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

Phase 2

Completed

Conditions: Knee Osteoarthritis

Interventions: Drug: JTA-004 intra-articular injection
Device: Reference product intra-articular injection

Registration Number: NCT02740231

Lead Sponsor: Bone Therapeutics S.A

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 173

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
JTA-004 50 (4 ml)	JTA-004 intra-articular injection	Sodium hyaluronate, plasma proteins and clonidine
JTA-004 50 (2 ml)	JTA-004 intra-articular injection	Sodium hyaluronate, plasma proteins and clonidine
JTA-004 100 (2 ml)	JTA-004 intra-articular injection	Sodium hyaluronate, plasma proteins and clonidine
Reference product	Reference product intra-articular injection	Hylan G-F 20

Primary Outcome Measures

Name	Time	Method
Change From Baseline in WOMAC VA3.1 Pain Subscale Score at Month 6	Baseline and 6 months	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.

Secondary Outcome Measures

Name	Time	Method
WOMAC® Pain Subscale at Month 3	Baseline and 3 months	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.
WOMAC® Total Score Over Time	Baseline and 6 months	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.