EPP2, Erythropoietic Protoporphyria (EPP), X-Linked Protoporphyria (XLP)
Conditions
Keywords
PORT-77, EPP, X-linked protoporphyria, Erythropoietic Protoporphyria, XLP, EPP2
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
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).
Interventions
DRUGPORT-77
Oral tablets
DRUGPlacebo
Oral tablets
Sponsors
Portal Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma metal-free PPIX concentration change | 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 | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average daily time in sunlight without pain | Part 1 - Days 57 through 84 | Assess the effect of different doses of PORT-77 on average daily time in sunlight without pain compared to placebo |
| Change from baseline in daily time in sunlight before first prodromal symptom | Part 1 - Day 1 through Day 84; Part 2 - through Day 182 | Assess the effect of different doses of PORT-77 on average daily time in sunlight before first prodromal symptom compared to placebo |
| Cumulative total time in sunlight without pain | Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12 | Assess the effect of different doses of PORT-77 on cumulative total time in sunlight without pain compared to placebo |
| Number and severity of phototoxic reactions | Part 1 - Day 1 through 84; Part 2 - through Day 182; through Month 12 | Assess the effect of different doses of PORT-77 on the rate and severity of phototoxic reactions compared to placebo |
| 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 | 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. |
| Change from baseline in validated QoL scores - PGI-S | Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12 | 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. |
| Change from baseline in validated QoL scores - SF36 | Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12 | 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. |
| Change from baseline in validated QoL scores - PedsQL | Part 1 - Days 1 through 84; Part 2 - through Day 182; Part 3 - through Month 12 | 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. |
| Area under the curve (AUCtau) of PORT-77 | Part 1 - Day 1 through 84; Part 2 - through Day 182 | Model derived area under the curve of PORT-77 during dosing interval at steady state |
| Cmax of PORT-77 | Part 1 - Day 1 through 84; Part 2 - through Day 182 | Model derived maximal concentration after dosing of PORT-77 at steady state |
| Ctrough of PORT-77 | Part 1 - Day 1 through 84; Part 2 - through Day 182 | Model derived trough concentration after dosing of PORT-77 at steady state |
Countries
United States
Contacts
CONTACTPortal Therapeutics, Inc.
STUDY_DIRECTORChief Medical Officer
Portal Therapeutics, Inc.
Outcome results
None listed