An Open-Label, Single Ascending Dose Study to Assess the Safety and Tolerability of FX201 in Patients with Osteoarthritis of the Knee
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 72
- 试验地点
- 6
- 主要终点
- Primary Outcome Measure: Incidence of treatment emergent adverse events after a single intra-articular (IA) injection of FX201 (safety and tolerability)
研究概览
简要总结
This two-part study will be conducted in male and female patients, 30 - 80 years of age with painful OA of the index knee with Kellgren-Lawrence (K-L) Grade 2, 3 or 4.
Part 1 - Single Ascending Dose (SAD) Phase: Up to three ascending doses of FX201 will be tested in cohorts of 5-8 patients. Each patient will only receive one injection of FX201. An independent Data Monitoring Committee (DMC) will review safety and guide the conduct of the study.
Part 2 - Expansion Phase: Up to an additional 35 patients will be enrolled at each dose level reviewed by the DMC. Each patient will only receive one injection of FX201.
详细描述
This two-part study will be conducted in male and female patients, 30 - 80 years of age with painful OA of the index knee with Kellgren-Lawrence (K-L) Grade 2, 3 or 4.
Part 1 - SAD Phase: Up to three ascending doses of FX201 (low dose, mid dose and high dose) will be tested in cohorts of 5-8 patients. Each patient will only receive one injection of FX201. A maximum of 24 patients will be enrolled (range 15 to 24).
When a minimum of 4 weeks have elapsed since the last patient of the current cohort has been treated, all safety data will be collected and reviewed by an independent Data Monitoring Committee (DMC). After evaluating cohort safety data, the DMC will evaluate continuing the trial and initiating treatment in the next dosing cohort as well as expanding enrollment in dose level(s).
Part 2 - Expansion Phase: After the DMC has met to review safety data from each Cohort and has recommended expanding dose level(s), enrollment slots for dose levels reviewed by the DMC will be opened. A maximum of 105 patients [up to an additional 35 patients per dose level (up to 20 FX201 alone and up to 15 FX201 with IA methylprednisolone 40 mg/mL pre-treatment)].
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written consent to participate in the study
- •Male or female 30 to 80 years of age, inclusive, on the day of enrollment (Day 1)
- •Body mass index (BMI) ≤ 40 kilograms per meters squared (kg/m2)
- •Clinical diagnosis of OA of the knee on the American College of Rheumatology criteria (Altman, 1986) with radiologic evidence of OA (K-L Grade 2 or 3 for SAD Phase Cohort A and K-L Grade 2, 3 or 4 for SAD Phase Cohorts B and C and the Expansion Phase) at the index joint at the screening visit
- •Moderate pain in the index joint
- •Failed two or more types of conservative therapy for index knee osteoarthritis (e.g., structured exercise programs, topical or oral non-steroidal anti-inflammatory therapies); or failed one prior type of conservative therapy and at least one prior index knee IA treatment (corticosteroid or hyaluronic acid)
- •Sexually active females and males agree to use highly effective methods of contraception
排除标准
- •Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease
- •History of or current infection in the index knee joint
- •Inability to undergo Magnetic Resonance Imaging (MRI) due to presence of surgical hardware or other foreign body in the index knee
- •Unstable index knee joint (e.g., torn anterior cruciate ligament, etc.) within 12 months of Screening
- •Any IA drug/biologic use within 6 months of Screening or 5 half-lives (whichever is longer) (e.g., IA corticosteroid, IA hyaluronic acid, platelet rich plasma injection, stem cells, prolotherapy and amniotic fluid injection, etc.)
- •Cold or radiofrequency nerve ablation of the index knee within 12 months of Screening
- •Arthroscopic or open surgery on the index knee within 12 months of Screening or planned/anticipated surgery on the index knee for the study period
- •Anticipated major surgery during the study period
- •Laboratory values that meet exclusion criteria
- •ECG abnormality at Screening or Baseline judged clinically significant
- •Use of immunomodulators, immunosuppressive, or chemotherapeutic agents within 5 years of Screening
- •Use of any other investigational drug, biologic or device within 3 months of Screening
- •Any systemic or local bacterial or viral infection requiring IV antibiotics or antivirals within 4 weeks of Screening or oral antibiotics or antivirals within 2 weeks of Screening
- •Known allergy or sensitivity to methylprednisolone
- •Any other clinically significant acute or chronic medical conditions (e.g., bleeding disorder) that, in the judgment of the Investigator, would preclude the use of an IA injection or that could compromise patient safety, limit the patient's ability to complete the study, and/or compromise the objectives of the study
- •Note: Other protocol defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Low Dose FX201
Single low dose FX201 injection
干预措施: FX201 (Biological)
Mid Dose FX201
Single mid dose FX201 injection
干预措施: FX201 (Biological)
High Dose FX201
Single high dose FX201 injection
干预措施: FX201 (Biological)
结局指标
主要结局
Primary Outcome Measure: Incidence of treatment emergent adverse events after a single intra-articular (IA) injection of FX201 (safety and tolerability)
时间窗: Baseline to Week 104
Incidence of treatment emergent adverse events after a single intra-articular (IA) injection of FX201
次要结局
- Secondary Outcome Measure: Characterization of the systemic biodistribution of FX201 as seen through the percentage of patients positive for FX201 at Baseline, Day 1, Day 2, Week 1, Week 2, Week 3, and Week 4(Baseline, Day 1, Day 2, Week 1, Week 2, Week 3, Week 4)