An Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With TK2 Deficiency

A Phase 2 Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With Thymidine Kinase 2 Deficiency (TK2)

This is a Phase 2 prospective open-label treatment study of the safety and efficacy of doxecitine and doxribtimine in study participants with thymidine kinase 2 (TK2) deficiency who participated in the retrospective study MT-1621-101 [NCT03701568] or who were receiving nucleos(t)ide treatment and were approved by the Sponsor.

Inclusion Criteria:

• Signed informed consent by the parent(s) or legally authorized representative (LAR) and/or assent by the study participant (when applicable).
• Confirmed genetic mutation in the TK2 gene.
• Absence of other genetic disease or polygenic disease.
• Current treatment with nucleos(t)ides for TK2 deficiency. Study participants who were not previously enrolled in MT-1621-101 [NCT03701568] will require Sponsor approval to ensure that collection of clinical and functional measurements prior to treatment are sufficient to serve as baseline assessments for purposes of evaluating safety and efficacy.
• Female study participants must not be breastfeeding, have a negative pregnancy test at screening (females ≥10 years old), and have no intention to become pregnant during the course of the study. Female study participants 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. 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. In certain countries (if permitted by law), women of childbearing potential may instead agree to abide by heterosexual sexual abstinence during the study and for 30 days after the end of the study.
• Male study participants with sexual partners should use condoms for the duration of the study and for 30 days after the last dose of study drug to prevent passing study drug to the partner in the ejaculate. Male participants should be advised not to donate sperm for 30 days after the last dose of study drug.
• Willingness to maintain current treatment regimen and current exercise regimen for the duration of the clinical study.
• Willingness to comply with the study protocol, including but not limited to, all study procedures, study visits, and study drug compliance.

Exclusion Criteria:

• History of liver disease, or liver function test results (ALT, AST, or total bilirubin) ≥2× upper limit of normal without prior Sponsor approval.
• Other significant medical condition that, in the opinion of the Investigator or Study Sponsor, may confound interpretation of the clinical course of TK2 deficiency.