Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorCristina Domínguez González
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Signed informed consent by the subject.
Subject must be greater than 18 years of age at time of consent.
Genetic diagnosis of TK2 deficiency
North Star Ambulatory Assessment Scale (NSAA) less than 30
Disqualifiers
History of liver disease, or liver function test results (alanine aminotransferase [ALT], aspartate transaminase [AST], or total bilirubin) greater than or equal2 times (2X) the upper limit of normal. Patients with transaminases greater than 2 times (2X) can participate with the approval and monitoring of a doctor specializing in liver toxicity.
Participation in a previous trial of any investigational agent for primary mitochondrial disease within 1 year prior to informed consent, or use of any other investigational therapy within 30 days (or 3 half-lives, whichever is longer) prior to informed consent, or participation in other clinical studies, within 30 days prior to informed consent, which in the opinion of the study Sponsor, may potentially confound results from this study.
Pregnant (females 10.0 years old or older will have a pregnancy test at screening), or breastfeeding
Trial design
Design model
Single group
Treatments tested in this trial
Doxecitine and Doxribtimine
DrugA 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.
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: doxecitin and doxribthymine (dT+dC)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Efficacy - Motor Function Assessments: Neurological Exam using Medical Research Council (MRC Scale) Scale for Muscle Strength
Motor Function will be measured using the MRC scale. The scale provides a measure of Muscle Strength across a range from 0 (No visible muscle contraction) to 5 (Full strength)
Time frame
Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 242
Efficacy - Motor Function Assessments: 6-minute walk test
Motor Function will be measured using the 6-minute walk test (6MWT). Distance walked in meters over 6 minutes will be measured
Time frame
Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 243
Efficacy - Motor Function Assessments: North Star Ambulatory Assessment (NSAA)
Motor function will be assessed using the NSAA scale. The NSAA is a 17-item scale that grades performance of various functional activities on a scale graded 0 (unable to complete the activity), 1 (completes the activity independently but with modifications), and 2 (completes the activity without modifications)
Time frame
Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 244
Efficacy - Motor Function Assessments: 100 meter-time velocity test
Time to run 100 meters measured in seconds (sec)
Time frame
Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24Secondary outcomes
1
Safety as adverse events (AEs)
Number of participants who experience adverse events (AEs)
Time frame
Up to 24 months2
Safety as serious adverse events (SAEs)adverse events
Number of participants who experience serious adverse events (SAEs)
Time frame
Up to 24 monthsOther outcomes
1
Changes in the mtDNA levels before and after treatment
To assess change in mitochondrial DNA (mtDNA) levels, a muscle biopsy with a needle will be performed before entering the study and 6 months after the start of treatment
Time frame
6 month2
Changes in the peak oxygen consumption (VO2 max) test
A progressive exercise test will be undertaken at screening to assess peak oxygen consumption (VO2 max) using an electronically braked recumbent cycle ergometer.
Time frame
6 monthSponsors and contacts
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Cristina Domínguez González
Lead sponsor
Hospital Universitario 12 de Octubre
Sponsor institution
UCB Pharma
Collaborator
Source ClinicalTrials.gov