Phase Ib Trial of Injectable RAB001 for Knee Osteoarthritis

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of Intra-Articular Injection of RAB001 for Injection in Participants With Knee Osteoarthritis

Обзор

This is a randomized, double-blind, placebo-controlled dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of intra-articular injection of RAB001 in participants with knee osteoarthritis (KOA). The study consists of five dose groups: 1.5 mg, 4.5 mg, 9 mg, 18 mg and 27 mg. A total of 12 participants with knee osteoarthritis will be enrolled per dose group (9 receiving investigational product and 3 receiving placebo), for an overall total enrollment of 60 subjects. The 27 mg cohort serves as an optional escalation group, whose initiation is contingent upon assessment by the Safety Review Committee (SRC). Eligible participants will first receive a single-dose administration followed by a 14-day observation period, during which safety, tolerability, PK and preliminary efficacy data will be collected. In the multiple-dose phase, study treatment will be administered once every 4 weeks for a total of 2 injections, on Week 4 (Day 29) and Week 8 (Day 57), respectively. After the last administration, subjects will enter the follow-up period and return to the study site for safety and efficacy assessments at Weeks 12, 16 and 24. A staggered dose-escalation design will be implemented. Escalation to the next higher dose level may proceed only after completion of the 14-day safety and tolerability evaluation for all subjects in the current dose cohort and subsequent approval from the SRC. Each participant will receive only one assigned dose level throughout the trial.

Вмешательства

• Препарат RAB001 medium dose
  Treatment period: 8 weeks, with study medication administered once every 4 weeks for a total of 3 administrations. All injections shall be performed under full aseptic technique. In case of joint effusion, arthrocentesis shall be conducted prior to study drug administration. The study drug will be injected over approximately 30 to 60 seconds. Subjects shall be monitored for 15 to 30 minutes after injection.

Первичные конечные точки

• Efficacy Endpoints-(WOMAC A1) [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints-WOMAC Scale A (Pain) [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints-WOMAC subscale B (stiffness) [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints-WOMAC subscale C (physical function) [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints-WOMAC subscale C (physical function) [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints [Срок оценки: Weeks 4, 8, 12, 16 and 24]
• Efficacy Endpoints [Срок оценки: Day 1 to Week 24]

Критерии участия

Критерии включения

• (1) Aged from 40 to 75 years inclusive; (2) Diagnosis of knee osteoarthritis consistent with the diagnostic criteria in the Guidelines for the Diagnosis and Treatment of Osteoarthritis issued by the Joint Surgery Group, Orthopaedic Branch of Chinese Medical Association (2024); (3) Received conservative management (e.g., physical therapy, analgesics) for ≥4 weeks with persistent pain in the target knee; the VAS score of WOMAC Item A1 (walking pain) is ≥40 mm and ≤80 mm at screening and baseline; (4) Target knee is graded as Kellgren-Lawrence Grade I-III; the contralateral knee shall not have a higher KL grade than the target knee. In case of identical grades for both knees, the right knee is defined as the target knee; (5) Body mass index (BMI) ranges from 18 to 30 kg/m² inclusive; (6) Provides written informed consent voluntarily prior to any study-related procedures.

Критерии исключения

• (1) Unable to ambulate (subjects using walking aids for ≥12 weeks prior to screening visit may continue such aids throughout the study); (2) VAS pain score ≥40 mm in any joint other than the target knee at screening and baseline visits.

(3) Subjects with osteoarthritis of the ipsilateral hip; (4) Subjects with substantial target-knee joint effusion judged by the investigator to be ineligible for enrollment; (5) Subjects with active septic arthritis of the target knee, skin breakdown/infection at the injection site, or any significant chronic dermatosis that may interfere with intra-articular injection and/or injection-site safety assessment; (6) Subjects unable to discontinue permitted analgesics within 48 hours prior to efficacy assessments; (7) Subjects receiving systemic corticosteroids within 12 weeks before screening; (8) Subjects with septic arthritis in any joint within 12 weeks before screening; (9) Subjects exposed to any investigational medicinal product, device or biologic within 12 weeks before screening; (10) Subjects receiving intra-articular corticosteroid injection into the target knee within 24 weeks before screening; (11) Subjects receiving viscosupplementation injection (sodium hyaluronate, medical chitosan) in the target knee within 24 weeks before screening; (12) Subjects who underwent major lower-extremity surgery, arthroplasty or arthroscopy on target knee or other lower-limb joints within 24 weeks before screening, or with planned lower-limb surgery during study period; (13) Subjects with secondary knee osteoarthritis induced by acute disease or trauma within 5 years before screening; (14) Subjects with active malignancy or history of anti-tumor therapy within 5 years before screening, excluding non-melanoma skin cancer; (15) Subjects with inflammatory arthropathies or relevant disorders involving joints (e.g., rheumatoid arthritis, metabolic bone disease, psoriatic arthritis, gout, symptomatic chondrocalcinosis, osteonecrosis or active infection); (16) Subjects with marked varus/valgus deformity, ligamentous laxity or unstable meniscus; (17) Subjects with chronic painful conditions (VAS ≥40 mm) at screening or peripheral/central neuropathy impairing sensory function around target knee, including but not limited to back pain, hip pain, intervertebral disc herniation, sciatica, diabetic neuropathy, post-stroke pain or fibromyalgia; (18) Subjects with pulmonary diseases such as asthma or COPD requiring regular systemic/inhaled corticosteroid treatment during study; (19) Subjects with venous or lymphatic stasis of lower extremities; (20) Subjects with claudication or peripheral arterial disease; (21) Subjects on ongoing oral/parenteral anticoagulation or high-dose antiplatelet therapy (daily aspirin ≤100 mg and/or antiplatelet agents such as clopidogrel, ticagrelor are permitted); (22) Subjects on chronic regular intake of paracetamol or nonsteroidal anti-inflammatory drugs (NSAIDs); (23) Subjects with severe systemic illnesses including myocardial infarction, heart failure, unstable angina, cerebrovascular disease, severe renal insufficiency, etc.; (24) Subjects with severe hepatic impairment or relevant medical history; (25) Subjects with abnormal coagulation parameters; (26) Subjects with known hypersensitivity to any component of investigational product or paracetamol, or severe allergic constitution as assessed by investigator; (27) Female subjects with positive pregnancy test, breastfeeding, unwilling to implement effective contraception or planning pregnancy during trial; (28) Subjects with any other conditions deemed inappropriate for study enrollment by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Peking Union Medical College Hospital, Chinese Academy of Medical Sciences — Beijin
• The Third Hospital of Hebei Medical University — Shijiazhuang

Идентификаторы

NCT: NCT07652372 · LBRC_RAB001_OA_PHI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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