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

NCT07820085 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PORT-77-2022026-525555-86
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

X-Linked Protoporphyria (XLP); EPP2; Erythropoietic Protoporphyria (EPP)

Keywords

PORT-77; EPP; X-linked protoporphyria; Erythropoietic Protoporphyria; XLP; EPP2

Outcome Measures

Primary Outcomes (3)

• Plasma metal-free PPIX concentration change

  Characterize the dose-response of PORT-77 on plasma PPIX levels compared to placebo

  Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12

• Adverse Events

  Evaluate safety and tolerability of each dose of PORT-77 over the course of the study

  Part 1 - Day 1 through Day 84; Part 2 - through Day 182; Part 3 - through Month 12

• Average daily time in sunlight without pain

  Assess the effect of different doses of PORT-77 on average daily time in sunlight without pain compared to placebo

  Part 2 - Day 155 through 182

Secondary Outcomes (11)

• 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

Study Arms (6)

Phase 2b (Treatment Group 1)

EXPERIMENTAL

PORT-77 Dose 1

Drug: PORT-77

Phase 2b (Treatment Group 2)

EXPERIMENTAL

PORT-77 Dose 2

Drug: PORT-77

Phase 2b (Treatment Group 3)

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Phase 3 (Treatment Group 1)

EXPERIMENTAL

PORT-77

Drug: PORT-77

Phase 3 (Treatment Group 2)

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Phase 3 (Open-Label Extension)

EXPERIMENTAL

PORT-77

Drug: PORT-77

Interventions

PORT-77 DRUG

Oral tablets

Phase 2b (Treatment Group 1); Phase 2b (Treatment Group 2); Phase 3 (Open-Label Extension); Phase 3 (Treatment Group 1)

Placebo DRUG

Oral tablets

Phase 2b (Treatment Group 3); Phase 3 (Treatment Group 2)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Portal Therapeutics, Inc.: lead

Study Sites (2)

Investigative Site

Huntington Beach, California, 92647, United States

RECRUITING

Investigative Site

Cincinnati, Ohio, 43215, United States

RECRUITING

MeSH Terms

Conditions

Protoporphyria, Erythropoietic; Protoporphyria, Erythropoietic, X-Linked Dominant

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Porphyrias; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Chief Medical Officer

  Portal Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Portal Therapeutics, Inc.

CONTACT

877-660-6479; Portal.clinical.trials@gondolabio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2026
• First Posted: September 15, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 15, 2026

Record last verified: 2026-09

Locations

US (2)