Erythropoietic Protoporphyria (EPP)Phase 2/3PATHWAYNCT07820085
A Study to Investigate PORT-77 Oral Dosing Compared With Placebo in Participants With Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP)
A Phase 2/3 study testing PORT-77 in people with Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP), run by Portal Therapeutics, Inc. at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Erythropoietic Protoporphyria (EPP), X-Linked Protoporphyria (XLP), EPP2
- What is being tested?
- PORT-77
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 225 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2026to Sep 2029
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Investigative Site
Cincinnati, Ohio, 43215
Site Contact
- Recruiting
Investigative Site
Huntington Beach, California, 92647
Site Contact
About this study
Official title: 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
Read the 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).
- Being tested
- PORT-77, Placebo
- Keywords
- PORT-77, EPP, X-linked protoporphyria, Erythropoietic Protoporphyria, XLP, EPP2
- Medical subject headings
- Protoporphyria, Erythropoietic, Protoporphyria, Erythropoietic, X-Linked Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PORT-77Drug
Oral tablets
PlaceboDrug
Oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Phase 2b (Treatment Group 1) | Experimental | PORT-77 Dose 1 Receives: Drug: PORT-77 |
| Phase 2b (Treatment Group 2) | Experimental | PORT-77 Dose 2 Receives: Drug: PORT-77 |
| Phase 2b (Treatment Group 3) | Placebo comparator | Placebo Receives: Drug: Placebo |
| Phase 3 (Treatment Group 1) | Experimental | PORT-77 Receives: Drug: PORT-77 |
| Phase 3 (Treatment Group 2) | Placebo comparator | Placebo Receives: Drug: Placebo |
| Phase 3 (Open-Label Extension) | Experimental | PORT-77 Receives: Drug: PORT-77 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma metal-free PPIX concentration change
Characterize the dose-response of PORT-77 on plasma PPIX levels compared to placebo
Measured: 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
Measured: 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
Measured: Part 2 - Day 155 through 182
Secondary outcomes (11)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: Part 1 - Day 1 through 84; Part 2 - through Day 182
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2026
- Study startSep 2026 (estimated)
- Primary completionMar 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Erythropoietic Protoporphyria (EPP)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 225 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Portal Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Portal Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07820085
- Sponsor's protocol ID
- PORT-77-202
- Other IDs
- 2026-525555-86
- Acronym
- PATHWAY
- Status last verified
- Sep 2026
- First submitted
- 25 Aug 2026
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07820085
- Acronym / sponsor ID
- PATHWAY / PORT-77-202
- Keywords
- PORT-77, EPP, X-linked protoporphyria, Erythropoietic Protoporphyria, XLP, EPP2
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 225 participants (estimated)
- Lead sponsor
- Portal Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2026 (estimated)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 15 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 2b (Treatment Group 1) | Experimental | Drug: PORT-77PORT-77 Dose 1 |
| Phase 2b (Treatment Group 2) | Experimental | Drug: PORT-77PORT-77 Dose 2 |
| Phase 2b (Treatment Group 3) | Placebo comparator | Drug: PlaceboPlacebo |
| Phase 3 (Treatment Group 1) | Experimental | Drug: PORT-77PORT-77 |
| Phase 3 (Treatment Group 2) | Placebo comparator | Drug: PlaceboPlacebo |
| Phase 3 (Open-Label Extension) | Experimental | Drug: PORT-77PORT-77 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PORT-77Oral tablets | Drug | Phase 2b (Treatment Group 1), Phase 2b (Treatment Group 2), Phase 3 (Open-Label Extension), Phase 3 (Treatment Group 1) |
| PlaceboOral tablets | Drug | Phase 2b (Treatment Group 3), Phase 3 (Treatment Group 2) |
Primary outcome
Plasma metal-free PPIX concentration change
Time frame: 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
Time frame: 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
Time frame: 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
11 secondary outcomes
Average daily time in sunlight without pain
Time frame: Part 1 - Days 57 through 84
Change from baseline in daily time in sunlight before first prodromal symptom
Time frame: Part 1 - Day 1 through Day 84; Part 2 - through Day 182
Cumulative total time in sunlight without pain
Time frame: Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Number and severity of phototoxic reactions
Time frame: Part 1 - Day 1 through 84; Part 2 - through Day 182; through Month 12
Change from baseline in validated QoL scores - PGI-C
Time frame: 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
Time frame: Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Change from baseline in validated QoL scores - SF36
Time frame: Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Change from baseline in validated QoL scores - PedsQL
Time frame: Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12
Area under the curve (AUCtau) of PORT-77
Time frame: Part 1 - Day 1 through 84; Part 2 - through Day 182
Cmax of PORT-77
Time frame: Part 1 - Day 1 through 84; Part 2 - through Day 182
Ctrough of PORT-77
Time frame: Part 1 - Day 1 through 84; Part 2 - through Day 182
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chief Medical Officer study director
Portal Therapeutics, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing PORT-77 in people with Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP), run by Portal Therapeutics, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Portal Therapeutics, Inc. (877-660-6479, Portal.clinical.trials@gondolabio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma metal-free PPIX concentration change (time frame: Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.