A Study to Investigate PORT-77 Oral Dosing Compared With Placebo in Participants With Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP)

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).

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:

• 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.

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