MABs Therapy m.3243A>G Mutation Carriers

NCT05063721 | Completed Phase 1 DMC

• 1 other identifier: NL68732.000.19
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Mitochondrial disorders are progressive, often fatal multisystem disorders, in 20-25% of the cases caused by heteroplasmic mutations in the mitochondrial DNA (mtDNA). At this moment, there is no effective treatment known to influence the disease process or manifestation. Myogenic stem cell-based therapies complementing defective muscle cells and fibres, are highly promising to combat the myopathy and exercise intolerance which affect \>50% of heteroplasmic mtDNA mutation carriers. Myogenic stem cells called mesoangioblasts (MABs), are currently the only myogenic precursors that fulfil all criteria to be used as advanced therapy medicinal product (ATMP) for systemic treatment. The researchers have demonstrated that MABs of most m.3243A\>G carriers contain no or only a low amount (\<10%) of the mtDNA mutation, allowing direct ex vivo expansion of patient-derived MABs. The overall aim is to induce muscle regeneration using these autologous MABs with a mutation load of \<10%, as an advanced therapy medicinal product (ATMP). Objective: The phase I trial will consist of an intra-arterial injection (via catheter in femoral artery) of the autologous MABs in the left lower leg of 5 m.3243A\>G patients.

Conditions

Mitochondrial Myopathies

Keywords

m.3243A>G; mesoangioblasts

Outcome Measures

Primary Outcomes (6)

• Assess blood flow in lower leg following intra-arterial delivery of autologous MABs as ATMP.

  Assess blood flow in lower leg using digital subtraction angiography (DSA).

  Day 1, directly after ATMP administration

• Assess adverse events following intra-arterial delivery of autologous MABs as ATMP in one lower leg.

  Assessment of adverse events

  1 month

• Assess systemic inflammation following intra-arterial delivery of autologous MABs as ATMP in one lower leg.

  Analysis inflammation markers blood (IL6, TNFa, CK)

  Day 1

• Assess systemic inflammation following intra-arterial delivery of autologous MABs as ATMP in one lower leg.

  Analysis inflammation markers blood (IL6, TNFa, CK)

  Day 28

• Assess local inflammation following intra-arterial delivery of autologous MABs as ATMP in one lower leg.

  Analysis inflammation markers (IL6, TNFa, CK) in tibialis anterior muscle

  Day 1

• Assess local inflammation following intra-arterial delivery of autologous MABs as ATMP in one lower leg.

  Analysis inflammation markers (IL6, TNFa, CK) in tibialis anterior muscle

  Day 28

Secondary Outcomes (3)

• Assess preliminary effectiveness based on MABs homing to the tibialis anterior muscle

  Day 1

• Assess preliminary effectiveness based on MABs-induced myogenesis

  Day 28

• Assess preliminary effectiveness based on changes in mtDNA mutation load in newly formed muscle fibers

  Day 28

Study Arms (2)

Intra-arterial delivery of autologous MABs

EXPERIMENTAL

Autologous mesoangioblasts (MABs) will be intra-arterially delivered to lower leg of participant

Biological: autologous mesoangioblasts

No intervention

NO INTERVENTION

intra-subject control

Interventions

autologous mesoangioblasts BIOLOGICAL

intra-arterial administration of autologous mesoangioblasts in lower leg (50x10E6/kg)

Intra-arterial delivery of autologous MABs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age: 18+
• Sex: male/female
• Patients with the m.3243A\>G mutation

You may not qualify if:

• Use of anti-coagulants, anti-thrombotics and other medication influencing coagulation
• Have a weekly alcohol intake of ≥ 35 units (men) or ≥ 24 units (women)
• Current history of drug abuse
• Deficient immune system or autoimmune disease
• Significant concurrent illness
• Ongoing participation in other clinical trials
• Major surgery within 4 weeks of the visit
• Vaccination within 4 weeks of the visit
• Pregnant or lactating women
• Psychiatric or other disorders likely to impact on informed consent
• Patients unable and/or unwilling to comply with treatment and study instructions
• Any other factor that in the opinion of the investigator excludes the patient from the study
• A history of strokes
• Allergy for contrast fluid
• Peripheral signs of ischemia or vasculopathy

Sponsors & Collaborators

• Maastricht University: lead

Study Sites (1)

Maastricht University

Maastricht, Netherlands

Location

Related Publications (1)

• van Tienen F, Zelissen R, Timmer E, van Gisbergen M, Lindsey P, Quattrocelli M, Sampaolesi M, Mulder-den Hartog E, de Coo I, Smeets H. Healthy, mtDNA-mutation free mesoangioblasts from mtDNA patients qualify for autologous therapy. Stem Cell Res Ther. 2019 Dec 21;10(1):405. doi: 10.1186/s13287-019-1510-8.

  PMID: 31864395 BACKGROUND

MeSH Terms

Conditions

Mitochondrial Myopathies

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Karin Faber, Prof. PhD MD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: October 1, 2021
• Study Start: March 1, 2020
• Primary Completion: September 16, 2022
• Study Completion: December 1, 2022
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)