Phase Ib Trial of Injectable RAB001 for Knee Osteoarthritis (LBRC_RAB001_OA)

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: RAB001 medium dose

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijin
    • Beijin, Beijin, China, 100730
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • The Third Hospital of Hebei Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• (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.

Exclusion Criteria:

• (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.5 mg; 9 subjects and 3 receive placebo.	Drug: 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.
Experimental: 4.5 mg; 9 subjects and 3 receive placebo.	Drug: 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.
Experimental: 9 mg; 9 subjects and 3 receive placebo.	Drug: 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.
Experimental: 18 mg; 9 subjects and 3 receive placebo.	Drug: 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.
Experimental: 27 mg; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Endpoints(if any)	Changes from baseline in target knee cartilage volume assessed by MRI at Weeks 12 and 24;	Weeks 12 and 24
Efficacy Endpoints(if any)	Changes from baseline in target knee MOAKS score assessed by MRI at Weeks 12 and 24;	Weeks 12 and 24
Efficacy Endpoints(if any)	Changes from baseline in bone mineral density (BMD) of proximal tibial epiphysis of the target knee measured via dual-energy X-ray absorptiometry (DXA) scan at Week 24;	Week 24
Efficacy Endpoints(if any)	Changes from baseline in serum CTX-I and CTX-II concentrations measured at Weeks 12 and 24.	Weeks 12 and 24

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: June 11, 2026
• First Submitted That Met QC Criteria: June 16, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: knee osteoarthritis; RAB001; LLP2A-Alendronate
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: LBRC_RAB001_OA_PHI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Based on a comprehensive consideration of ethical compliance (informed consent), legal constraints, protection of commercial interests, and operational feasibility, individual participant data (IPD) will not be shared.

Drug and device information, study documents

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