Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP

Study Overview
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Brief Summary
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This is a Phase 2, multi-center, double-blind, placebo-controlled, parallel group study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentration change in participants with EPP. Participants may roll over to an open label extension portion after completing the double-blind treatment period.

Official Title
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(AURORA) A Randomized, Double-blind, Placebo-Controlled Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and Protoporphyrin IX (PPIX) Concentrations in Participants With Erythropoietic Protoporphyria (EPP)

Conditions
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Erythropoietic Protoporphyria

Intervention / Treatment
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* Drug: DISC-1459
* Drug: DISC-1459
* Drug: Placebo
* Drug: DISC-1459


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older at the time of signing the informed consent form (ICF). Diagnosis of EPP, based on medical history by ferrochelatase ( FECH) genotyping or by biochemical porphyrin analysis. Body weight ≥50 kg. Washout of at least 2 months prior to Screening of afamelanotide and dersimelagon, if applicable. Aspartate aminotransferase (AST) and alanine transaminase (ALT) <2× upper limit of normal (ULN) and total bilirubin <ULN (unless documented Gilbert syndrome) at Screening. Albumin >lower limit of normal (LLN). Exclusion Criteria: Medical History: Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery. Other than EPP, an inherited or acquired red cell disease associated with anemia. A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug. History of liver transplantation. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator. Human immunodeficiency virus (HIV), active Hepatitis B, or C. Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgment of the Investigator or Sponsor, would put the participant at unacceptable risk or otherwise preclude the participant from participating in the study Condition or concomitant medication that would confound the ability to interpret clinical, clinical laboratory, or participant diary data, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months. Treatment History: Concurrent or planned treatment with afamelanotide or dersimelagon during the study period. Treatment with opioids for any period >7 days in the 2 months prior to screening or anticipated to require opioid use for >7 days at any point during the study. New treatment for anemia, including initiation of iron supplementation, in the 2 months prior to Screening. Current or planned use of any drugs or herbal remedies known to be strong inhibitors or inducers of CYP3A4 enzymes for 28 days prior to the first dose and throughout the study. Laboratory Exclusions: Hemoglobin <10 g/dL at Screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral dose, once a day for 120 days<br>|
| Experimental: DISC-1459 oral dose level 1<br> | Drug: DISC-1459<br>* Oral dose level 1, once a day for 120 days<br>* Other names: RO4917838;|
| Experimental: DISC-1459 oral dose level 2<br> | Drug: DISC-1459<br>* Oral dose level 2, once a day for 120 days<br>* Other names: RO4917838;|
| Experimental: Open-Label Extension (optional)<br> | Drug: DISC-1459<br>* Oral dose level 1, once a day for up to 8 months<br>* Other names: RO4917838;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in whole blood metal-free PPIX levels |  | 121 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total hours of sunlight exposure to skin on days with no pain from 1000 to 1800 hours (10:00am to 6:00pm) |  | 121 days | 
| Daily sunlight exposure time (minutes) to first prodromal symptom (burning, tingling, itching, or stinging) associated with sunlight exposure between 1 hour post-sunrise and 1 hour pre-sunset |  | 121 days | 
| Pain intensity of phototoxic reactions according to a Likert scale (0-10) |  | 121 days | 
| Incidence of treatment-emergent adverse events |  | 121 days | 
| Erythrocyte total PPIX concentrations |  | 121 days | 
| Plasma total PPIX concentrations |  | 121 days | 
| Whole blood total PPIX concentrations |  | 121 days | 
| Plasma bitopertin concentrations |  | 121 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EPP, DISC-1459, RO4917838, porphyria