Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP

Study Overview
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Brief Summary
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This is an open-label, long-term extension study to investigate the safety, tolerability and efficacy of DISC-1459 in participants with EPP.

Official Title
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An Open-Label, Long-Term Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with diagnosis of EPP who are participating (or who have participated) in a prior Disc Medicine bitopertin study and who have completed the randomized treatment phase and End-of-Study visit Aged ≥12 years upon study consent Body weight ≥32 kg for participants <18 years of age and BMI ≥18.5 kg/m2 for adult participants Exclusion Criteria: Participants who have an ongoing SAE from a clinical study that is assessed by the investigator as related to bitopertin Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgement of the Investigator or Sponsor, would put the participant at unacceptable risk or otherwise preclude participation 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 Planned treatment with afamelanotide or dersimelagon during the study Planned use of any drugs or herbal remedies known to be strong inhibitors or inducers of cytochrome p450 (CYP)3A4 enzymes throughout the study If female, pregnant, or breastfeeding Participation in any other clinical protocol or investigational trial, other than Disc Medicine bitopertin trials, that involves administration of experimental therapy and/or therapeutic devices within 30 days of Day 1 Score of PHQ-8 ≥10 at screening or any response of yes on the C-SSRS Grapefruit/Seville orange and products containing these for 14 days prior to first dose of study drug and throughout the stud

Ages Eligible for Study
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Minimum Age: 12 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DISC-1459 Oral Dose Level 1<br>Oral dose, once a day | Drug: DISC-1459<br>* DISC-1459 dose level 1<br>* Other names: RO4917838;|
| Experimental: DISC-1459 Oral Dose Level 2<br>Oral dose, once a day | Drug: DISC-1459<br>* DISC-1459 dose level 2<br>* Other names: RO4917838;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events |  | up to 5 Years | 
| Incidence of clinically abnormal vital signs |  | up to 5 Years | 
| Incidence of clinically abnormal physical exam |  | up to 5 Years | 
| Incidence of abnormal laboratory test results |  | up to 5 Years | 
| Assessment of Patient Health Questionnaire (PHQ-8) | The Patient Health Questionnaire (PHQ-8), an 8-item participant-report measure for screening for depression and for establishing depression severity. The total score ranges from 0-24, with a higher score indicating greater depression symptom severity. | up to 5 Years | 
| Assessment of C-SSRS | The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. | up to 5 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in daily daylight tolerance, as assessed by total hours spent in the sunlight without pain and average time to first prodromal syndrome in sunlight |  | up to 5 Years | 
| Change from baseline in whole blood metal-free PPIX levels |  | up to 5 Years | 
| Plasma Bitopertin Concentrations |  | up to 5 Years | 

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