Summary
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
Detailed Description
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).
Eligibility Criteria
Age Range: 12 years to No maximum
Inclusion Criteria:
* 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:
1. For participants aged 12 to \<18 years: body weight ≥32 kg
2. 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.
Exclusion Criteria:
* 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 1.
* Known hypersensitivity to PORT-77 or excipients
* Female who has a positive pregnancy test at Screening or Day 1 or is breastfeeding