Thymidine Kinase 2 Deficiency
Conditions
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
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.
Interventions
Doxecitine and doxribtimine is administered orally in 3 equal doses given approximately 6 to 8 hours apart. Doxecitine and doxribtimine is administered with food.
Sponsors
UCB BIOSCIENCES, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | From first administration of study drug until end of safety follow-up (up to approximately 7 years) | 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. |
| Incidence of TEAEs leading to study drug withdrawal | From first administration of study drug until end of safety follow-up (up to approximately 7 years) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Improvement (CGI-I) Response score | Assessed at end of study (approximately 7 years) | The CGI-I rating scale permits a global evaluation by the clinician of the study participant's improvement over time after study drug has been initiated. Improvement in a study participant's condition is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. |
| 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 | Cmin = Minimum plasma concentration |
| Mean maximum plasma concentration (Cmax) of dC and dT at steady state | Plasma samples will be collected at Months 1, 3, and 6 | Cmax = Maximum plasma concentration |
| 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 | AUC0-24 = Area under the plasma concentration-time curve from 0 to 24 hours |
Countries
Israel, Spain, United States
Contacts
STUDY_DIRECTORUCB Cares
001 844 599 2273
Outcome results
None listed