OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)

Prior treatment

• Regular use of steroid, non-steroidal anti-inflammatory drug (NSAID), or colchicine within 30 days before screening
• Use of fish oil / omega-3 fatty acid supplements within two weeks before screening
• Positive drug and alcohol screen (including opiates, methadone, cocaine, amphetamines \[including ecstasy\], cannabinoids, barbiturates, benzodiazepines)
• Receiving any investigational therapy or any approved therapy for investigational use within 30 days or 5 half-lives prior to screening (whichever is longer)
• Received any vaccines (including the booster vaccination for COVID-19) within two weeks prior to Visit 1
• 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
• Subjects who have previously been exposed to OMT-28, whether responder or non-responder.
• Any use of statins (HMG-CoA reductase inhibitors)
• Use of quinine, tacrolimus, mycophenolate mofetil, ciclosporin, serotine receptor-type 1 agonist, penicillin G, penicillamine (d-penicillamine), nicotinic acid (niacin), colchicine, isotretinoin, and amiodarone, peroxisome proliferator-activated receptor (PPAR) activators, AMP-activated protein kinase (AMPK) activators, sirtuin activators, steroids, cyclooxygenase inhibitors.

Other illness

• 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
• Subjects with a history of cancer in the last 5 years
• Hypertension defined as systolic BP \>160 mmHg or diastolic BP \>100 mmHg at screening
• Uncontrolled Diabetes mellitus according to investigator's assessment
• Stroke-like episodes or seizures occurred within last 6 months
• Motoric abnormalities other than related to the mitochondrial disease interfering with the outcome parameters
• History or evidence of active tuberculosis (TB) infection, any co-disease with inflammatory condition (e.g., Inflammatory Bowel Disease (IBD) etc.)
• Patients with a positive hepatitis panel and/or positive immunodeficiency virus test at screening
• Any significant hepatic disease

Other

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• Chronic use of Metformin
• Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion
• 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

• Documented mutation resulting in mitochondrial disease: mitochondrial tRNA point mutations, including m3243A\>G, m8344A\>G, and single mtDNA deletions
• 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\[8\])
• GDF-15 between 1,200 ng/L and 10,000 ng/L at screening
• 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).