Clinical trial NCT03845712: An Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With TK2 Deficiency
Official title: A Phase 2 Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With Thymidine Kinase 2 Deficiency (TK2)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2019-02-19
Enrollment: 47
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent by the parent(s) or legally authorized representative (LAR) and/or assent by the study participant (when applicable).
2. Confirmed genetic mutation in the TK2 gene.
3. Absence of other genetic disease or polygenic disease.
4. 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.
5. 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.
6. 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.
7. Willingness to maintain current treatment regimen and current exercise regimen for the duration of the clinical study.
8. 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 (ALT, AST, or total bilirubin) ≥2× upper limit of normal without prior Sponsor approval.
2. Other significant medical condition that, in the opinion of the Investigator or Study Sponsor, may confound interpretation of the clinical course of TK2 deficiency.

Primary outcomes:
measure: Safety as adverse events (AEs): number of participants who experience adverse events
timeFrame: Approximately 3 years
measure: Safety as determined by laboratory measurements
timeFrame: Approximately 3 years
measure: Safety as determined by electrocardiograms (ECGs)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Efficacy - Motor Function Assessments
timeFrame: Approximately 3 years
measure: Efficacy - Respiratory Status
timeFrame: Approximately 3 years
measure: Efficacy - Growth/Nutrition
timeFrame: Approximately 3 years
measure: Efficacy - Growth/Nutrition
timeFrame: Approximately 3 years
measure: Maximum plasma concentration (Cmax) of deoxycytidine and deoxythymidine
timeFrame: Approximately 3 years
measure: Time to maximum plasma concentration (Tmax) of deoxycytidine and deoxythymidine
timeFrame: Approximately 3 years
measure: AUC - area under the plasma concentration time curve of deoxycytidine and deoxythymidine
timeFrame: Approximately 3 years
measure: Apparent elimination half-life (t1/2) of deoxycytidine and deoxythymidine
timeFrame: Approximately 3 years
measure: Biomarkers (plasma from blood)
timeFrame: Approximately 3 years
measure: Biomarkers (plasma from blood)
timeFrame: Approximately 3 years
measure: Quality of life through patient questionnaire - Individualized Neuromuscular Quality of Life (INQoL)
timeFrame: Approximately 3 years
measure: Characterization of health care utilization
timeFrame: Approximately 3 years
measure: Efficacy Assessment: Clinical Global Impression of Improvement (CGI-I) and Patient Global Impression of Improvement (PGI-I)
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Tk0102 1005
state: New York
city: Haifa
country: Israel
facility: Tk0102 4038
city: Holon
country: Israel
facility: Tk0102 4039
city: Nehariya
country: Israel
facility: Tk0102 4037
city: Barcelona
country: Spain
facility: Tk0102 3102
city: Esplugues de Llobregat
country: Spain
facility: Tk0102 3121
city: Madrid
country: Spain
facility: Tk0102 3031
city: Sevilla
country: Spain
facility: Tk0102 3101
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: 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.