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

NCT03845712 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: TK01022018-004277-27U1111-1304-04232023-510427-29
• Study Type: interventional
• Target: 47
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

Thymidine Kinase 2 Deficiency

Keywords

Thymidine Kinase 2 Deficiency; TK2d; mitochondrial disorder; mitochondrial disease; Mitochondria; deoxycytidine and deoxythymidine; doxecitine and doxribtimine; MT1621; primary mitochondrial myopathy; mitochondrial depletion syndrome; Muscle weakness; Muscle atrophy; Loss of mobility

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events (TEAEs)

  An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.

  From first administration of study drug until end of safety follow-up (up to approximately 7 years)

• Incidence of TEAEs leading to study drug withdrawal

  An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.

  From first administration of study drug until end of safety follow-up (up to approximately 7 years)

Secondary Outcomes (4)

• Clinical Global Impression of Improvement (CGI-I) Response score

  Assessed at end of study (approximately 7 years)

• Mean minimum plasma concentration (Cmin) of deoxycytidine (dC) and deoxythymidine (dT) at steady state

  Plasma samples will be collected at Months 1, 3, and 6

• Mean maximum plasma concentration (Cmax) of dC and dT at steady state

  Plasma samples will be collected at Months 1, 3, and 6

• Mean area under the plasma concentration - time curve from time 0 to 24 hours (AUC0-24) of dC and dT at steady state

  Plasma samples will be collected at Months 1, 3, and 6

Study Arms (1)

doxecitine and doxribtimine

EXPERIMENTAL

This is an open label study with all participants in a single arm. Study participants will take doxecitine and doxribtimine up to a maximum of 800 mg/kg/day (400 mg/kg/day doxecitine and 400 mg/kg/day doxiribtimine).

Drug: doxecitine and doxribtimine

Interventions

doxecitine and doxribtimine DRUG

Doxecitine and doxribtimine is administered orally in 3 equal doses given approximately 6 to 8 hours apart. Doxecitine and doxribtimine is administered with food.

Also known as: MT1621, GMP grade dC/dT (deoxycytidine and deoxythymidine)

doxecitine and doxribtimine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• UCB BIOSCIENCES, Inc.: lead

Study Sites (8)

Tk0102 1005

New York, New York, 10032, United States

Location

Tk0102 4038

Haifa, Israel

Location

Tk0102 4039

Holon, Israel

Location

Tk0102 4037

Nehariya, Israel

Location

Tk0102 3102

Barcelona, Spain

Location

Tk0102 3121

Esplugues de Llobregat, Spain

Location

Tk0102 3031

Madrid, Spain

Location

Tk0102 3101

Seville, Spain

Location

Related Publications (1)

• Hernandez-Voth A, Sayas Catalan J, Corral Blanco M, Castano Mendez A, Martin MA, De Fuenmayor Fernandez de la Hoz C, Villena Garrido V, Dominguez-Gonzalez C. Deoxynucleoside therapy for respiratory involvement in adult patients with thymidine kinase 2-deficient myopathy. BMJ Open Respir Res. 2020 Nov;7(1):e000774. doi: 10.1136/bmjresp-2020-000774.

  PMID: 33246973 DERIVED

MeSH Terms

Conditions

Mitochondrial Diseases; Muscle Weakness; Muscular Atrophy

Interventions

Deoxycytidine; Thymidine

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 19, 2019
• Study Start: July 5, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

IL (3); ES (4); US (1)