An Off-Label Single Arm Clinical Study to Evaluate the Efficacy and Safety of doxecitine and doxribtimine in Adult Subjects with Thymidine Kinase 2 (TK2) Deficiency

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital Universitario 12 De Octubre

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Nervous System Diseases [C10]

Trial duration

5 Nov 2024 → ongoing

Decision date (initial)

2024-07-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Fundacion de investigación Biomedica del Hospital 12 de Octubre

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of dT+dC in adults with TK2d

Secondary objectives 1

1. To evaluate the safety of dT+dC in adults with TK2d.

Conditions and MedDRA coding

Organic compound

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed informed consent by the subject.
2. Subject must be greater than 18 years of age at time of consent.
3. Genetic diagnosis of TK2 deficiency
4. Subject should have evidence of a moderate to severe disease, with motor and or respiratory involvement, shown by one of the following: a. North Star Ambulatory Assessment Scale (NSAA) < 30 b. 6-minute walking test < 450 meters c. Force Vital Capacity in the sitting position < 70% or a drop in the decubitus position > 10% or need for mechanical ventilation. d. Disabling symptoms and evidence of motor and/or respiratory function progressive decline
5. Female subjects must have no intention to become pregnant during the study. Female subjects who are of childbearing potential (ie, following menarche until ≥1 year post-menopausal if not anatomically and physiologically incapable of becoming pregnant) must agree and commit to the use of highly effective methods of birth control for the duration of the study and for 30 days after the end of the study, and be willing to have additional pregnancy tests conducted during the study. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (ie, <1% per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method.
6. Male subjects with partners of childbearing potential must agree to use effective contraception methods during the study and for at least 90 days after the last dose of the study medication. Acceptable methods include the use of condoms combined with spermicidal foam/gel/film/cream/suppository
7. Willingness to comply with the study protocol, including but not limited to, all study procedures, study visits, and study drug compliance.

Exclusion criteria 3

1. History of liver disease, or liver function test results (alanine aminotransferase [ALT], aspartate transaminase [AST], or total bilirubin) ≥ 2X ~ upper limit of normal. Patients with transaminases > 2X can participate with the approval and monitoring of a doctor specializing in liver toxicity.
2. Participation in a previous trial of any investigational agent for primary mitochondrial disease within 1 year prior to informed consent, or use of any other investigational therapy within 30 days (or 3 half-lives, whichever is longer) prior to informed consent, or participation in other clinical studies, within 30 days prior to informed consent, which in the opinion of the study Sponsor, may potentially confound results from this study.
3. Pregnant (females ≥10.0 years old will have a pregnancy test at screening), or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the efficacy of dT+dC in adults with TK2d.

Secondary endpoints 1

1. To evaluate the safety of dT+dC in adults with TK2d.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital Universitario 12 De Octubre

Sponsor organisation

Hospital Universitario 12 De Octubre

Address

Bloque D, Avenida De Cordoba Sn Avenida De Cordoba Sn

City

Madrid

Postcode

28041

Country

Spain

Scientific contact point

Organisation

Hospital Universitario 12 De Octubre

Contact name

Cristina Domínguez González

Public contact point

Organisation

Hospital Universitario 12 De Octubre

Contact name

Cristina Domínguez González

Third parties 1

Locations

1 EU/EEA country · 1 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 6 files

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

Application history

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