Safety and Efficacy of RHH646 for Knee Osteoarthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the articular cartilage-regenerating capacity of RHH646 in the knee as well as to assess safety and tolerability in participants with knee osteoarthritis. The treatment duration will be up to 52 weeks. The total study duration for an individual participant will be up to 62 weeks.

Official Title
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A Randomized, Placebo Controlled, Investigator and Participant-blinded Study Investigating Safety, Tolerability, and Efficacy of RHH646 in Participants With Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: RHH646
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is ≥35 and ≤75 years old, at time of screening Participants must weigh at least 50 kg to participate in the study and must have a body mass index (BMI) ≤35 kg/m2. BMI = Body weight (kg) / [Height (m)]2 Diagnosis of tibiofemoral OA in at least one knee by standard American College of Rheumatology (ACR) clinical and radiographic criteria (Altman et al 1986) at screening K&L grade 2 to 3 OA in the target knee evaluated with X-Ray by the Central Reader at screening Joint Space Width (JSW) of 2.00 to 4.00 mm for males and 1.5 to 3.5 mm for females (X=0.225 fixed position according to Neumann et al 2009) in the target knee evaluated with X-Ray by the Central Reader at screening Symptomatic disease, defined as having pain in the knee at least 3 days per week during the last 3 months from screening that is relieved by analgesic therapy (e.g. acetaminophen or non-steroidal anti-inflammatory drugs), according to the investigator's evaluation and judgment of the patient's history Exclusion Criteria: Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception Arthroscopy of the target knee within the 6 months prior to screening or planned arthroscopy during the study Previous surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy >50% or osteotomy; planned surgery for either knee during the study Unstable target knee joint (including, but not limited to, post-traumatic or congenital laxity) or insufficiently reconstructed ligaments based on medical history and/or physical examination by the investigator Participant has severe malalignment (valgus or varus deformity) in the target knee >7.5° based on X-ray evaluation by the Central Reader at screening. K&L grade 4 OA in either knee Presence of severe hip OA that either (i) alters lower limb function to a degree that increases or abnormally changes the mechanical forces in the knee while walking, according to investigator's evaluation or (ii) currently requires or is likely to require specific medical or surgical management during the study period Other pathologies affecting the knee, including subchondral insufficiency fractures, bone fracture (acute or subacute within the 6 months prior to screening) or bone bruise, osteonecrosis, malignant bone marrow infiltration, solid tumors, and/or patellofemoral dysplasia based on clinical assessment, or imaging Known autoimmune disease with inflammatory arthritis (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus), crystal-induced arthritides (gout or pseudogout arthritis), active acute or chronic infection of the knee joint, Lyme disease involving the knee, reactive arthritis, systemic cartilage disorders, moderate to severe fibromyalgia, a known systemic connective tissue disease or a widespread pain index >4. Inability to undergo MRI (e.g., claustrophobia, body size, leg not fitting in the coil) or contraindications to MRI (e.g., non MRI-compatible metallic implants, metallic foreign bodies, pacemaker, defibrillator)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RHH646<br>RHH646 | Drug: RHH646<br>* RHH646 capsule for oral use<br>|
| Placebo Comparator: Placebo<br>RHH646 placebo | Drug: Placebo<br>* RHH646 placebo capsule for oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in cartilage volume in the index region of the target knee by magnetic resonance imaging at Week 52 | Change in cartilage volume in certain regions in the knee measured by magnetic resonance imaging at Week 52 compared to the volume prior to receiving RHH646 | Baseline and Week 52 | 
| Number of participants with Adverse Events | Adverse events and clinically notable findings in vital signs, ECG, hematology, blood chemistry, and urinalysis | From start of treatment until study completion (approximately 14 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RHH646 plasma concentrations | Concentration of RHH646 in plasma | Baseline, up to End of Study visit (approximately month 13) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tibiofemoral OA, K&L grade 2 to 3 OA in the target knee, Oral RHH646 treatment