Safety and Efficacy of RHH646 for Knee Osteoarthritis

NCT05816395 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CRHH646A122012022-502821-16-00
• Study Type: interventional
• Target: 82
• Locations: 5 countries
• Sites: 10

Brief Summary

The purpose of this study was 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.

Conditions

Osteoarthritis, Knee

Keywords

Tibiofemoral OA; K&L grade 2 to 3 OA in the target knee; Oral RHH646 treatment

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Cartilage Volume in the Index Region of the Target Knee by MRI

  Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in the volume of cartilage in the index region. The index region was defined as the combination of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

  Baseline, Week 52

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Number of participants with treatment emergent adverse events (any AE regardless of seriousness), and SAEs.

  Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 56 weeks.

Secondary Outcomes (1)

• Pharmacokinetic (PK) Parameter: RHH646 Plasma Concentrations

  Baseline (4 hours post dose), Week 4 (pre dose)

Study Arms (2)

RHH646 75 mg

EXPERIMENTAL

RHH646 was administered orally once per day for a year.

Drug: RHH646

Placebo

PLACEBO COMPARATOR

Matching Placebo was administered orally once per day for a year.

Drug: Placebo

Interventions

RHH646 DRUG

RHH646 capsule for oral use

RHH646 75 mg

Placebo DRUG

RHH646 placebo capsule for oral use

Placebo

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Clinical Trials Research

Lincoln, California, 95648, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Clinical Trial Network

Houston, Texas, 77074, United States

Location

Pioneer Research Solutions

Sugar Land, Texas, 77479, United States

Location

Novartis Investigative Site

Buenos Aires, C1055AAF, Argentina

Location

Novartis Investigative Site

Caba, C1015ABO, Argentina

Location

Novartis Investigative Site

Gandrup, 9362, Denmark

Location

Novartis Investigative Site

Herlev, 2730, Denmark

Location

Novartis Investigative Site

Warsaw, 00-874, Poland

Location

Novartis Investigative Site

Santiago, A Coruna, 15705, Spain

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2023
• First Posted: April 18, 2023
• Study Start: May 31, 2023
• Primary Completion: February 24, 2025
• Study Completion: February 24, 2025
• Last Updated: March 31, 2026
• Results First Posted: February 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (2); PL (1); US (4); AR (2); ES (1)