NCT05816395

Safety and Efficacy of RHH646 for Knee Osteoarthritis

Completed Phase 2 Results posted Last updated 31 March 2026

What this trial tests

Phase 2 trial testing RHH646 in Osteoarthritis, Knee in 82 participants. Completed in 24 February 2025.

Timeline

31 May 2023

Primary endpoint
24 February 2025

24 February 2025

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	82
Start date	31 May 2023
Primary completion	24 February 2025
Estimated completion	24 February 2025
Sites	10 locations across Denmark, Poland, Argentina, United States, Spain

Drugs / interventions tested

• RHH646 — full drug profile →
• Placebo

Conditions studied

• Osteoarthritis, Knee — all drugs for Osteoarthritis, Knee →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 35 to 75, any sex, with Osteoarthritis, Knee. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Cartilage Volume in the Index Region of the Target Knee by MRI Primary · Baseline, Week 52

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.

Group	Value	95% CI
RHH646 75 mg	94.6	± 36.67
Placebo	9.3	± 38.15

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · 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.

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

Adverse Events

Group	Value	95% CI
RHH646 75 mg	34
Placebo	35

Serious Adverse Events

Group	Value	95% CI
RHH646 75 mg	1
Placebo	3

Pharmacokinetic (PK) Parameter: RHH646 Plasma Concentrations Secondary · Baseline (4 hours post dose), Week 4 (pre dose)

RHH646 concentration was determined by a validated LC-MS/MS method; the anticipated Lower Limit of Quantification (LLOQ) was 2 ng/mL. RHH646 concentrations below the lower limit of quantification (LLOQ) were treated as "zero" .

Baseline (4 hours post dose)

Group	Value	95% CI
RHH646 75 mg	541	± 186

Week 4 (pre dose)

Group	Value	95% CI
RHH646 75 mg	726	± 239

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

RHH646 75 mg

Serious: 1/41 (2%)

Deaths: 0/41

Placebo

Serious: 3/41 (7%)

Deaths: 0/41

Total

Serious: 4/82 (5%)

Deaths: 0/82

Serious adverse events (5 terms)

Reaction	System	RHH646 75 mg	Placebo	Total
Erysipelas	Infections and infestations	—	—	—
Large intestine infection	Infections and infestations	—	—	—
Postoperative wound infection	Infections and infestations	—	—	—
Limb injury	Injury, poisoning and procedural complications	—	—	—
Meniscus injury	Injury, poisoning and procedural complications	—	—	—

Other adverse events (96 terms — click to expand)

Reaction	System	RHH646 75 mg	Placebo	Total
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Influenza	Infections and infestations	—	—	—
Influenza like illness	General disorders and administration site conditions	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Hypertension	Vascular disorders	—	—	—
Gastroenteritis viral	Infections and infestations	—	—	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Goitre	Endocrine disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Oedema peripheral	General disorders and administration site conditions	—	—	—
Pyrexia	General disorders and administration site conditions	—	—	—
Localised infection	Infections and infestations	—	—	—
Otitis externa	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Tooth infection	Infections and infestations	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—
Blood pressure increased	Investigations	—	—	—
Joint swelling	Musculoskeletal and connective tissue disorders	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—
Plantar fasciitis	Musculoskeletal and connective tissue disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Atrioventricular block first degree	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Tinnitus	Ear and labyrinth disorders	—	—	—
Tympanic membrane perforation	Ear and labyrinth disorders	—	—	—
Adrenal insufficiency	Endocrine disorders	—	—	—
Corneal disorder	Eye disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Abdominal tenderness	Gastrointestinal disorders	—	—	—
Colitis microscopic	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: Erysipelas, Large intestine infection, Postoperative wound infection, Limb injury, Meniscus injury.

Data from ClinicalTrials.gov NCT05816395 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.