A Phase 1/2a Randomized, Double-Blind Placebo-controlled Study of Intra-articular Allocetra in Knee Osteoarthritis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 160
- 试验地点
- 12
- 主要终点
- Treatment-emergent adverse events and Serious adverse events following Allocetra-OTS injection
研究概览
简要总结
This is a double blind, randomized,multi-center study to evaluate the safety and efficacy of intra-articular administration of Allocetra compared to placebo in patients with symptomatic knee osteoarthritis.
详细描述
Knee osteoarthritis is a degenerative disease driven by physical breakdown of the joint cartilage, together with a chronic inflammation within the knee space. Over time, many patients will develop worsening pain in the joint and functional impairment, which may ultimately require knee replacement.
Allocetra is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state.
This Phase 1/2a study is comprised of an open-label safety run-in stage to characterize safety and tolerability of repeated injections of Allocetra to a target knee , followed by a double-blind randomized stage to evaluate the safety and efficacy of Allocetra repeated injections to the target knee compared to placebo, in moderate to severe knee osteoarthritis patients. Patients in both stages will be followed for up to a year following last treatment. the last treatment.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 45 - 80 years.
- •Chronic osteoarthritis of index knee with knee-related joint pain
- •Radiographic evidence of knee osteoarthritis of K-L Grade 2 or 3 in the index knee.
- •Knee pain assessed daily over a period of 7 days during the screening period and following wash-out of pain medications
- •Patients with chronic knee pain for at least 3 months who have failed to respond adequately to conventional therapy.
- •Willing to abstain from other intra-articular treatments and adhere to the protocol restrictions for concomitant medications and therapies during the study.
- •Women of childbearing potential and all men must agree to use 2 methods of an adequate contraception prior to study entry and for the duration of study participation through 4 weeks following IP administration.
排除标准
- •Wheelchair bound.
- •Immunosuppressive therapy
- •Any known current or prior tumor of the index knee.
- •Any known history or current intra-articular or osseous infection of the index knee.
- •Any evidence of clinically significant active infection
- •Any known history of inflammatory arthropathy or crystal-deposition arthropathy
- •Any known severe systemic cartilage and/or bone disorder, such as, but not limited to, chondrodysplasia, osteogenesis imperfecta.
- •Body Mass Index (BMI) >
- •Any major surgical cartilage treatment within 6 months
- •Any ligamentous repair or malalignment correction in the index knee within 6 months
- •Major injury to the index knee, such as torn ligament or severe sprain within 6 months
- •Clinically relevant knee instability of the index knee
- •Severe hip osteoarthritis ipsilateral to the index knee.
- •Clinically significant widespread pain syndromes, e.g., fibromyalgia, long COVID syndrome.
- •Known coagulopathy, or use of anticoagulation medication or antiaggregant medication;.
- •certain tumors, severe cardiac, respiratory or hematologic diseases as defined in the protocol
研究组 & 干预措施
Safety run-in phase - Allocetra increasing dose
An open-label dose escalation phase to characterize the safety and tolerability of Allocetra injections to the knee in different doses and select the Allocetra dose and regimen for the randomized phase.
干预措施: Allocetra (Drug)
Randomization phase - Placebo.
Three intra-articular injections of placebo into the index knee.
干预措施: Placebo (Other)
Randomization phase - Allocetra
Three intra-articular injections of Allocetra at a selected dose, into the index knee.
干预措施: Allocetra (Drug)
结局指标
主要结局
Treatment-emergent adverse events and Serious adverse events following Allocetra-OTS injection
时间窗: 7 months following Day 0
Number and severity of adverse events (AEs), serious adverse events (SAEs) and treatment disruptions/ discontinuations throughout the study from Day 0 and up to 6 months following the last injection
次要结局
- Change from baseline in WOMAC total score.(4 months, 7 months and 13 months following Day 0.)
- Change in quality of life- Euro Quality of Life-5-dimension (EQ-5D) questionnaire(4 months, 7 months and 13 months following Day 0.)
- Weekly average of knee pain.(4 months and 7 months following Day 0.)