A Phase 1/2 Randomized, Saline-Controlled, Single-Blind, Multiple Ascending Dose, Dose-Escalation, Multi-Center Trial of PTR-01 in Adult Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
Protocol PTR-01-001 is a Phase 1/2 study of PTR-01.
The study is divided into an up to 4-week Screening Period, a 10-week Treatment Period and an 8-week Follow-up Period.
Cohorts 1, 2, 3 and 4 will consist of 2, 4, 3 and 3 patients respectively. Each cohort will consist of patients divided into two groups (Group 1 and Group 2) randomized in a 1:1 ratio. Patients in Group 1 will receive three doses of active drug followed by 3 doses of saline control. Patients in Group 2 will receive three doses of saline control followed by 3 doses of active drug.
Cohort 1 patients randomized to Group 1 will receive 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg followed by 3 doses of saline control for a total of 6 doses. Cohort 1 patients randomized to Group 2 will receive 3 doses of saline control followed by 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg for a total of 6 doses.
详细描述
Protocol PTR-01-001 is a saline-controlled, single and repeat dose, dose-escalation, crossover study designed to determine the safety, tolerability, tissue kinetics, pharmacodynamics and preliminary efficacy of PTR 01.
The study is divided into three periods: an up to 4-week Screening Period, a 10-week Treatment Period and an 8-week Follow-up Period. During the Screening Period and Follow-up Period there will be no study drug treatment.
During the Treatment Period a total of 3 doses of PTR-01 and 3 doses of saline control will be administered to patients for a total of 6 doses over a 10-week period in three cohorts dosed at 0.1, 0.3, 1.0 and 3.0 mg/kg (active drug). Twelve patients with a diagnosis of RDEB and a history of at least one chronic wound will be enrolled. Those patients who do not have documentation of genetic analysis and IF staining will have blood for genetic analysis and a biopsy for IF staining prior to enrollment (both required).
Cohorts 1, 2, 3 and 4 will consist of 2, 4, 3 and 3 patients respectively. Each cohort will consist of patients divided into two groups (Group 1 and Group 2) randomized in a 1:1 ratio. Patients will receive doses 2 weeks apart. Patients in Group 1 will receive three doses of active drug followed by 3 doses of saline control. Patients in Group 2 will receive three doses of saline control followed by 3 doses of active drug. This cross-over design will yield a total of 14 patients all of whom will receive active drug and saline control.
Prior to randomization, patients will complete a Screening Period to assess the extent and impact of skin disease involvement and the chronicity of at least one wound. Only patients who meet all of the eligibility criteria will be randomized for treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Single-blind
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be at least 16 years of age.
- •Has signed the current approved informed consent form.
- •Has a diagnosis of RDEB based on genetic analysis and consistent with a recessive inheritance pattern.
- •Has deficient C7 staining at the dermal-epidermal junction (DEJ) by IF.
- •Has at least 1 unhealed wound 10-200 cm2 for at least 6 weeks at the Screening Visit.
- •Agrees to use contraception as follows:
- •For women of childbearing potential (WOCBP) agrees to use highly effective contraceptive (including abstinence) methods from Screening, through the study, and for at least 10 weeks after the last dose of study drug. Non-childbearing potential is defined as a female who meets either of the following criteria: age ≥50 years and no menses for at least 1 year or documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy (see Section 7.4.1.2 for details on the definition of non-childbearing potential).
- •For males, agrees to use a condom with any WOCBP sexual partner from Day 1 of study treatment, through the study, and at least 10 weeks after the last dose of study drug.
- •Be willing and able to comply with this protocol.
排除标准
- •Has known systemic hypersensitivity to any of the inactive ingredients in PTR-
- •Is pregnant or nursing.
- •Has received in the last six months any investigational gene therapy product or in the last three months any non-gene therapy investigational products.
- •Is anticipated to receive new regimens of antibiotics or other anti-infectives during the trial.
- •Has any other medical or personal condition that, in the opinion of the Investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical study.
研究组 & 干预措施
PTR-01 0.1 mg/kg
Three intravenous infusions of PTR-01 at 0.1 mg/kg with doses 2 weeks apart.
干预措施: PTR-01 (Drug)
PTR-01 0.3 mg/kg
Three intravenous infusions of PTR-01 at 0.3 mg/kg with doses 2 weeks apart.
干预措施: PTR-01 (Drug)
PTR-01 1.0 mg/kg
Three intravenous infusions of PTR-01 at 1.0 mg/kg with doses 2 weeks apart.
干预措施: PTR-01 (Drug)
Normal Saline
Saline control to mimic PTR-01.
干预措施: Normal saline (Drug)
PTR-01 3.0 mg/kg
Three intravenous infusions of PTR-01 at 3.0 mg/kg with doses 2 weeks apart.
干预措施: PTR-01 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: Up to Day 127
The primary endpoint of this study is safety and tolerability, as assessed by treatment-emergent adverse events, infusion-associated reactions (IAR) and immunogenicity
次要结局
- To measure the peak serum concentration (Cmax) of PTR-01(Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose)
- To measure the time to peak concentration (Tmax) of PTR-01(Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose)
- To measure the area under the curve (AUC) of PTR-01(Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose)
- To measure the clearance of PTR-01(Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose)
- To measure the half-life (t1/2) of PTR-01(Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose)
- Change from Baseline in rC7(Screening and Day 127)
- Change from Baseline in anchoring fibrils(Screening and Day 127)
- Duration of rC7 residence in tissue(Screening and Day 127)