A Phase 2b/3, Quadruple-Blinded, Randomized, Placebo-Controlled Study of PORT-77 Administered Orally to Adults and Adolescents With Erythropoietic Protoporphyria or X-Linked Protoporphyria and an Open-Label Extension
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 225
- 试验地点
- 2
- 主要终点
- Plasma metal-free PPIX concentration change
研究概览
简要总结
PATHWAY is a Phase 2b/3 clinical study with an Open-Label Extension (OLE). It tests PORT-77 in patients with EPP, EPP2, and XLP.
The study has three parts:
Part 1: Phase 2b
- Find the right dose of PORT-77 to lower PPIX levels in the blood
- Test if PORT-77 lowers PPIX levels better than placebo
- Check the safety of each dose
Part 2: Phase 3
- Test if PORT-77 lowers PPIX levels better than placebo
- Test if PORT-77 increases the amount of time patients spend in sunlight each day without pain compared to placebo
- Check the safety of PORT-77
Part 3: Open-Label Extension (OLE)
- Test the long-term effect of PORT-77 on PPIX levels and time in sun
- Monitor long-term safety
详细描述
PATHWAY is a Phase 2b/3, multiregional, multicenter clinical study of PORT-77 in adults and adolescents with EPP or XLP. The study consists of 3 parts: Part 1 (Phase 2b), Part 2 (Phase 3), and Part 3 (OLE).
Part 1 and Part 2 are randomized, quadruple-blinded, placebo-controlled studies. Part 1 is a Phase 2b study evaluating the safety, tolerability, and preliminary efficacy of 2 dose levels of PORT-77. Part 2 is a Phase 3 study designed to confirm the efficacy of the selected PORT-77 dose and to further characterize safety in a larger cohort. All participants who complete Part 1 or Part 2 of the study will have the opportunity to enroll in Part 3 (OLE).
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)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 12 years or older.
- •Clinical history of EPP, XLP, or EPP2 supported by genetic confirmation or historical laboratory test results
- •History of consistent, non-painful prodrome within approximately 45 minutes of sunlight exposure and prior to phototoxic attacks
- •Demonstrates ≥85% compliance with daily symptom diary during run-in period.
- •Body weight or BMI at Screening as follows:
- •For participants aged 12 to <18 years: body weight ≥32 kg
- •For participants aged ≥18 years: BMI ≥18.5 kg/m2
- •AST and ALT <3 × ULN and total bilirubin <2 × ULN (unless documented Gilbert syndrome) at Screening
- •Willing and able to provide informed consent and/or assent for the study.
- •Willing and able to comply with study visits, study procedures, and contraception guidance
- •Intends to remain in the same approximate geographic latitude for the duration of the placebo-controlled period, with no more than 14 days spent outside this region.
排除标准
- •Diagnosis of another porphyria or another photodermatosis that may confound the evaluation of PORT-77
- •Any evidence of clinically significant organ dysfunction or any clinically significant deviation from normal in the clinical or laboratory assessments
- •Major surgery within 8 weeks before Screening, incomplete recovery from any previous surgery, or major surgery planned to occur during the study
- •History of, or anticipated need for, liver transplantation or history of bone marrow transplantation
- •Active infection with hepatitis B or C
- •Unable to swallow tablets or has a disease that significantly affects gastrointestinal function
- •Any other disease, condition, or circumstance that, at the discretion of the Investigator or Sponsor, would interfere with the evaluation of PORT-77 or study participation, or would make study participation not in the best interest of the participant
- •History of drug or alcohol abuse within the last 12 months, or current or planned use of prohibited or illegal substances
- •Has taken any medication, vitamin, or supplement that alters sensitivity to light exposure (eg, afamelanotide, melanotan, beta carotene, dersimelagon) within 90 days of Day 1; or has taken bitopertin within 120 days of Day 1; or has taken iron within 30 days of Day 1
- •Drugs or supplements that may impact or be impacted by PORT-77
- •Concurrent or anticipated participation in an interventional clinical trial during the study period.
- •Received another investigational therapy within 5 half-lives, if the half-life is known, or within 30 days, if the half-life is unknown, prior to Day
- •Known hypersensitivity to PORT-77 or excipients
- •Female who has a positive pregnancy test at Screening or Day 1 or is breastfeeding
研究组 & 干预措施
Phase 2b (Treatment Group 3)
Placebo
干预措施: Placebo (Drug)
Phase 3 (Treatment Group 2)
Placebo
干预措施: Placebo (Drug)
Phase 2b (Treatment Group 1)
PORT-77 Dose 1
干预措施: PORT-77 (Drug)
Phase 2b (Treatment Group 2)
PORT-77 Dose 2
干预措施: PORT-77 (Drug)
Phase 3 (Treatment Group 1)
PORT-77
干预措施: PORT-77 (Drug)
Phase 3 (Open-Label Extension)
PORT-77
干预措施: PORT-77 (Drug)
结局指标
主要结局
Plasma metal-free PPIX concentration change
时间窗: Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Characterize the dose-response of PORT-77 on plasma PPIX levels compared to placebo
Adverse Events
时间窗: Part 1 - Day 1 through Day 84; Part 2 - through Day 182; Part 3 - through Month 12
Evaluate safety and tolerability of each dose of PORT-77 over the course of the study
Average daily time in sunlight without pain
时间窗: Part 2 - Day 155 through 182
Assess the effect of different doses of PORT-77 on average daily time in sunlight without pain compared to placebo
次要结局
- Average daily time in sunlight without pain(Part 1 - Days 57 through 84)
- Change from baseline in daily time in sunlight before first prodromal symptom(Part 1 - Day 1 through Day 84; Part 2 - through Day 182)
- Cumulative total time in sunlight without pain(Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12)
- Number and severity of phototoxic reactions(Part 1 - Day 1 through 84; Part 2 - through Day 182; through Month 12)
- Change from baseline in validated QoL scores - PGI-C(Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12)
- Change from baseline in validated QoL scores - PGI-S(Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12)
- Change from baseline in validated QoL scores - SF36(Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12)
- Change from baseline in validated QoL scores - PedsQL(Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12)
- Area under the curve (AUCtau) of PORT-77(Part 1 - Day 1 through 84; Part 2 - through Day 182)
- Cmax of PORT-77(Part 1 - Day 1 through 84; Part 2 - through Day 182)
- Ctrough of PORT-77(Part 1 - Day 1 through 84; Part 2 - through Day 182)