NCT06754098

Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency

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.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Cristina Domínguez González · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this clinical trial is to evaluate the efficacy and safety of Doxecitin and Doxribtimine (dC+dT) in adult participants with thymidine kinase 2 (TK2) deficiency attended in the Neuromuscular Unit of '12 de Octubre' Hospital. The main questions it aims to answer are: * Is dT+dC effective in the treatment of the adult participants with TK2 deficiency? * Is dT+dC safe in the treatment of adult participants with TK2 deficiency? Researchers will evaluate the effectiveness of the treatment doxecitin and doxribthymine in adult participants with TK2 deficiency. In addition, the mitochondrial DNA levels before and after treatment (extracted from the muscle and from uroepithelial cells) of these participants will be also studied.

Detailed description

This is an Open Label, single-arm, single-center clinical study to evaluate the efficacy and safety of dT+dC in adults with TK2 deficiency (TK2d). TK2 deficiency is one of several mitochondrial autosomal recessive disorders that are collectively referred to as mitochondrial DNA depletion and multiple deletions syndromes (MDDS), in fact, TK2d is an ultra-rare disease, presenting as progressive proximal muscle weakness in all patients; however, clinical presentations are heterogeneous in nature and manifest with variable levels of severity and functional impairment across patients. The study seeks to enroll patients under follow-up in the Neuromuscular Unit of '12 de Octubre' Hospital. All participants will be required to attend a screening visit at which their eligibility for the study will be determined. After signing the informed consent and verifying that they met all inclusion and exclusion criteria, participants will receive a daily dose of dT+dC in 3 equal divided doses administered orally at an approximate interval of 6 (±2) hours. dT+dC is to be initially dosed (commencing on Day 1) at 130 mg/kg/day of each nucleoside (130 mg/kg/day dC and 130 mg/kg/day dT), divided into 3 equal daily doses of approximately 43 mg/kg/dose. If the tolerability profile is acceptable after 2 weeks (approximately Day 15), the dose is to be increased to 260 mg/kg/day of each nucleoside (approximately 86 mg/kg/dose three-times daily, (TID). If the tolerability profile remains acceptable after an additional 2 weeks of dosing (approximately Day 29) the dose is to be further increased to 400 mg/kg/day (approximately 133 mg/kg/dose TID). The maximum dose is 400 mg/kg/day. The tolerability profile of the treatment will be evaluated based on whether the patient has diarrhea. The total number of participants for the safety and efficacy analysis will be 10 to 15 participants with progressive myopathy with respiratory involvement. The estimated duration of the study for individual participants will be 24 months. Although, based on previous experience in treating these patients, the investigators expect to see results within the first 6 to 12 months of treatment. It is hypothesized that dT+dC oral administration is safe, well tolerated and clinically beneficial in adults with TK2 deficiency.

Conditions

• Thymidine Kinase 2 (TK2 ) Deficiency
• Mitochondrial Myopathies

Interventions

Type	Name	Description
DRUG	Doxecitine and Doxribtimine	A combination of doxecitine and doxribtimine is administered orally in 3 equal doses given approximately 6 to 8 hours apart .Dose will be increased if the tolerability profile is good.

Timeline

• Start date: 2025-01-01
• Primary completion: 2027-01-31
• Completion: 2027-12-31
• First posted: 2024-12-31
• Last updated: 2025-07-28

Locations

1 site across 1 country: Spain