A Phase 1/2a, Multicenter, Randomized, Controlled, Single-Blind, Dose-Finding Study to Evaluate the Safety and Efficacy of Cryopreserved Devitalized Adipose Tissue Allograft (BRC-OA) for Pain Treatment in Subjects With Mild to Severe Osteoarthritis (OA) of the Knee
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 13
- 主要终点
- Primary Efficacy Outcome Measure
研究概览
简要总结
The purpose of this study is to evaluate the safety profile of BRC-OA for pain treatment in patients with mild to severe OA of the knee, focusing particularly on two distinct doses. Alongside safety assessments, the study also aims to investigate the initial efficacy of BRC-OA in treating pain among these patients. The study product is a cryopreserved devitalized adipose tissue allograft (BRC-OA). BRC-OA is composed of a devitalized human adipose particulate that retains the inherent properties of adipose such as tissue architecture, extracellular matrix, and signaling molecules.
详细描述
The study will be conducted in two parts:
- Part 1 (Safety Evaluation phase) - without control arm
- Part 2 (Randomized Controlled phase) - with control arm
In Part 1, six subjects will be treated with a 7-day staggering interval between each subject's enrollment. The initial 3 subjects will receive a 2 mL dose of BRCOA, and if deemed safe and well-tolerated by the investigator, the next 3 subjects will receive an 8 mL dose, also following a 7-day staggering interval to assess safety and tolerability. Once both dose levels (2 mL and 8 mL) are confirmed to be safe and tolerable, the study will advance to Part 2. In Part 2, a total of 36 subjects (12 subjects per arm) will be randomized 1:1:1 to three parallel arms to be administered via intraarticular injection of 2 mL or 8 mL of BRC-OA, or 2 mL of normal saline (control).
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females 18-80 years of age, inclusive
- •Diagnosis of OA in one or both knees supported by documentation of clinical and radiographic findings(KL Grades 2-4) up to 6 months prior to screening:
- •Diagnosis of degenerative or post-traumatic OA of the knee supported by documentation of clinical and radiographic findings up to 6 months prior to screening
- •Degenerative meniscal tears allowed as long as there are no pending surgeries
- •Flexion Contraction and Valgus/Varus deformity allowed if < 10 degrees
- •Subject must have tried for at least 3 months and failed on at least two of the following pharmacological standard of care therapies in the past 12 months:
- •Acetaminophen
- •NSAID (e.g., ibuprofen, naproxen)
- •Opioid (e.g., tramadol)
- •Topical NSAID (e.g., diclofenac gel)
- •Intra-articular injections (e.g., corticosteroids, hyaluronic acid)
- •Subjects knee pain persists for at least 12 weeks prior to screening and does not improve with pain medications (e.g., NSAIDs, acetaminophen, tramadol, etc.) and/or other nonoperative treatment options
- •Index knee WOMAC pain subscale score of ≥ 40 on a normalized/standardized scale of 0 to 100 at screening visit Note: The index knee in subjects with bilateral OA of the knees is the one with worse pain with walking. Where both knees have equal pain with walking, then the knee on the subject's dominant side will be designated the index knee.
排除标准
- •BMI greater than 40 kg/m2
- •Previous IA injections (e.g., corticosteroid, hyaluronic acid (HA), platelet rich plasma (PRP), etc.) into the index knee within 3 months prior to screening
- •Prior Partial Joint Replacement (PJR) or Total Joint Replacement (TJR) of one or both knees
- •Knee surgery in the previous 6 months prior to enrollment and/or planned knee surgery during the study
- •Symptomatic OA of the hips, spine, or ankle that would interfere with the evaluation of the treated knee
- •Rapidly progressing osteoarthritis (RPOA)
- •Prior cartilage transplants in the index knee
- •Subjects who are actively treated with oral anticoagulants or heparin therapy (treatment such as low dose Aspirin and Plavix are allowed)
- •Current therapy with any immunosuppressive therapy, including corticosteroids (> 5mg/day of prednisone)
- •Any method of medical marijuana use containing THC or CBD, including smoke or vaporized spray inhalation, pills or liquids, edible foods, topical applications, etc.
- •Clinically significant intercurrent illness, medical condition, non-knee pain, or medical history that could jeopardize the patient safety, limit participation, or compromise interpretation of data derived from the patient; this includes neurological or mental illness, human immunodeficiency virus, fibromyalgia, complex regional pain syndrome, or any active infection - including hepatitis B or C
- •Active alcohol or substance use disorder, or any other reason that would make it unlikely for the patient to comply with study procedures
- •Females who are lactating or pregnant (positive pregnancy test for females of childbearing potential at screening Females of childbearing potential must be willing to use an acceptable method of contraception from screening up until 90 days after study drug injection administration Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, patch, injectable, depot, or vaginal) in conjunction with a barrier method (e.g., diaphragm, cervical cap, condom, spermicide, or sponge), or female subject/partner's use of an implantable device (implantable rod or intrauterine device)
- •Subject has known allergy to any components of BRC-OA
- •Subject has received an investigational product within 3 months before screening
- •Any medical condition, which in the opinion of the clinical investigator, would interfere with the treatment or outcome of the patient
研究组 & 干预措施
Part 2 - 2 mL of Normal Saline via intra-articular injection
干预措施: Normal Saline (Placebo) (Other)
Part 1 - 2 mL of BRC-OA via intra-articular injection
干预措施: Cryopreserved Devitalized Adipose Tissue Allograft (Biological)
Part 1 - 8 mL of BRC-OA via intra-articular injection
干预措施: Cryopreserved Devitalized Adipose Tissue Allograft (Biological)
Part 2 - 2 mL of BRC-OA via intra-articular injection
干预措施: Cryopreserved Devitalized Adipose Tissue Allograft (Biological)
Part 2 - 8 mL of BRC-OA via intra-articular injection
干预措施: Cryopreserved Devitalized Adipose Tissue Allograft (Biological)
结局指标
主要结局
Primary Efficacy Outcome Measure
时间窗: From Baseline and 3 months
• WOMAC VAS Pain Scale - WOMAC (Western Ontario and McMaster Universities Arthritis Index) pain subscale consists of 5 individual questions. The VAS score is determined by measuring in millimeters from the left-hand end of the line to the point that the patient marks (0-100 mm) for 5 questions \[0 represents no knee pain, and 100 represents extreme knee pain\]. The results for each question are summed to calculate the total WOMAC pain subscale score ranging from a total of 0 to 500. The total WOMAC pain subscale score will be normalized/standardized on a scale from 0 to 100. A negative number for the change from baseline indicates a reduction in pain.
Primary Safety Outcome Measures
时间窗: From Baseline to 6 months
• Incidence and severity of local and systemic treatment-emergent adverse events (TEAEs) and SAEs
次要结局
- Secondary Efficacy Outcome Measures(Baseline to 6 months)