Clinical trial NCT05816395: Safety and Efficacy of RHH646 for Knee Osteoarthritis
Official title: A Randomized, Placebo Controlled, Investigator and Participant-blinded Study Investigating Safety, Tolerability, and Efficacy of RHH646 in Participants With Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: Tibiofemoral OA
K&L grade 2 to 3 OA in the target knee
Oral RHH646 treatment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-04-18
Enrollment: 82
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Change from baseline in cartilage volume in the index region of the target knee by magnetic resonance imaging at Week 52
timeFrame: Baseline and Week 52
measure: Number of participants with Adverse Events
timeFrame: From start of treatment until study completion (approximately 14 months)
Secondary outcomes:
measure: RHH646 plasma concentrations
timeFrame: Baseline, up to End of Study visit (approximately month 13)
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Sugar Land
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Gandrup
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: A Coruna
Study officials:
References: