Osteoarthritis, KneePhase 2NCT05816395
Safety and Efficacy of RHH646 for Knee Osteoarthritis
A Phase 2 study testing RHH646 in people with Osteoarthritis, Knee, run by Novartis Pharmaceuticals at 10 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- RHH646
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 10 sitesin 5 countries
- Study dates
- 31 May 2023to 24 Feb 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
United States4 sites
Clinical Trial Network
Houston, Texas, 77074
Clinical Trials Research
Lincoln, California, 95648
Pioneer Research Solutions
Sugar Land, Texas, 77479
Conquest Research
Winter Park, Florida, 32789
Argentina2 sites
Novartis Investigative Site
Buenos Aires, C1055AAF
Novartis Investigative Site
Caba, C1015ABO
Denmark2 sites
Novartis Investigative Site
Gandrup, 9362
Novartis Investigative Site
Herlev, 2730
About this study
Official title: 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 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.
Read the detailed description
This was a non-confirmatory, randomized, Investigator and participant blinded, two-arm, placebo controlled, Phase IIa study to assess safety, tolerability, and efficacy of orally administered RHH646 in adult participants with symptomatic, mild to moderate radiographic knee osteoarthritis in the target knee and with pain requiring analgesic therapy.
The study comprised of a Screening period (up to 6 weeks), a treatment period (52 weeks) and a follow up period (4 weeks after the last administration of study treatment) before the End of Study (EOS) visit. The total duration for each participant was up to 62 weeks.
- Conditions
- Osteoarthritis, Knee
- Being tested
- RHH646, Placebo
- Keywords
- Tibiofemoral OA, K&L grade 2 to 3 OA in the target knee, Oral RHH646 treatment
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RHH646Drug
RHH646 capsule for oral use
PlaceboDrug
RHH646 placebo capsule for oral use
| Study group | Role | What they receive |
|---|---|---|
| RHH646 75 mg | Experimental | RHH646 was administered orally once per day for a year. Receives: Drug: RHH646 |
| Placebo | Placebo comparator | Matching Placebo was administered orally once per day for a year. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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" .
Measured: Baseline (4 hours post dose), Week 4 (pre dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2023
- Study start31 May 2023
- Primary completion24 Feb 2025
- Study completion24 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05816395
- Sponsor's protocol ID
- CRHH646A12201
- Other IDs
- 2022-502821-16-00
- Status last verified
- Mar 2026
- First submitted
- 31 Jan 2023
- Last updated
- 31 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo Controlled, Investigator and Participant-blinded Study Investigating Safety, Tolerability, and Efficacy of RHH646 in Participants With Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT05816395
- Acronym / sponsor ID
- CRHH646A12201
- Conditions
- Osteoarthritis, Knee
- Keywords
- Tibiofemoral OA, K&L grade 2 to 3 OA in the target knee, Oral RHH646 treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 31 May 2023 (actual)
- Primary completion
- 24 Feb 2025 (actual)
- Study completion
- 24 Feb 2025 (actual)
- First posted
- 18 Apr 2023 (actual)
- Results
- Posted 17 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This was a non-confirmatory, randomized, Investigator and participant blinded, two-arm, placebo controlled, Phase IIa study to assess safety, tolerability, and efficacy of orally administered RHH646 in adult participants with symptomatic, mild to moderate radiographic knee osteoarthritis in the target knee and with pain requiring analgesic therapy.
The study comprised of a Screening period (up to 6 weeks), a treatment period (52 weeks) and a follow up period (4 weeks after the last administration of study treatment) before the End of Study (EOS) visit. The total duration for each participant was up to 62 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RHH646 75 mg | Experimental | Drug: RHH646RHH646 was administered orally once per day for a year. |
| Placebo | Placebo comparator | Drug: PlaceboMatching Placebo was administered orally once per day for a year. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RHH646RHH646 capsule for oral use | Drug | RHH646 75 mg |
| PlaceboRHH646 placebo capsule for oral use | Drug | Placebo |
Primary outcome
Change From Baseline in Cartilage Volume in the Index Region of the Target Knee by MRI
Time frame: 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.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Number of participants with treatment emergent adverse events (any AE regardless of seriousness), and SAEs.
1 secondary outcome
Pharmacokinetic (PK) Parameter: RHH646 Plasma Concentrations
Time frame: Baseline (4 hours post dose), Week 4 (pre dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RHH646 in people with Osteoarthritis, Knee, run by Novartis Pharmaceuticals at 10 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Argentina, Denmark, Poland, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Cartilage Volume in the Index Region of the Target Knee by MRI (time frame: Baseline, Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.