Phase 1 Safety Run-in Study and Phase 1b Randomized, Double Blinded, Placebo Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 66
- 试验地点
- 3
- 主要终点
- Combined assessment of function and survival (CAFS)
研究概览
简要总结
Phase 1 Safety Run-in Study of 6 patients followed by Phase 1b Randomized, Double Blind, Placebo Control Trial of CK0803, neurotropic, allogeneic, umbilical cord blood derived T regulatory (Treg) cells in additional 60 patients with Amyotrophic Lateral Sclerosis.
详细描述
CK0803, neurotrophic allogenic T regulatory Cells (Treg), utilizes Cellenkos' proprietary CRANE technology to generate disease specific products. The primary objective of the upcoming phase 1 study is to establish safety and tolerability of multiple doses of CK0803 in ALS patients. The goal of the phase 1b study is to extend safety and establish efficacy of CK0803 in ALS using the combined assessment of function and survival (CAFS) that ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score.
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)
盲法说明
Double Blinded, Placebo Control
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability of the subject or his/her legally authorized representative to provide informed consent.
- •Adult ALS subjects (≥18 years of age)
- •Diagnosis of ALS, according to the Revised El Escorial Criteria for ALS
- •Subjects with disease onset ≤ 5 years
- •Upright (sitting position) Slow Vital Capacity (SVC) as adjusted for sex, age and height ≥ 50% predicted
- •Subjects must have documented ALSFRSR score of 36-45 at baseline.
- •Subjects taking concomitant Riluzole or Edaravone or Albrioza at study entry must be on a stable dose for ≥ 30 days prior to the first dose of study treatment (Day 1).
- •Screening values of coagulation parameters including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) should be within normal ranges.
- •Agree to practice highly effective contraception during the study and continue contraception for 90 days after their last dose of study treatment.
排除标准
- •Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol medical monitor is the final arbiter of eligibility.
- •Antiplatelet or anticoagulant therapy within the 14 days prior to Day 1 or anticipated use during the study, including but not limited to daily aspirin including low dose aspirin (defined as ≤ 150 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban
- •Clinically significant low platelet count (defined as < 100,000/mm3), coagulation tests, or laboratory abnormalities that would render a subject unsuitable for inclusion
- •Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
- •Have any other conditions, which, in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study
- •Concurrent participation in any other interventional clinical study
- •Treatment with another investigational drug, biological agent, or device, including, but not limited to sodium phenylbutyrate, within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
- •Treatment of cancer in the last 5 years (except in situ carcinoma of the cervix or basal cell carcinoma)
- •Female subjects who are pregnant or currently breastfeeding
- •Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the subject unsuitable for enrollment.
研究组 & 干预措施
CK0803
CK0803 (cryopreserved, allogeneic, cord blood derived T regulatory cells that express neurotropic homing markers) will be administered intravenously Dose: 100 million Treg cells (fixed dose)
Dose regimen:
- Induction: one infusion every 7 days (+/-3) x 4 doses
- Consolidation: one infusion every 28 days (+/-3) x 5 doses
干预措施: CK0803 (Biological)
Placebo
Excipient
干预措施: Excipient (Other)
结局指标
主要结局
Combined assessment of function and survival (CAFS)
时间窗: 24 weeks
CAFS ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score where score = 0 is worst and score = 48 is best. Each patient's outcome is compared to every other patient's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS score indicates a better group outcome.
Treatment Limiting Toxicity (TLT)
时间窗: 28 days
TLT of CK0803 as assessed by the incidence and severity of AE and SAEs using NCI-CTCAE Version 5.0 criteria. TLT is a primary endpoint for bothe phase 1 safety run-in and phase 1b RCT part
次要结局
- Slow Vital Capacity (SVC)(Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT)
- Nfl CSF(Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT)
- Nfl Serum(Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT12 months)
- Incidence of all cause AEs and SAEs(baseline and at weeks 1, 2, 3, 4, 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at end of treatment (EOT))
- ALS Functional Rating Scale-Revised (ALSFRS-R) Score(Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT)
- Ventilation assistance-free survival (VAFS)(Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT)
- Overall Survival (OS)(24 weeks and 48 weeks from first infusion and/or at EOT)
- Handheld dynamometer (HHD)(Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT)
- Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R)(Each measured at baseline and at weeks 5, 8, 12 and/or 13, 16, 20, 24 and/or 25, 36 and 48 from first infusion and/or at EOT)