A Phase 2a Safety, Tolerability, and Pharmacodynamic Study of OMT-28 in PMD patients with myopathy and/or cardiomyopathy and inflammation (PMD-OPTION)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

OMEICOS Therapeutics GmbH

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

22 May 2023 → 14 May 2025

Decision date (initial)

2023-12-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-508541-41-00

EudraCT number

2022-003307-16

ClinicalTrials.gov

NCT05972954

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Safety

- To determine the responder rate of patients with a between phase difference in GDF-15 of at least 20% decrease after 12 weeks of treatment.
- To assess safety and tolerability of OMT-28 at 24 mg

Conditions and MedDRA coding

Primary Mitochondrial Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Any gender, age 18 to 60 years
2. Documented mutation resulting in mitochondrial disease: mitochondrial tRNA point mutations, including m3243A>G, m8344A>G, and single mtDNA deletions
3. Diagnosis of Cardiomyopathy defined as LV hypertrophy and/or LVEF<50% and/or late gadolinium enhancement on cardiac MRI and/or Myopathy as defined by the International Workshop: Outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adult (Mancuso et al. 2017)
4. GDF-15 between 1,200 to 10,000 pg/mL measured at screening
5. Ability to perform the exercise tests
6. Willing and able to provide a signed Informed Consent, as well as written documentation in accordance with country and local privacy requirements, e.g., written data protection consent
7. Able and willing to comply with the requirements of this study protocol
8. Both female patients, as well as, female partners of male patients who are of child- bearing potential must be willing to not become pregnant for the complete duration of the study (30 days after the last dose of study medication).

Exclusion criteria 22

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
2. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
3. Subjects with a history of cancer in the last 5 years
4. Hypertension defined as systolic BP >160 mmHg or diastolic BP >100 mmHg at screening
5. Uncontrolled Diabetes mellitus according to investigator's assessment
6. Stroke-like episodes or seizures occurred within last 6 months
7. Motoric abnormalities other than related to the mitochondrial disease interfering with the outcome parameters
8. History or evidence of active tuberculosis (TB) infection, any co-disease with inflammatory condition (e.g. Inflammatory Bowel Disease (IBD) etc.)
9. Patients with a positive hepatitis panel and/or positive immunodeficiency virus test at screening
10. Regular use of steroid, non-steroidal anti-inflammatory drug (NSAID), or colchicine within 30 days before screening
11. Chronic use of Metformin
12. Use of fish oil / omega-3 fatty acid supplements within 2 weeks before screening
13. Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion
14. Positive drug and alcohol screen (including opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines)
15. Any significant hepatic disease (defined as the presence of at least one of the following: AST, ALT, GGT, total bilirubin, or alkaline phosphatase >3x upper limit normal)
16. Receiving any investigational therapy or any approved therapy for investigational use within 30 days or 5 half-lives prior to screening (whichever is longer)
17. Received any vaccines (including the booster vaccination for Covid- 19) within two weeks prior to Visit 1
18. Females of childbearing potential (those who are not surgically sterilized or post- menopausal for at least 1 year) are excluded from participation in the study unless they agree to use adequate contraception as described in Appendix 11.4 of the protocol
19. Males (including sterilized subjects) and whose female partners have child-bearing potential, must agree to use male contraception (condoms) during the period from the time of signing the informed consent form (ICF) through 30 days after the last dose of study drug. They must agree to immediately inform the investigator if his partner becomes pregnant during the study.
20. Subjects who have previously been exposed to OMT-28, whether responder or nonresponder
21. Any use of statins (HMG-CoA reductase inhibitors)
22. Use of quinine, tacrolimus, mycophenolate mofetil, ciclosporin, serotine receptortype 1 agonist, penicillin G, penicillamine (dpenicillamine), nicotinic acid (niacin), colchicine, isotretinoin, and amiodarone, PPAR activators, AMPK activators, Sirtuin activators, Steroids, COX-inhibitors

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary Efficacy Endpoint: Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20% decrease after 12 weeks of treatment.
2. Primary Safety Endpoints: Incidence, severity, seriousness, reported causality, and duration of TEAEs, clinically significant changes in safety laboratory, vital signs, and 12-lead ECG

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

OMEICOS Therapeutics GmbH

Sponsor organisation

OMEICOS Therapeutics GmbH

Address

Robert-Roessle-Strasse 10, Buch Buch

City

Berlin

Postcode

13125

Country

Germany

Scientific contact point

Organisation

OMEICOS Therapeutics GmbH

Contact name

Dr. Robert Fischer

Public contact point

Organisation

OMEICOS Therapeutics GmbH

Contact name

Dr. Robert Fischer

Third parties 8

Locations

3 EU/EEA countries · 9 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 files

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

Application history

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