Folinic acid therapy in patients with Kearns-Sayre syndrome (KSS) and cerebral folate deficiency - mitoFolat

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsmedizin Goettingen

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Mar 2025 → ongoing

Decision date (initial)

2023-10-25

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Deutsche Forschungsgemeinschaft (DFG)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess the efficacy of folinic acid administration in comparison to no treatment to the clinical outcome with regard to KSS

Secondary objectives 5

1. To assess the efficacy of folinic acid administration compared to no treatment on change of 5MTHF concentrations in CSF
2. To assess the efficacy of folinic acid administration compared to no treatment on changes in brain volume
3. To assess the efficacy of folinic acid administration compared to no treatment on white matter alterations
4. To assess the efficacy of folinic acid administration compared to no treatment on changes in concentration in cholin and myo-inositol
5. To assess the efficacy of folinic acid administration compared to no treatment on correlation of folinic acid administration, 5MTHF and clinical outcome

Conditions and MedDRA coding

Kearns-Sayre-Syndrom

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Children and adolescents with KSS 6 to17 years of age
2. Disease onset at < 12 years of age
3. 5MTHF concentration < 20 nmol/L in CSF at screening. Result not older than 6 months
4. Diagnosed with a symptom complex consisting of progressive external ophthalmoplegia, ptosis, and pigmentary retinopathy, plus additionally one of: cardiac conduction defects, cerebellar syndrome or elevated CSF protein (>100mg/dl)
5. Identification of a single large-scale mtDNA deletion and/or duplication or mtDNA m.3243A>G mutation (rs199474667) in at least 2 different cell types (blood cells, urine cells)
6. Written informed consent of the legally designated representatives as of the minor who is capable to comprehend the nature, significance and implications of the clinical trial and to form a rational intention in the light of these facts
7. Willingness to use contraception to avoid pregnancy during trial

Exclusion criteria 12

1. Current and previous folic and folinic acid therapy (within the last 6 months before begin of the trial)
2. Consumption of synthetic folic or folinic acid (within the last 6 months before begin of the trial)
3. Acute infections (e.g. pneumonia, sepsis)
4. Contraindications for MRI/MRS (e.g. cochlear implant, pacemaker, etc.)
5. Pernicious anemia
6. Current medication with one or more of the following: phenobarbital, phenytoin, primidone, succinimides
7. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
8. Hypersensitivity to the active substance of the IMP or any other ingredient
9. Participation in any other interventional clinical trial within the last 30 days or 5 half-lifes of the investigational product of the other clinical trial, whichever is loinger, before the start of this trial
10. Pregnancy and/or breastfeeding.
11. Subjects dependent on sponsor, investigator or trial sites
12. Persons deprived of liberty or placed in an institution by judicial or administrative order

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. International Pediatric Mitochondrial Disease Scale (IPMDS) will be measured at 7 time points (baseline, months 3, 6, 9, 12, 15, and 18). Primary endpoint is the baseline adjusted mean difference between experimental treatment and no-treatment control group after 6 months. Changes between baseline value and the measurements after treatment start at month 6, 12, 18, respectively will also be analysed

Secondary endpoints 4

1. Biomarker (5-methyltetrahydrofolate, 5MTHF) concentration in CSF
2. Regional brain volume, size and extension of white matter alterations and myelination assessed by magnetic resonance imaging (MRI)
3. Concentrations of choline, myo-inositol assessed by 1H magnetic resonance spectroscopy (MRS)
4. Baseline adjusted mean differences between Newcastle Paediatric Mitochondrial Disease Scale (NPMDS)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsmedizin Goettingen

Sponsor organisation

Universitaetsmedizin Goettingen

Address

Robert-Koch-Strasse 40, Weende Weende

City

Goettingen

Postcode

37075

Country

Germany

Scientific contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Clinical Trials Unit UMG

Public contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Clinical Trials Unit UMG

Locations

1 EU/EEA country · 6 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

Documents 17 files

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

Application history

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