A Study on Visco-antalgic Intra-articular Administration in Symptomatic Knee Osteoarthritis

A Two-stage 6-month Multicentre, Randomised, Double-blind, Controlled Study on the Safety and Efficacy Intra-articular Administration of JTA-004 in Patients With Symptomatic Knee Osteoarthritis

Osteoarthritis (OA) is the most common joint disease affecting millions of people around the world, for which there is unfortunately no cure. Among existing therapies, viscosupplementation, i.e., the injection of hyaluronic acid into the joint, has an established place in the symptomatic treatment of knee OA.

The present Phase IIb/III aiming to assess the safety and efficacy of JTA-004 is organized in two phases. With results obtained in the first phase the best dose of JTA-004 is determined, and the efficacy of the selected dose will then be confirmed in the second phase.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Device: Reference product intra-articular injection; Drug: JTA-004 intra-articular injection

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ambulatory

• Diagnosed with primary knee osteoarthritis, fulfilling the following American College of Rheumatology (ACR) criteria at the target knee:

  • Pain ≥ 40 mm on a 0-100 mm VAS during the 3 days preceding the date of the screening visit
  • Morning stiffness not exceeding 30 minutes
  • Kellgren-Lawrence grade II or III
• Insufficient / failed response to analgesic and / or NSAIDs
• No physical therapy of the knee, and knee braces for the entire duration of study
• Ability to provide a written, dated, and signed informed consent prior to any study related procedure, and to understand and comply with study requirements

Exclusion Criteria:

Current symptoms and/or signs related to the disease under study:

• Isolated symptomatic femoropatellar OA of the target knee
• History of trauma or surgery or arthroscopy at the target knee within 6 months before inclusion
• Concomitant inflammatory disease or other condition affecting the joints (e.g., rheumatoid arthritis, septic arthritis, inflammatory joint disease, metabolic bone disease, psoriasis, gout, microcrystalline arthropathies/chondrocalcinosis, Paget's disease)
• Any musculoskeletal condition (such as hip osteoarthritis, amputation, neurologic disorder) that would impede measurement of efficacy at target knee
• Target knee prosthesis planned within 12 months after the Screening Visit

Current or previous diagnoses, signs and/or symptoms:

• Uncontrolled diabetes mellitus, end-stage hepatic or renal disease
• Current (or within the last 5 years prior to entering the study) history of solid or haematological neoplasia or bone marrow transplantation (except for basal cell carcinoma and completely excised squamous cell carcinoma)
• Other severe acute or chronic medical or psychiatric conditions or pre-dispositions or laboratory abnormalities, as judged by the Investigator
• Current or past history of coagulation disorders, as judged by the Investigator
• Hypersensitivity to any components of HA-based injection products
• History of hypersensitivity to human biological material including blood and blood derived products, potential excipients and residues from manufacturing process documented clinically or by laboratory tests
• Hypersensitivity to avian proteins
• Life expectancy less than 6 months

Current or previous treatment:

• Participation in another clinical study within 6 months prior to Screening
• Patients previously treated with JTA-004

• Treatment:

  • Within 6 months prior to Screening: intra-articular hyaluronic acid injection at the target knee
  • Within 2 months prior to Screening: intra-articular glucocorticoids at the target knee
• Current chemo-, radio- or immuno-cancer-therapy or immunosuppressive therapy
• Current anti-hypertensive medication the effects of which are known to be potentiated by a single dose of clonidine
• Current (or within 6 months prior to Screening) illicit drug abuse

Safety aspects concerning female subjects of childbearing potential:

• Females who are pregnant, lactating or woman with childbearing potential (last menstrual bleeding less than 12 months ago) unwilling to use medically acceptable contraception, or women with childbearing potential unwilling to perform a pregnancy test before administration of study treatment.

Other exclusion criteria:

• Body Mass Index (BMI) of 35 kg/m2 or greater

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Reference product; Hylan G-F 20	Device: Reference product intra-articular injection; Each patient will undergo a single injection of Reference product into the knee joint
Experimental: JTA-004 50 (2 ml); Sodium hyaluronate, plasma proteins and clonidine	Drug: JTA-004 intra-articular injection; Each patient will undergo a single injection of JTA-004 into the knee joint
Experimental: JTA-004 50 (4 ml); Sodium hyaluronate, plasma proteins and clonidine	Drug: JTA-004 intra-articular injection; Each patient will undergo a single injection of JTA-004 into the knee joint
Experimental: JTA-004 100 (2 ml); Sodium hyaluronate, plasma proteins and clonidine	Drug: JTA-004 intra-articular injection; Each patient will undergo a single injection of JTA-004 into the knee joint

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in WOMAC VA3.1 Pain Subscale Score at Month 6	The primary endpoint is the Western Ontario McMaster universities (WOMAC®) VA3.1 Pain Subscale (subscale A): the individual changes in WOMAC® VA3.1 Pain Subscale Score between Baseline and Month 6 were calculated and compared by analysis of covariance (ANCOVA), adjusted for baseline value, to the Reference group. Results are expressed as "adjusted mean" based on the model used for group comparison. WOMAC Osteoarthritis Index is a tri-dimensional, self-administered, patient-centred health status questionnaire for knee disease severity ans osteonecrosis symptoms. The WOMAC® Index Pain Subscale (VAS format) was used. The VAS score was determined by measuring in millimetres from the left-hand end of the line to the point that the patient marks (0-100 mm) for 5 questions. Results are summed and normalized on a 100 mm scale: 0 represents no knee pain and 100 extreme knee pain.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC® Pain Subscale at Month 3	The primary endpoint is the Western Ontario McMaster universities (WOMAC®) VA3.1 Pain Subscale (subscale A): the individual changes in WOMAC® VA3.1 Pain Subscale Score between Baseline and Month 3 were calculated and compared by analysis of covariance (ANCOVA), adjusted for baseline value, to the Reference group. Results are expressed as "adjusted mean" based on the model used for group comparison. WOMAC Osteoarthritis Index is a tri-dimensional, self-administered, patient-centred health status questionnaire for knee disease severity ans osteonecrosis symptoms. The WOMAC® Index Pain Subscale (VAS format) was used. The VAS score was determined by measuring in millimetres from the left-hand end of the line to the point that the patient marks (0-100 mm) for 5 questions. Results are summed and normalized on a 100 mm scale: 0 represents no knee pain and 100 extreme knee pain.	Baseline and 3 months
WOMAC® Total Score Over Time	The Western Ontario McMaster universities (WOMAC®) VA3.1 Total Score was used: the individual changes in WOMAC VA3.1 Total Score between Baseline and 2 weeks were calculated and compared by Mixed-Effect Model for Repeated Measurements, adjusted for baseline value, to the Reference group. Results are expressed as "adjusted mean" based on the model used for group comparison. WOMAC Osteoarthritis Index is a tri-dimensional, self-administered, patient-centred health status questionnaire for knee disease severity and osteonecrosis symptoms. The Total score (VAS format) was determined by measuring in millimetres from the left hand end of the line to the point that the patient marks (0-100 mm) for the pain (5 questions), stiffness (2 questions), and physical function (17 questions). Results are normalized on a 0-100 mm scale format. A higher score represents a higher degree of k	Baseline and 2 weeks
WOMAC® Total Score Over Time	The Western Ontario McMaster universities (WOMAC®) VA3.1 Total Score was used: the individual changes in WOMAC VA3.1 Total Score between Baseline and Month 3 were calculated and compared by Mixed-Effect Model for Repeated Measurements, adjusted for baseline value, to the Reference group. Results are expressed as "adjusted mean" based on the model used for group comparison. WOMAC Osteoarthritis Index is a tri-dimensional, self-administered, patient-centred health status questionnaire for knee disease severity ans osteonecrosis symptoms. The Total score (VAS format) was determined by measuring in millimetres from the left hand end of the line to the point that the patient marks (0-100 mm) for the pain (5 questions), stiffness (2 questions), and physical function (17 questions). Results are normalized on a 0-100 mm scale format. A higher score represents a higher degree of knee disease severity.	Baseline and 3 months
WOMAC® Total Score Over Time	The Western Ontario McMaster universities (WOMAC®) VA3.1 Total Score was used: the individual changes in WOMAC VA3.1 Total Score between Baseline and Month 6 were calculated and compared by Mixed-Effect Model for Repeated Measurements, adjusted for baseline value, to the Reference group. Results are expressed as "adjusted mean" based on the model used for group comparison. WOMAC Osteoarthritis Index is a tri-dimensional, self-administered, patient-centred health status questionnaire for knee disease severity ans osteonecrosis symptoms.The Total score (VAS format) was determined by measuring in millimetres from the left hand end of the line to the point that the patient marks (0-100 mm) for the pain (5 questions), stiffness (2 questions), and physical function (17 questions). Results are normalized on a 0-100 mm scale format. A higher score represents a higher degree of knee disease severity.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: Bone Therapeutics S.A

Publications and helpful links

General Publications

• Bettonville M, Leon M, Margaux J, Urbin-Choffray D, Theunissen E, Besse-Hammer T, Fortems Y, Verlinden S, Godeaux O, Delmarcelle AS, Kaux JF. Safety and efficacy of a single intra-articular injection of a novel enhanced protein solution (JTA-004) compared to hylan G-F 20 in symptomatic knee osteoarthritis: a randomized, double-blind, controlled phase II/III study. BMC Musculoskelet Disord. 2021 Oct 19;22(1):888. doi: 10.1186/s12891-021-04750-3.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): April 27, 2018
• Study Completion (Actual): April 27, 2018

Study Registration Dates

• First Submitted: April 13, 2016
• First Submitted That Met QC Criteria: April 14, 2016
• First Posted (Estimate): April 15, 2016

Study Record Updates

• Last Update Posted (Actual): December 6, 2021
• Last Update Submitted That Met QC Criteria: October 29, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: osteoarthritis; knee; arthritis; intra-articular injection; viscosupplement; degenerative
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: JTA-KOA1

Drug and device information, study documents

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