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

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

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

Study Overview

• Status: Recruiting
• Conditions: Erythropoietic Protoporphyria (EPP); X-Linked Protoporphyria (XLP); EPP2
• Intervention / Treatment: Drug: Placebo; Drug: PORT-77

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).

• Study Type: Interventional
• Enrollment (Estimated): 225
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Portal Therapeutics, Inc.; Phone Number: 877-660-6479; Email: Portal.clinical.trials@gondolabio.com

Study Locations

• United States
  • California
    • Huntington Beach, California, United States, 92647
      • Recruiting
      • Investigative Site
      • Contact: Site Contact
  • Ohio
    • Cincinnati, Ohio, United States, 43215
      • Recruiting
      • Investigative Site
      • Contact: Site Contact

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2b (Treatment Group 1); PORT-77 Dose 1	Drug: PORT-77; Oral tablets
Experimental: Phase 2b (Treatment Group 2); PORT-77 Dose 2	Drug: PORT-77; Oral tablets
Placebo Comparator: Phase 2b (Treatment Group 3); Placebo	Drug: Placebo; Oral tablets
Experimental: Phase 3 (Treatment Group 1); PORT-77	Drug: PORT-77; Oral tablets
Placebo Comparator: Phase 3 (Treatment Group 2); Placebo	Drug: Placebo; Oral tablets
Experimental: Phase 3 (Open-Label Extension); PORT-77	Drug: PORT-77; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 1 - Days 57 through 84
Change from baseline in daily time in sunlight before first prodromal symptom	Assess the effect of different doses of PORT-77 on average daily time in sunlight before first prodromal symptom compared to placebo	Part 1 - Day 1 through Day 84; Part 2 - through Day 182
Cumulative total time in sunlight without pain	Assess the effect of different doses of PORT-77 on cumulative total time in sunlight without pain compared to placebo	Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Number and severity of phototoxic reactions	Assess the effect of different doses of PORT-77 on the rate and severity of phototoxic reactions compared to placebo	Part 1 - Day 1 through 84; Part 2 - through Day 182; through Month 12
Change from baseline in validated QoL scores - PGI-C	Evaluate the effect of PORT-77 on the Patient Global Impressions - Change in clinical status (PGI-C) in adults compared to placebo. The PGI-C measures Change in clinical status. Higher numerical scores (1-7) in PGI-C indicate worsening of clinical status.	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	Evaluate the effect of PORT-77 on the Patient Global Impressions - Severity of clinical status. The PGI-S measures Severity of clinical status. Higher numerical scores in PGI-S (1-5) indicate greater symptom severity.	Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Change from baseline in validated QoL scores - SF36	Evaluate the effect of PORT-77 on the Short Form 36 Health Survey (SF-36) in adults compared to placebo. The SF-36 covers 36 individual items that evaluate functional health and well-being. It produces eight health domain scores and two summary component scores (Physical Component Summary and Mental Component Summary) where higher values (0-100) represent better health.	Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Change from baseline in validated QoL scores - PedsQL	Evaluate the effect of PORT-77 on the Pediatric Quality of Life Inventory (PedsQL) in adolescents compared to placebo. The (PedsQL) evaluates four main domains: physical functioning, emotional functioning, social functioning, and school functioning. It uses a 0 to 100 scale where higher scores show a better health-related quality of life.	Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Area under the curve (AUCtau) of PORT-77	Model derived area under the curve of PORT-77 during dosing interval at steady state	Part 1 - Day 1 through 84; Part 2 - through Day 182
Cmax of PORT-77	Model derived maximal concentration after dosing of PORT-77 at steady state	Part 1 - Day 1 through 84; Part 2 - through Day 182
Ctrough of PORT-77	Model derived trough concentration after dosing of PORT-77 at steady state	Part 1 - Day 1 through 84; Part 2 - through Day 182

Collaborators and Investigators

• Sponsor: Portal Therapeutics, Inc.
• Investigators: Study Director: Chief Medical Officer, Portal Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: August 25, 2026
• First Submitted That Met QC Criteria: September 10, 2026
• First Posted (Actual): September 15, 2026

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 10, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: EPP; XLP; Erythropoietic Protoporphyria; PORT-77; X-linked protoporphyria; EPP2
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Skin Diseases; Skin Diseases, Genetic; Porphyrias, Hepatic; Porphyrias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Protoporphyria, Erythropoietic; Protoporphyria, Erythropoietic, X-Linked Dominant
• Other Study ID Numbers: PORT-77-202; 2026-525555-86 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No