Safety and Efficacy of RHH646 for Knee Osteoarthritis

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05816395
• Other study ID #: CRHH646A12201
• Secondary ID: 2022-502821-16-0
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 31, 2023
• Est. completion date: February 13, 2025

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 82
• Est. completion date: February 13, 2025
• Est. primary completion date: February 13, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

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 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
• Predominantly medial tibiofemoral compartment involvement defined as medial Joint Space Narrowing (medJSN) 1-2 (Altman et al 1995; Altman, Gold 2007) and medJSN > lateral Joint Space Narrowing (latJSN) in the target knee evaluated with X-Ray by the Central Reader at screening
• Symptomatic disease, defined as having pain in the target 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. In EEA countries, women of child-bearing potential will be excluded from participation in this trial, irrespective of the use of 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)

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• RHH646
RHH646 capsule for oral use
• Placebo
RHH646 placebo capsule for oral use

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Denmark	Novartis Investigative Site	Gandrup
Denmark	Novartis Investigative Site	Herlev
Poland	Novartis Investigative Site	Warszawa
Spain	Novartis Investigative Site	Santiago De Compostela	A Coruna
United States	Clinical Trial Network .	Houston	Texas
United States	Clinical Trials Research	Lincoln	California
United States	Pioneer Research Solutions .	Sugar Land	Texas
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Denmark,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	RHH646 plasma concentrations	Concentration of RHH646 in plasma	Baseline, up to End of Study visit (approximately month 13)