU Langone Health	New York	New York	United States	10016
29	Hospital for Special Surgery	New York	New York	United States	10021
30	Lenox Hill Hospital (Northwell Health)	New York	New York	United States	10075
31	M3 Emerging Medical Research, LLC	Durham	North Carolina	United States	27704
32	Moore Orthopedics and Sports Medicine	Morehead City	North Carolina	United States	28557
33	M3 Emerging Medical Research, LLC	Raleigh	North Carolina	United States	27612
34	University Orthopedics Center	Altoona	Pennsylvania	United States	16602
35	University Orthopedic Center	State College	Pennsylvania	United States	16801
36	PCPMG Clinical Research Unit, LLC	Greenville	South Carolina	United States	29501
37	Coastal Carolina Research Center	North Charleston	South Carolina	United States	29406
38	Affinity Health	Nashville	Tennessee	United States	37203
39	Futuro Clinical Trials	McAllen	Texas	United States	78501
40	Spectrum Medical, Inc	Danville	Virginia	United States	24541