Open-Label and Long-term Extension Study with Dersimelagon (MT-7117) in Subjects with EPP or XLP

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tanabe Pharma America Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

19 Apr 2022 → ongoing

Decision date (initial)

2025-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-514466-38-00

EudraCT number

2021-001831-17

ClinicalTrials.gov

NCT05005975

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety

To evaluate the long-term safety and tolerability of oral MT-7117

Conditions and MedDRA coding

Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002850-PIP02-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. A subject will be eligible for enrollment in the study if ALL of the following criteria apply:
2. Subjects provided written informed consent to participate. For adolescent subjects, both adolescent assent and legal representative's consent will be provided.
3. Male and female subjects with a confirmed diagnosis of EPP or XLP based on medical history, aged 12 years to 75 years, inclusive, at Screening of studies MT-7117-G01 or MT-7117-A-302 and who have completed: MT-7117-G01 (completed through Week 58 [Visit 12]) or MT-7117-A-302 (completed through Week 58 [Visit 10]) or MT-7117-A-301 (completed EOT - Week 104 or Week 130) according to protocol amendment 1 or 2.
4. Subjects have a body weight of ≥ xx kg. (Please refer to protocol for full details)
5. Subjects are willing and able to travel to the study sites for all scheduled visits.
6. 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).
7. 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.
8. 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 of the Protocol.

Exclusion criteria 22

1. A subject will NOT be eligible for this study if ANY of the following criteria apply:
2. History or presence of photodermatoses other than EPP or XLP.
3. Presence or history of any hepatobiliary disease at Screening, determined as clinically significant by the Investigator.
4. Subjects with AST, ALT, ALP ≥ 3.0 × upper limit of normal (ULN) or TB > 1.5 × ULN at Screening. The TB level of > 1.5 × ULN listed in this exclusion criteria may not be applicable to subjects with a documented medical history of Gilbert’s syndrome. Please consult with the Sponsor for eligibility of subjects with elevated levels due to Gilbert’s syndrome.
5. Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator.
6. History of melanoma.
7. 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.
8. 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.
9. Presence of clinically significant acute or chronic renal disease based upon the subject’s medical records including haemodialysis; an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 as calculated by the CKD-EPI/Creatinine Equation for Glomerular Filtration Rate creatinine equation (2009) for adults and by the Schwartz creatinine equation for adolescents (2009) (Section 16.2, Appendix 2). MDRD/ Modification of Diet in Renal Disease can be used for adults per local recommendations.
10. 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.
11. Female subjects who are pregnant, lactating, or intending to become pregnant during the study.
12. Treatment with phototherapy or afamelanotide within 3 months, before baseline (Visit 2 or Re-entry Visit 2).
13. 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 or Re-entry Visit 2).
14. Chronic treatment with opioids, ketamine, or medical formulations or derivatives of cannabis within 4 weeks before baseline (Visit 2). Note: This exclusion criterion may not be applicable to subjects at Re-entry Visits. Acute use of scheduled analgesics more than 3 months before baseline (Visit 2) is allowed.
15. 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.
16. Previous treatment with any investigational agent other than MT-7117 within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer).
17. History of any hypersensitivity to the active ingredient and/or excipients (lactose monohydrate, hydroxypropyl cellulose, carmellose calcium, magnesium stearate, hypromellose, titanium dioxide, talc, polyethylene glycol, iron oxide yellow, iron oxide red, and iron oxide black).
18. Subjects who are unable to swallow tablets or have diseases significantly affecting the gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
19. Subjects who are legally institutionalized, or subjects under judicial protection.
20. Subjects with an immediate family member (i.e. spouse, parent/legal guardian, sibling, or a child) who is a member of study site staff or a member of the Sponsor’s study team.
21. Use of the following drugs (including but not limited to) within 1 week of baseline (Visit 2 or Re-entry 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.
22. Please refer to the protocol for the full list of exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tanabe Pharma America Inc.

Sponsor organisation

Tanabe Pharma America Inc.

Address

525 Washington Boulevard Suite 1100

City

Jersey City

Postcode

07310-2604

Country

United States

Scientific contact point

Organisation

Tanabe Pharma America Inc.

Contact name

General Information, Tanabe Pharma Europe Ltd.

Public contact point

Organisation

Tanabe Pharma America Inc.

Contact name

General Information, Tanabe Pharma Europe Ltd.

Third parties 9

Locations

10 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 91 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications