Thymidine Kinase 2 (TK2 ) DeficiencyPhase 2NCT06754098
Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency
A Phase 2 study testing Doxecitine and Doxribtimine in people with Thymidine Kinase 2 (TK2 ) Deficiency and Mitochondrial Myopathies, run by Cristina Domínguez González at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thymidine Kinase 2 (TK2 ) Deficiency, Mitochondrial Myopathies
- What is being tested?
- Doxecitine and Doxribtimine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2025to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent by the subject.
- Subject must be greater than 18 years of age at time of consent.
- Genetic diagnosis of TK2 deficiency
- Subject should have evidence of a moderate to severe disease, with motor and or respiratory involvement, shown by one of the following:
- North Star Ambulatory Assessment Scale (NSAA) less than 30
- 6-minute walking test less than 450 meters
Show all 11Show fewer
- Force Vital Capacity in the sitting position less than 70 percent or a drop in the decubitus position greater than 10 percent or need for mechanical ventilation.
- Disabling symptoms and evidence of motor and/or respiratory function progressive decline.
- Female subjects must have no intention to become pregnant during the study. Female subjects who are of childbearing potential (that is, following menarche until at least 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, and be willing to have additional pregnancy tests conducted during the study. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (that is, less than 1 percent per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method.
- Male subjects with partners of childbearing potential must agree to use effective contraception methods during the study and for at least 90 days after the last dose of the study medication. Acceptable methods include the use of condoms combined with spermicidal foam/gel/film/cream/suppository.
- Willingness to comply with the study protocol, including but not limited to, all study procedures, study visits, and study drug compliance.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, Madrid, 28041
Cristina Domínguez González, Dra., +34 917792582, cdgonzalez@salud.madrid.org
About this study
Official title: 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.
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:
Read more
- 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.
Read the 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.
- Being tested
- Doxecitine and Doxribtimine
- Keywords
- TK2 deficiency, Primary Mitochondrial Myopathy, Deoxycytidine (dC), Deoxythymidine (dT), Mitochondrial DNA depletion and multiple deletions syndromes (MDDS)
- Medical subject headings
- Mitochondrial Myopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doxecitine and DoxribtimineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| doxecitin and doxribthymine (dT+dC) | 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). Receives: Drug: Doxecitine and Doxribtimine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
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
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
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)
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Efficacy - Motor Function Assessments: 100 meter-time velocity test
Time to run 100 meters measured in seconds (sec)
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Efficacy - Motor Function Assessments: Fatigue Scale test
Motor function will be assessed Fatigue Scale test. The FACIT-Fatigue is a 13-item patient-reported outcome measure (range from 0 to 52: 0 = very much fatigued, 52 = not at all fatigued) assessing fatigue over the previous week
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Efficacy - Respiratory Assessments measured by spirometry
- Sitting Forced Vital Capacity (Sitting FVC) measure in percentage (%)
- Drop in FVC lying down measured in percentage (%)
- Maximal Inspiratory Pressure (MIP) measure in percentage: Evaluation of the strength of respiratory muscles is performed with measurements of MIP expressed in percentage (%)
- Maximal Inspiratory Pressure (MEP) measure in percentage: Evaluation of the strength of respiratory muscles is performed with measurements of MEP expressed in percentage (%)
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Efficacy - Respiratory Assessments: Use of ventilatory support (Use and Type )
Use and Type of mechanical ventilation (MV) [bilevel positive airway pressure (BiPAP) and/or continuous positive airway pressure (CPAP)] per subject will be assessed
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Efficacy - Respiratory Assessments: Time of use of ventilatory support
Total of hours of use of mechanical ventilation (MV) per subject will be assessed
Measured: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Serum Biomarkers: lactate levels
Number of participants with normal vs abnormal lactate levels measured in mmol/l
Measured: Up to 24 months
Serum Biomarkers: Growth/differentiation factor-15 (GDF15 )
Number of participants with normal vs abnormal Growth/differentiation factor-15 (GDF15) levels measured in mmol/l compared to normal ranges
Measured: Up to 24 months
Secondary outcomes (2)
Safety as adverse events (AEs)
Number of participants who experience adverse events (AEs)
Measured: Up to 24 months
Safety as serious adverse events (SAEs)adverse events
Number of participants who experience serious adverse events (SAEs)
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2024
- Study start1 Jan 2025
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Thymidine Kinase 2 (TK2 ) DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study seeks to enroll 10 to 15 patients under follow-up in the Neuromuscular Unit of '12 de Octubre' Hospital. All subjects will be required to attend a screening visit at which their eligibility for the study will be determined.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cristina Domínguez González
- Sponsor type
- University, hospital or other
- Collaborators
- UCB Pharma
- Responsible party
- Sponsor-investigator, Cristina Domínguez González, Hospital Universitario 12 de Octubre
- Investigators
- Cristina D Domínguez González, Dra., Principal investigator, Hospital 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06754098
- Sponsor's protocol ID
- LOTK2D
- Other IDs
- 2024-510763-35-00
- Status last verified
- Feb 2026
- First submitted
- 23 Dec 2024
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dominguez-Gonzalez C, Badosa C, Madruga-Garrido M, Marti I, Paradas C, Ortez C, Diaz-Manera J, Berardo A, Alonso-Perez J, Trifunov S, Cuadras D, Kalko SG, Blazquez-Bermejo C, Camara Y, Marti R, Mavillard F, Martin MA, Montoya J, Ruiz-Pesini E, Villarroya J, Montero R, Villarroya F, Artuch R, Hirano M, Nascimento A, Jimenez-Mallebrera C. Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy. Sci Rep. 2020 Jun 22;10(1):10111. doi: 10.1038/s41598-020-66940-8.
PubMed 32572108Berardo A, Dominguez-Gonzalez C, Engelstad K, Hirano M. Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies. J Neuromuscul Dis. 2022;9(2):225-235. doi: 10.3233/JND-210786.
PubMed 35094997Bermejo-Guerrero L, Hernandez-Voth A, Serrano-Lorenzo P, Blazquez A, Martin-Jimenez P, Martin MA, Dominguez-Gonzalez C. Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report. Mitochondrion. 2024 May;76:101879. doi: 10.1016/j.mito.2024.101879. Epub 2024 Apr 9.
PubMed 38599303Dominguez-Gonzalez C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodriguez FJ, Donati MA, Kleinsteuber K, Marti I, Martin-Hernandez E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Alvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Marti R, Paradas C, Hirano M. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy. Ann Neurol. 2019 Aug;86(2):293-303. doi: 10.1002/ana.25506. Epub 2019 Jun 17.
PubMed 31125140
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT06754098
- Acronym / sponsor ID
- LOTK2D
- Keywords
- TK2 deficiency, Primary Mitochondrial Myopathy, Deoxycytidine (dC), Deoxythymidine (dT), Mitochondrial DNA depletion and multiple deletions syndromes (MDDS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Cristina Domínguez GonzálezUniversity, hospital or other
- Collaborators
- UCB Pharma
- Study start
- 1 Jan 2025 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 31 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study seeks to enroll 10 to 15 patients under follow-up in the Neuromuscular Unit of '12 de Octubre' Hospital. All subjects will be required to attend a screening visit at which their eligibility for the study will be determined.
| Arm | Type | Receives |
|---|---|---|
| doxecitin and doxribthymine (dT+dC) | Experimental | Drug: Doxecitine and DoxribtimineThis 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed informed consent by the subject.
- Subject must be greater than 18 years of age at time of consent.
- Genetic diagnosis of TK2 deficiency
- Subject should have evidence of a moderate to severe disease, with motor and or respiratory involvement, shown by one of the following:
- Female subjects must have no intention to become pregnant during the study. Female subjects who are of childbearing potential (that is, following menarche until at least 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, and be willing to have additional pregnancy tests conducted during the study. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (that is, less than 1 percent per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxecitine and DoxribtimineA 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. | Drug | doxecitin and doxribthymine (dT+dC) |
Primary outcome
Efficacy - Motor Function Assessments: Neurological Exam using Medical Research Council (MRC Scale) Scale for Muscle Strength
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
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)
Efficacy - Motor Function Assessments: 6-minute walk test
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Motor Function will be measured using the 6-minute walk test (6MWT). Distance walked in meters over 6 minutes will be measured
Efficacy - Motor Function Assessments: North Star Ambulatory Assessment (NSAA)
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
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)
Efficacy - Motor Function Assessments: 100 meter-time velocity test
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Time to run 100 meters measured in seconds (sec)
Efficacy - Motor Function Assessments: Fatigue Scale test
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Motor function will be assessed Fatigue Scale test. The FACIT-Fatigue is a 13-item patient-reported outcome measure (range from 0 to 52: 0 = very much fatigued, 52 = not at all fatigued) assessing fatigue over the previous week
Efficacy - Respiratory Assessments measured by spirometry
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
* Sitting Forced Vital Capacity (Sitting FVC) measure in percentage (%) * Drop in FVC lying down measured in percentage (%) * Maximal Inspiratory Pressure (MIP) measure in percentage: Evaluation of the strength of respiratory muscles is performed with measurements of MIP expressed in percentage (%) * Maximal Inspiratory Pressure (MEP) measure in percentage: Evaluation of the strength of respiratory muscles is performed with measurements of MEP expressed in percentage (%)
Efficacy - Respiratory Assessments: Use of ventilatory support (Use and Type )
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Use and Type of mechanical ventilation (MV) [bilevel positive airway pressure (BiPAP) and/or continuous positive airway pressure (CPAP)] per subject will be assessed
Efficacy - Respiratory Assessments: Time of use of ventilatory support
Time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24
Total of hours of use of mechanical ventilation (MV) per subject will be assessed
Serum Biomarkers: lactate levels
Time frame: Up to 24 months
Number of participants with normal vs abnormal lactate levels measured in mmol/l
Serum Biomarkers: Growth/differentiation factor-15 (GDF15 )
Time frame: Up to 24 months
Number of participants with normal vs abnormal Growth/differentiation factor-15 (GDF15) levels measured in mmol/l compared to normal ranges
2 secondary outcomes
Safety as adverse events (AEs)
Time frame: Up to 24 months
Safety as serious adverse events (SAEs)adverse events
Time frame: Up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Background: PubMed 32572108Dominguez-Gonzalez C, Badosa C, Madruga-Garrido M, Marti I, Paradas C, Ortez C, Diaz-Manera J, Berardo A, Alonso-Perez J, Trifunov S, Cuadras D, Kalko SG, Blazquez-Bermejo C, Camara Y, Marti R, Mavillard F, Martin MA, Montoya J, Ruiz-Pesini E, Villarroya J, Montero R, Villarroya F, Artuch R, Hirano M, Nascimento A, Jimenez-Mallebrera C. Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy. Sci Rep. 2020 Jun 22;10(1):10111. doi: 10.1038/s41598-020-66940-8.
- Background: PubMed 35094997Berardo A, Dominguez-Gonzalez C, Engelstad K, Hirano M. Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies. J Neuromuscul Dis. 2022;9(2):225-235. doi: 10.3233/JND-210786.
- Background: PubMed 38599303Bermejo-Guerrero L, Hernandez-Voth A, Serrano-Lorenzo P, Blazquez A, Martin-Jimenez P, Martin MA, Dominguez-Gonzalez C. Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report. Mitochondrion. 2024 May;76:101879. doi: 10.1016/j.mito.2024.101879. Epub 2024 Apr 9.
- Background: PubMed 31125140Dominguez-Gonzalez C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodriguez FJ, Donati MA, Kleinsteuber K, Marti I, Martin-Hernandez E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Alvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Marti R, Paradas C, Hirano M. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy. Ann Neurol. 2019 Aug;86(2):293-303. doi: 10.1002/ana.25506. Epub 2019 Jun 17.
- Individual participant dataSharing planned: No
Related trials for Thymidine Kinase 2 (TK2 ) Deficiency
Active, not recruitingPhase 1/2
Treatment of TK2 Deficiency With Thymidine and Deoxycytidine
Mitochondrial DNA Depletion Syndrome 2 Myopathic Type, Thymidine Kinase 2 Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cristina D Domínguez González, Dra. principal investigator
Hospital 12 de Octubre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Doxecitine and Doxribtimine in people with Thymidine Kinase 2 (TK2 ) Deficiency and Mitochondrial Myopathies, run by Cristina Domínguez González at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cristina Domínguez González, Dra. (+34 917792582, cdgonzalez@salud.madrid.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy - Motor Function Assessments: Neurological Exam using Medical Research Council (MRC Scale) Scale for Muscle Strength (time frame: Day 1, Months 1, 2, 3, 12, 15, 18, 21 and 24). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06754098, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.