Treatment for adults with TK2 deficiency using Doxecitin and Doxribthymine

An Off-Label Single Arm Clinical Study to Evaluate the Efficacy and Safety of Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency.

This study is testing if a new treatment called Doxecitin and Doxribthymine can help adults with TK2 deficiency feel better and improve their condition.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital Universitario 12 de Octubre (Academic / other)
• Locations: 1 site (Madrid)
• Trial ID: NCT06754098 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of Doxecitin and Doxribthymine in adult participants diagnosed with thymidine kinase 2 (TK2) deficiency. It is an open-label, single-arm study conducted at the Neuromuscular Unit of '12 de Octubre' Hospital in Madrid. Participants will receive a daily oral dose of the treatment, starting at 130 mg/kg/day and potentially increasing to 260 mg/kg/day based on tolerability. The study will also assess mitochondrial DNA levels in muscle and uroepithelial cells before and after treatment.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years with a genetic diagnosis of TK2 deficiency and moderate to severe disease symptoms.

Not a fit: Patients with mild TK2 deficiency or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve muscle function and overall health in patients with TK2 deficiency.

How similar studies have performed: While TK2 deficiency is an ultra-rare condition, similar approaches in mitochondrial disorders have shown promise, but this specific combination treatment is novel.

Eligibility criteria

Inclusion Criteria:

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:

   1. North Star Ambulatory Assessment Scale (NSAA) less than 30
   2. 6-minute walking test less than 450 meters
   3. Force Vital Capacity in the sitting position less than 70 percent or a drop in the decubitus position greater than 10 percent or need for mechanical ventilation.
   4. 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 (that is, following menarche until at least 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 (that is, less than 1 percent 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:

1. History of liver disease, or liver function test results (alanine aminotransferase \[ALT\], aspartate transaminase \[AST\], or total bilirubin) greater than or equal2 times (2X) the upper limit of normal. Patients with transaminases greater than 2 times (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 or older will have a pregnancy test at screening), or breastfeeding

Where this trial is running

Madrid

• Hospital Universitario 12 de Octubre — Madrid, Spain (Recruiting)

Study contacts

• Principal investigator: Cristina D Domínguez González, Dra. — Hospital 12 de Octubre
• Study coordinator: Cristina Domínguez González, Dra.

Conditions Thymidine Kinase 2 Deficiency; Mitochondrial Myopathies; TK2 deficiency; Primary Mitochondrial Myopathy; Deoxycytidine; Deoxythymidine; Mitochondrial DNA depletion and multiple deletions syndromes