Australian Clinical Trials

Broad Health Condition Metabolic and Endocrine

Specific Health ConditionMetabolic disorders

Trial FocusTreatment

Recruitment Details

Recruitment status
Recruiting

Recruitment State
NSW,VIC

Hospital
Royal Melbourne Hospital - City campus - Parkville
Royal Prince Alfred Hospital - Camperdown

Postcode
3050 - Parkville
2050 - Camperdown

Anticipated date of first participant enrolment1/07/2022

Anticipated date of last participant enrolment28/02/2023

Phase of TrialPhase 2

Has the study received ethics approval?Approved

Trial summary

The purpose of this research is to assess the safety, tolerability and effectiveness of bitopertin in patients with EPP and XLP. This will be the first time it has been given to individuals with EPP/XLP.  In this study, up to 22 patients will be enrolled in Australia only.
Erythropoietic protoporphyria and XLP are rare diseases which cause severe light sensitivity. Both are caused by mutations in the genes that produce enzymes of the heme production pathway. These defects lead to abnormally high levels of protoporphyrin IX (PPIX) in red blood cells, which leads to painful reactions when exposed to light. Additionally, PPIX accumulates in the liver and gall bladder and can cause gallstones and liver impairment. 
Current therapies for EPP/XLP are aimed at managing symptoms. At present, none act to reduce the high levels of PPIX in the blood. Increased PPIX is thought to be the underlying cause of the severe and potentially life-threatening effects of EPP/XLP.  Thus, there remains a significant unmet medical need for new therapies which address the underlying causes of the disease. 
Disc Medicine Inc is developing bitopertin, an inhibitor of glycine transporter-1 (GlyT1) as a new treatment for EPP/XLP. 

Key inclusion criteria

1. Aged 18 years or older 
2. Diagnosis of EPP or XLP, based on medical history of FECH or ALAS2 genotyping or by biochemical porphyrin analysis.
3. Body weight greater than or equal to 50 kg.
4. Washout of at least 2 months prior to Screening of afamelanotide or dersimelagon, if applicable.
5. Aspartate aminotransferase (AST) and alanine transaminase (ALT)  less than 2×upper limit of normal (ULN) and total bilirubin less than ULN (unless documented Gilbert syndrome) at Screening. Albumin greater than lower limit of normal (LLN).
6. If male with female sexual partner(s) of childbearing potential, agrees he and partner will use one of the following acceptable methods of birth control during the study and for 30 days after the last study drug dose:
a. abstinence
b. stable hormonal contraceptive or a barrier method (e.g., condom [male or female] or diaphragm)
c. intrauterine device, in place for at least 3 months
d. surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation
7. If female of childbearing potential, defined as prior menarche, no hysterectomy, no bilateral oophorectomy, not postmenopausal (at least 12 months natural, spontaneous amenorrhea), must commit to one of the following methods of acceptable birth control during the study and for 30 days after the last study drug dose:
a. abstinence
b. stable hormonal contraceptive in conjunction with a barrier method (e.g., condom [male or female] or diaphragm)
c. intrauterine device, in place for at least 3 months
8. Negative urine or serum pregnancy test (females of childbearing potential) at Screening (Days -28 to -1) AND Baseline (Day 1), prior to dosing.
9. Able to understand the study aims, procedures, and requirements, and provide written informed consent.
10. Able to comply with all study procedures.

Minimum age18 Years

GenderBoth males and females

Can Healthy volunteers participate? No

Key exclusion criteria

1. Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
2. Other than EPP, an inherited or acquired red cell disease associated with anemia.
3. A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug.
4. History of liver transplantation.
5. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
6. Human immunodeficiency virus (HIV), active Hepatitis B, or C. A positive Hepatitis B result, indicating active disease status, should be discussed between the Investigator and Sponsor prior to enrollment.
7. 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
8. 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.
9. Concurrent or planned treatment with afamelanotide or dersimelagon.
10. Treatment with opioids for any period greater than 7 days in the 2 months prior to screening or anticipated to require opioid use for greater than 7 days at any point during the study.
11. Treatment for anemia, including iron supplementation, in the 2 months prior to Screening.
12. 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
13. Hemoglobin less than 10 g/dL at Screening.
14. If female, pregnant or breastfeeding.
15. Participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices within 30 days of Screening.
16. Grapefruit/Seville orange and food products containing these, for 14 days prior to first dose and throughout the study