Assess effect and safety of intra-arterial autologous mesoangioblast administration to the upper arm of m.3243A>G mutation carriers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Maastricht

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Musculoskeletal Diseases [C05], Phenomena and Processes [G] - Genetic Phenomena [G05]

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Maastricht UMC

External identifiers

EU CT number

2024-515129-27-00

EudraCT number

2022-003359-33

ClinicalTrials.gov

NCT05962333

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Assess effect of three intra-arterial administrations of autologous MABs to the BB muscle on of m.3243A>G patients by assessing strength and fatigue in BB muscles of both arms before and after last MABs administration in left arm. Assess safety of the three ATMP administrations to the upper left arm by checking for SAEs, vascular obstructions and changes in neurological vital signs.

Secondary objectives 1

1. Assess muscle mass in both BB muscles before and after treatment of left BB muscle. Assess morphology, m.3243A>G mutation load and mitochondrial respiratory capacity in muscle biopsies of the left BB muscle before the first and after the last MABs administration in left arm.

Conditions and MedDRA coding

m.3243A>G mutation causing mitochondrial myopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Written informed consent, Age: 18-64, Sex: male/female, Patients with the hetroplasmic m.3243A>G mutation.

Exclusion criteria 1

1. Use of dabigatran, apixaban, edoxaban or rivaroxaban (DOACs) as anti-coagulants; 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 with intervention; 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 - A history of strokes with signs of extra-pyramidal or pyramidal syndrome - Allergy for contrast fluid - Peripheral signs of ischemia or vasculopathy; Any other factor that in the opinion of the investigator excludes the patient from the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Assessment of safety parameters (angiography, 8h post-procedure monitoring of neurological vital signs, (S)AE) and assessment of changes in muscle strength and muscle fatigue of treated and untreated biceps brachii muscle using Biodex dynamometer measurements at baseline and 4-6 weeks after the third ATMP administration.

Secondary endpoints 1

1. Assess muscle mass, morphology, m.3243A>G mutation load and mitochondrial respiratory capacity in muscle biopsies of treated BB muscle

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Maastricht

Sponsor organisation

Academisch Ziekenhuis Maastricht

Address

P Debyelaan 25

City

Maastricht

Postcode

6229 HX

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Maastricht

Contact name

Florence van Tienen

Public contact point

Organisation

Academisch Ziekenhuis Maastricht

Contact name

Dick Nagelhout

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 6 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