A Randomized, Placebo Controlled, Investigator and Participant-blinded Study Investigating Safety, Tolerability, and Efficacy of RHH646 in Participants With Knee Osteoarthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 10
- 主要终点
- Change From Baseline in Cartilage Volume in the Index Region of the Target Knee by MRI
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/m
- •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
排除标准
- •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 >
- •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)
研究组 & 干预措施
Placebo
Matching Placebo was administered orally once per day for a year.
干预措施: Placebo (Drug)
RHH646 75 mg
RHH646 was administered orally once per day for a year.
干预措施: RHH646 (Drug)
结局指标
主要结局
Change From Baseline in Cartilage Volume in the Index Region of the Target Knee by MRI
时间窗: 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)
时间窗: 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.
次要结局
- Pharmacokinetic (PK) Parameter: RHH646 Plasma Concentrations(Baseline (4 hours post dose), Week 4 (pre dose))