E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Erythropoietic Protoporphyria or X-Linked Protoporphyria |
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E.1.1.1 | Medical condition in easily understood language |
Erythropoietic Protoporphyria or X-Linked Protoporphyria |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 24.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015289 |
E.1.2 | Term | Erythropoietic protoporphyria |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of oral dersimelagon. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects provided written informed consent to participate. For adolescent subjects, both adolescent assent and parental consent will be provided. 2. Subjects who complete MT-7117-G01 (complete through Week 58 [Visit 12]) 3. Subjects have a body weight of ≥30 kg. 4. Subjects are willing and able to travel to the study sites for all scheduled visits. 5. In the Investigator’s opinion, subject can understand the nature of the study and any risks involved in participation, and is willing to cooperate and comply with the protocol restrictions and requirements (including travel). 6. Female subjects who are non-lactating and have a negative urine pregnancy test at baseline visit prior to receiving the first dose of study drug. 7. Female subjects of childbearing potential and male subjects with partner of childbearing potential must agree to use 2 effective methods of contraception including barrier method (especially for female subjects, one method must be highly effective method) as described in Section 4.6.1. |
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E.4 | Principal exclusion criteria |
1. History or presence of photodermatoses other than EPP or XLP. 2. Presence or history of any hepatobiliary disease at screening determined as clinically significant by the Investigator after the discussion with the Sponsor Medical Monitor. 3. Subjects with AST, ALT, ALP ≥3.0 × upper limit of normal (ULN) or total bilirubin > 1.5 × ULN at Screening. 4. Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator. 5. History of melanoma. 6. Presence of melanoma and/or lesions suspicious for melanoma at Screening. 7. History of familial melanoma (defined as having 2 or more first-degree relatives, such as parents, sibling and/or child). 8. Presence of squamous cell carcinoma, basal cell carcinoma, or other malignant skin lesions. Any suspicious lesions or nevi will be evaluated. If the suspicious lesion or nevi cannot be resolved through biopsy or excision, the subject will be excluded from the study. 9. History or presence of psychiatric disease judged to be clinically significant by the Investigator and which may interfere with the study evaluation and/or safety of the subjects. 10. Presence of clinically significant acute or chronic renal disease based upon the subject’s medical records including hemodialysis; an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 as calculated by the CKD-EPI creatinine equation (2009) for adults and by the Schwartz creatinine equation for adolescents (2009) (Section 16.2, Appendix 2). MDRD can be used for adults per local recommendations. 11. Presence of any clinically significant disease or laboratory abnormality which, in the opinion of the Investigator, can interfere with the study objectives and/or safety of the subjects. 12. Female subjects who are pregnant, lactating, or intending to become pregnant during the study. 13. Treatment with phototherapy or afamelanotide within 3 months before baseline (Visit 2). 14. Treatment with cimetidine or antioxidant agents at doses which, in the opinion of the Investigator, may affect study endpoints (including but not limited to beta-carotene, cysteine, pyridoxine) within 4 weeks before baseline (Visit 2). 15. Chronic treatment with any scheduled analgesic agents including, but not limited to, opioids and opioid derivatives such as morphine, hydrocodone, oxycodone, fentanyl, or their combination with other unscheduled analgesics or non-steroidal anti-inflammatory drug (Percocet and Vicodin-like prescription drugs) within 4 weeks before baseline (Visit 2). Acute use of scheduled narcotics greater than 3 months prior to baseline, overthe- counter medications (OTCs), such as non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin for analgesia, or prior temporary use of scheduled agents within 3 months of baseline (Visit 2) are not excluded. 16. Treatment with any drugs or supplements which, in the opinion of the Investigator, can interfere with the objectives of the study or safety of the subjects. 17. Previous treatment with any investigational agent other than dersimelagon within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer). 18. Using the following drugs (including but not limited to) within 1 week of baseline (Visit 2): a. Drugs known to be predominantly metabolized by cytochrome P450 (CYP) 3A4 with a narrow therapeutic index for which elevated plasma concentrations are associated with clinical safety concern or significant medical events. b. Drugs that are known substrates of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP)1B1, or OATP1B3 for which elevated plasma concentrations are associated with significant medical events.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Treatment-emergent adverse events (TEAEs) (including serious adverse events [SAEs] and adverse events of special interest [AESIs]). 2. Physical examination. 3. Vital signs (blood pressure, respiratory rate, pulse rate, and body temperature). 4. Clinical laboratory examinations (hematology, coagulation, biochemistry, and urinalysis), including liver function markers (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], direct and total bilirubin). 5. 12-lead electrocardiogram (ECG) parameters. 6. Nevi appearance (assessed by a dermatologist or other qualified site staff). Any nevi undergoing change of clinical concern during active treatment will be biopsied for follow up and evaluated by the central pathology lab. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
SAE & Clinical lab - at visit 1-8 Physical examination & Vital signs - at visit 1,2,3,5, 7, 8 & 9 and also at increasing dose V1 (unscheduled visit). ECG - visit 1 & 8 and also at increasing dose V1 (unscheduled visit). Nevi appearance - at visit 1,2,3,5,7,8 & 9 and also at increasing dose V1 (unscheduled visit). |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Long term extension study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Japan |
United Kingdom |
United States |
Germany |
Italy |
Norway |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |