Phase Ib Trial of Injectable RAB001 for Knee Osteoarthritis

NCT07652372 | Enrolling By Invitation Phase 1

• 1 other identifier: LBRC_RAB001_OA_PHI
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Knee Osteoarthritis

Keywords

knee osteoarthritis; RAB001; LLP2A-Alendronate

Outcome Measures

Primary Outcomes (30)

• Efficacy Endpoints-(WOMAC A1)

  Changes from baseline in the walking pain score of target knee (WOMAC A1). WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints-WOMAC Scale A (Pain)

  Change from baseline in target knee WOMAC Scale A (Pain) score at Weeks 4, 8, 12, 16 and 24

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints-WOMAC subscale B (stiffness)

  Change from baseline in target knee WOMAC subscale B (stiffness) score at Weeks 4, 8, 12, 16 and 24. WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints-WOMAC subscale C (physical function)

  Change from baseline in target knee WOMAC subscale C (physical function) score at Weeks 4, 8, 12, 16 and 24. WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints-WOMAC subscale C (physical function)

  Change from baseline in target knee total WOMAC score at Weeks 4, 8, 12, 16 and 24. WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints

  Percentage of responders per( OMERACT-OARSI )response criteria at Weeks 4, 8, 12, 16 and 24

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints

  Changes from baseline in the five KOOS subdomain scores (pain, symptoms, activities of daily living, sport and recreation function, knee-related quality of life) for the target knee at Weeks 4, 8, 12, 16 and 24. KOOS =Knee injury and Osteoarthritis Outcome Score

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints

  Changes from baseline in Patient Global Assessment (PGA) score at Weeks 4, 8, 12, 16 and 24

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints

  Changes from baseline in Clinician's Global Assessment (COGA) score at Weeks 4, 8, 12, 16 and 24

  Weeks 4, 8, 12, 16 and 24

• Efficacy Endpoints

  Cumulative intake of rescue medication (paracetamol / acetaminophen) throughout the study period.

  Day 1 to Week 24

• Pharmacokinetic (PK) Endpoints Cmax

  Maximum observed plasma concentration

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-AUC₀-ₜ

  Area under the concentration-time curve from time 0 to last measurable time point

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-AUC₀-∞

  Area under the concentration-time curve from time 0 to infinity

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-AUC_%Extrap

  Percentage of AUC extrapolation

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-Tmax

  Time to reach maximum concentration

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-t₁/₂z

  Terminal elimination half-life

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-Vz/F

  Apparent volume of distribution (terminal phase, extravascular route)

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-CLz/F

  Apparent total clearance (terminal phase, extravascular route)

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-λz

  Terminal elimination rate constant

  Single-dose Administration Phase: Within 1 hour prior to injection on Day 1 (0 hour), and at 5 , 10 , 15 , 30 minutes, 1 , 2 , 4 , 8 , 12 and 24 hours after injection initiation. A total of 11 blood collection time points are included.

• Pharmacokinetic (PK) Endpoints-Css,max

  Steady-state maximum concentration

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-Css,min

  Steady-state minimum concentration

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-Css,av

  Average steady-state concentration

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-AUC₀-τ

  Area under the curve over one dosing interval

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-CLss/F

  Apparent total clearance at steady state

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-Vz,ss/F

  Apparent volume of distribution at steady state

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-Ra(Cmax)

  Accumulation ratio of maximum concentration

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-Ra(AUC)

  Accumulation ratio of AUC

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Pharmacokinetic (PK) Endpoints-DF

  Fluctuation degree / Degree of fluctuation

  Multiple-dose Administration Phase: Within 1 hour prior to injection initiation on Day 29 (0 hour), within 1 hour prior to injection initiation on Day 57 (0 hour), and at 5, 10, 15, 30 minutes, 1, 2, 4, 8, 12 and 24 hours after injection initiation.

• Safety Endpoints-AE(adverse events)

  Safety assessments and grading of adverse events (AEs) occurring throughout the study period were performed in accordance with NCI-CTCAE Version 5.0.

  Day 1 to Week 24

• Safety Endpoints-SAE(Serious adverse events)

  Safety assessed by CTCAE v5.0 of the SAE(Serious adverse events) during the study.

  Day 1 to Week 24

Other Outcomes (4)

• Efficacy Endpoints(if any)

  Weeks 12 and 24

• Efficacy Endpoints(if any)

  Weeks 12 and 24

• Efficacy Endpoints(if any)

  Week 24

Study Arms (5)

1.5 mg

EXPERIMENTAL

9 subjects and 3 receive placebo.

Drug: RAB001 medium dose

4.5 mg

EXPERIMENTAL

9 subjects and 3 receive placebo.

Drug: RAB001 medium dose

9 mg

EXPERIMENTAL

9 subjects and 3 receive placebo.

Drug: RAB001 medium dose

18 mg

EXPERIMENTAL

9 subjects and 3 receive placebo.

Drug: RAB001 medium dose

27 mg

EXPERIMENTAL

9 subjects and 3 receive placebo.The 27 mg cohort is an optional dose-escalation group, and its implementation will be determined based on the assessment from the Safety Review Committee (SRC).

Drug: RAB001 medium dose

Interventions

RAB001 medium dose DRUG

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.

1.5 mg; 18 mg; 27 mg; 4.5 mg; 9 mg

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• (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.

Sponsors & Collaborators

• ZhongShan LaiBo RuiChen BioMedicine Co.,Ltd.: lead

Study Sites (2)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijin, Beijin, 100730, China

Location

The Third Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050051, China

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 17, 2026
• Study Start: April 16, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: June 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)