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

Primary Purpose

Primary Mitochondrial Disease

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
OMT-28
Sponsored by
Omeicos Therapeutics GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Mitochondrial Disease focused on measuring Myopathy, Cardiomyopathy, Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, Myoclonic epilepsy with ragged red fibers (MERRF), Maternally inherited diabetes and deafness (MIDD) syndrome, GDF-15

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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). Exclusion Criteria: Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study 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 Regular use of steroid, non-steroidal anti-inflammatory drug (NSAID), or colchicine within 30 days before screening Chronic use of Metformin Use of fish oil / omega-3 fatty acid supplements within two weeks before screening Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion Positive drug and alcohol screen (including opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines) Any significant hepatic disease 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 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 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.

Sites / Locations

  • Universitätsklinikum Bonn, Sektion Neuromuskuläre Erkrankungen, Klinik und Poliklinik für Neurologie, Venusberg-Campus 1, Gebäude 80, NPPRecruiting
  • Medizinisch Fakultät der Martin-Luther-Universität Halle-Wittenberg Universitätsklinik und Poliklinik für Neurologie Universitätsklinikum , Ernst-Grube-Str. 40Recruiting
  • Friedrich-Baur-Institut an der Neurologischen Klinik und Poliklinik, Klinikum der Universität München, Ludwig-Maximilians-Universität (LMU Klinikum), Ziemssenstr. 1aRecruiting
  • IRCCS Institute of Neurological Science of Bologna, University of Bologna, Department of Biomedical and Neuromotor Science (DIBINEM), Ospedale Bellaria Via Altura, 3Recruiting
  • U.O.C. di Neurologia e Malattie Neuromuscolari
  • IRCCS Istituto Neurologico Carlo Besta, SC Servizio Di Medicina Di Laboratorio - Genetica Medica E Neurogenetica, Via Celoria 11Recruiting
  • Azienda Ospedaliero Universitaria Pisana, P.O. Santa Chiara, U.O. Neurologia, Edificio 13, Via Roma 67Recruiting
  • UOC di neurofisiopatologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment with OMT-28

Arm Description

24mg OMT-28, oral capsule, for 12 weeks

Outcomes

Primary Outcome Measures

Responder rate
Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20% decrease
Number of Treatment Emergent Adverse Events (TEAE)
Compare the number of TEAEs during and between evaluation phases

Secondary Outcome Measures

Responder rate
Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20%
Change in plasma concentration of GDF-15 [ng/L]
GDF-15 plasma concentration during evaluation phases, change in GDF-15 concentration during evaluations phases and comparison of GDF-15 concentration between evaluation phases
Pharmacokinetics: Ctrough [ng/ml]
Trough plasma concentrations (Ctrough) of OMT-28
Pharmacokinetics: Cmax [ng/ml]
Plasma concentration of OMT-28 approximately at Cmax and one further timepoint after single dose

Full Information

First Posted
June 27, 2023
Last Updated
October 17, 2023
Sponsor
Omeicos Therapeutics GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT05972954
Brief Title
OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
Acronym
PMD-OPTION
Official Title
A Phase 2a Safety, Tolerability, and Pharmacodynamic Study of OMT-28 in PMD Patients With Myopathy and/or Cardiomyopathy and Inflammation (PMD-OPTION)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 22, 2023 (Actual)
Primary Completion Date
March 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Omeicos Therapeutics GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this clinical trial is to learn about the treatment effects of the investigational new drug OMT-28 in patients with Primary Mitochondrial Disease. The main question[s] it aims to answer are: Is OMT-28 safe and well tolerated in this patient population? Does OMT-28 reduce Growth Differentiation Factor 15 (GDF-15) and other relevant blood markers of mitochondrial dysfunction and inflammation? Does OMT-28 improve symptoms of the disease, e.g. fatigue or exercise intolerance? Participants will be asked to participate in 6 study visits at an experienced clinical center, including physical examinations and exercise tests, and take the study medication regularly once per day according to the protocol. Researchers will compare for every participant the results after 3 months and 6 months of treatment with a preceding 3 month period of standard care treatment to investigate the effects of OMT-28 on clinical parameters and a number of blood parameters.
Detailed Description
This is an open label, single-arm, multiple-phase and multicenter Phase 2a study to evaluate the efficacy, safety, and pharmacokinetics of a single OMT-28 dose (24 mg given once daily) in patients with Primary Mitochondrial Disease and clinical manifestation of myopathy and/or cardiomyopathy. Patients are eligible if they have Primary Mitochondrial Disease with a documented mitochondrial transfer ribonucleic acid (tRNA) point mutation, including m3243A>G, m8344A>G, or single mitochondrial DNA (mtDNA) deletions, a clinically relevant myopathy and/or cardiomyopathy confirmed following standard guidelines, a blood plasma GDF-15 concentration > 1200 ng/L and < 10.000 ng/L at screening Participation in the study is divided into 3 parts: Screening and baseline: 12 weeks Treatment: 24 weeks Safety follow-up: 4 weeks Total duration: 40 weeks Safety will be monitored throughout the study. Blood samples for safety, pharmacodynamics and pharmacokinetics will be collected at every of the 6 study visits. Exercise tests (6/12-minutes walking test, 5xSST), transthoracic echocardiography, patient reported outcomes (e.g. Fatigue Severity Scale and Patients' Global Impression of Change (PGIC) scale) will be assessed at prespecified visits. Patients will be provided with a diary to record timing of drug administration and clinical symptoms while not on site. Diaries will be reviewed and checked for compliance at each non-resident visit to the clinical site.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Mitochondrial Disease
Keywords
Myopathy, Cardiomyopathy, Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, Myoclonic epilepsy with ragged red fibers (MERRF), Maternally inherited diabetes and deafness (MIDD) syndrome, GDF-15

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment with OMT-28
Arm Type
Experimental
Arm Description
24mg OMT-28, oral capsule, for 12 weeks
Intervention Type
Drug
Intervention Name(s)
OMT-28
Intervention Description
once daily
Primary Outcome Measure Information:
Title
Responder rate
Description
Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20% decrease
Time Frame
12 weeks treatment vs. 12 weeks baseline
Title
Number of Treatment Emergent Adverse Events (TEAE)
Description
Compare the number of TEAEs during and between evaluation phases
Time Frame
up to 28 weeks
Secondary Outcome Measure Information:
Title
Responder rate
Description
Number of patients (responder rate) with a between phase difference in GDF-15 of at least 20%
Time Frame
24 weeks treatment vs. 12 weeks baseline
Title
Change in plasma concentration of GDF-15 [ng/L]
Description
GDF-15 plasma concentration during evaluation phases, change in GDF-15 concentration during evaluations phases and comparison of GDF-15 concentration between evaluation phases
Time Frame
12 weeks treatment vs. 12 weeks baseline
Title
Pharmacokinetics: Ctrough [ng/ml]
Description
Trough plasma concentrations (Ctrough) of OMT-28
Time Frame
weeks 12, 16, 24 and 28
Title
Pharmacokinetics: Cmax [ng/ml]
Description
Plasma concentration of OMT-28 approximately at Cmax and one further timepoint after single dose
Time Frame
week 12 and week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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). Exclusion Criteria: Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study 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 Regular use of steroid, non-steroidal anti-inflammatory drug (NSAID), or colchicine within 30 days before screening Chronic use of Metformin Use of fish oil / omega-3 fatty acid supplements within two weeks before screening Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion Positive drug and alcohol screen (including opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines) Any significant hepatic disease 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 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Manager
Phone
+49-30-9489-4810
Email
clinicalstudy@omeicos.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Fischer, MD
Organizational Affiliation
Omeicos Therapeutics GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Universitätsklinikum Bonn, Sektion Neuromuskuläre Erkrankungen, Klinik und Poliklinik für Neurologie, Venusberg-Campus 1, Gebäude 80, NPP
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cornelia Kornblum, Prof. Dr.
Facility Name
Medizinisch Fakultät der Martin-Luther-Universität Halle-Wittenberg Universitätsklinik und Poliklinik für Neurologie Universitätsklinikum , Ernst-Grube-Str. 40
City
Halle
ZIP/Postal Code
06120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Mensch, Dr.
Facility Name
Friedrich-Baur-Institut an der Neurologischen Klinik und Poliklinik, Klinikum der Universität München, Ludwig-Maximilians-Universität (LMU Klinikum), Ziemssenstr. 1a
City
Munich
ZIP/Postal Code
80336
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Klopstock, Prof. Dr.
Facility Name
IRCCS Institute of Neurological Science of Bologna, University of Bologna, Department of Biomedical and Neuromotor Science (DIBINEM), Ospedale Bellaria Via Altura, 3
City
Bologna
ZIP/Postal Code
40139
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valerio Carelli, Prof. Dr.
Facility Name
U.O.C. di Neurologia e Malattie Neuromuscolari
City
Messina
ZIP/Postal Code
98125
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olimpia Musumeci, Dr.
Facility Name
IRCCS Istituto Neurologico Carlo Besta, SC Servizio Di Medicina Di Laboratorio - Genetica Medica E Neurogenetica, Via Celoria 11
City
Milano
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Costanza Lamperti, Dr.
Facility Name
Azienda Ospedaliero Universitaria Pisana, P.O. Santa Chiara, U.O. Neurologia, Edificio 13, Via Roma 67
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelangelo Mancuso, Prof. Dr.
Facility Name
UOC di neurofisiopatologia
City
Roma
ZIP/Postal Code
8-00168
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Serenella Servidei, Prof. Dr.

12. IPD Sharing Statement

Learn more about this trial

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

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