Safety and Efficacy of RHH646 for Knee Osteoarthritis

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: RHH646; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1015ABO
      • Novartis Investigative Site
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1055AAF
      • Novartis Investigative Site
• Denmark
  • Gandrup, Denmark, 9362
    • Novartis Investigative Site
  • Herlev, Denmark, 2730
    • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 00-874
    • Novartis Investigative Site
• Spain
  • A Coruna
    • Santiago De Compostela, A Coruna, Spain, 15705
      • Novartis Investigative Site
• United States
  • California
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
  • Florida
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Texas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network .
    • Sugar Land, Texas, United States, 77479
      • Pioneer Research Solutions .

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RHH646	Drug: RHH646; RHH646 capsule for oral use
Placebo Comparator: Placebo; RHH646 placebo	Drug: Placebo; RHH646 placebo capsule for oral use

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2023
• Primary Completion (Estimated): February 13, 2025
• Study Completion (Estimated): February 13, 2025

Study Registration Dates

• First Submitted: January 31, 2023
• First Submitted That Met QC Criteria: March 31, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Tibiofemoral OA; K&L grade 2 to 3 OA in the target knee; Oral RHH646 treatment
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: CRHH646A12201; 2022-502821-16-00 (Other Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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