Thymidine Kinase 2 DeficiencyPhase 3NCT04581733
A Study of the Efficacy and Safety of MT1621 in Thymidine Kinase 2 (TK2) Deficiency (Treatment naïve)
A Phase 3 study testing MT1621 in people with Thymidine Kinase 2 Deficiency, run by Zogenix MDS, Inc..
Trial summary
This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study of the efficacy and safety of MT1621 in pediatric and adolescent patients with thymidine kinase 2 deficiency (TK2d). Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Thymidine Kinase 2 Deficiency
- What is being tested?
- MT1621
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2022to 30 Apr 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subject must be aged birth to <18 years of age on the day of consent.
- Diagnosis of TK2 deficiency based on confirmed disease-causing mutation(s) in the TK2 gene.
- Onset of TK2d at ≤12 years of age as defined as the age at which the first TK2d symptom occurred.
Who cannot join
- Documented clinically significant central nervous system involvement.
- ALT or AST >3 x upper limit of normal and total bilirubin > 2 x ULN or International Normalized Ratio (INR) >1.5.
- EtCO2>45 mmHg if not on ventilatory support
- Current or prior treatment with nucleos(t)ides for TK2d.
About this study
Official title: A Phase 3b Single Arm Clinical Study to Evaluate the Efficacy and Safety of MT1621 in Nucleos(t)Ide Treatment Naïve Pediatric and Adolescent Subjects With Thymidine Kinase 2 (TK2) Deficiency
This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study of the efficacy and safety of MT1621 in pediatric and adolescent patients with thymidine kinase 2 deficiency (TK2d). In order to be eligible for this study, participants must have genetic confirmation of TK2d and must not have ever received MT1621 or nucleos(t)ides before entering the study.
Read the detailed description
Thymidine kinase 2 (TK2) is a protein involved in the normal function of mitochondria. Thymidine kinase 2 deficiency (TK2d) is a form of mitochondrial DNA depletion syndrome and is a very rare inherited genetic disorder. TK2d leads to abnormally low amounts of DNA in mitochondria and because of this defect, the mitochondria are not able to provide the energy that cells need to function properly, which causes severe muscle weakness, along with host of additional symptoms that may involve the respiration, feeding, and ambulation, and can progress until patients lose many of these abilities. There are no FDA-approved medicines to treat TK2d.
MT1621 is a therapy that targets the underlying pathophysiology of TK2d by restoring mitochondrial DNA (mtDNA) replication fidelity. MT1621 consists of a combination of deoxynucleosides (the building blocks of mtDNA) given orally. Deoxynucleoside combination therapy improves nucleotide balance, increases mtDNA copy number, improves cell function, and prolongs life in preclinical models of TK2d.
This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study to assess the efficacy and safety of MT1621 in treatment naïve pediatric and adolescent subjects <18 years of age with TK2d. The study seeks to enroll approximately 16 subjects globally in this ultra rare disease.
- Conditions
- Thymidine Kinase 2 Deficiency
- Being tested
- MT1621
- Keywords
- TK2, TK2d, mitochondrial disorder, mitochondrial disease, Mitochondria, deoxythymidine/deoxythymidine substrate enhancement therapy, dC/dT, deoxythymidine/deoxythymidine, primary mitochondrial myopathy, mitochondrial depletion syndrome, Muscle weakness, Muscle atrophy, Loss of mobility, Thymidine kinase 2 deficiency
- Medical subject headings
- Mitochondrial Diseases, Muscle Weakness, Muscular Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MT1621Drug
Also called Deoxycytidine (dC) and deoxythymidine (dT)
All patients will receive MT1621 up to a target dose of 400 mg/kg/day each dC and dT, as tolerated.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Male and female Participants <18 years Receives: Drug: MT1621 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects acquiring a Motor Milestone
Proportion of subjects acquiring a motor milestone not present at baseline after 12 months of MT1621 treatment.
Measured: 12 months
Secondary outcomes (2)
Time to Acquisition of a Motor Milestone
Time to Acquisition of a Motor Milestone that was not present at baseline after 12 months of treatment.
Measured: 12 months
Survival
Survival after 12 months of treatment
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start30 Sep 2022 (estimated)
- Primary completion31 Mar 2025 (estimated)
- Study completion30 Apr 2025 (estimated)
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thymidine Kinase 2 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a Phase 3b study. All participants will receive MT1621 up to a target dose of 400 mg/kg/day
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zogenix MDS, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- UCB Cares, Study director, 001 844 599 2273
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04581733
- Sponsor's protocol ID
- MT-1621-104
- Status last verified
- Aug 2023
- First submitted
- 29 Sep 2020
- Last updated
- 1 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b Single Arm Clinical Study to Evaluate the Efficacy and Safety of MT1621 in Nucleos(t)Ide Treatment Naïve Pediatric and Adolescent Subjects With Thymidine Kinase 2 (TK2) Deficiency
- ClinicalTrials.gov ID
- NCT04581733
- Acronym / sponsor ID
- MT-1621-104
- Conditions
- Thymidine Kinase 2 Deficiency
- Keywords
- TK2, TK2d, mitochondrial disorder, mitochondrial disease, Mitochondria, deoxythymidine/deoxythymidine substrate enhancement therapy, dC/dT, deoxythymidine/deoxythymidine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor Decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Zogenix MDS, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Sep 2022 (estimated)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 30 Apr 2025 (estimated)
- First posted
- 9 Oct 2020 (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.
This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study of the efficacy and safety of MT1621 in pediatric and adolescent patients with thymidine kinase 2 deficiency (TK2d). In order to be eligible for this study, participants must have genetic confirmation of TK2d and must not have ever received MT1621 or nucleos(t)ides before entering the study.
Detailed description
Thymidine kinase 2 (TK2) is a protein involved in the normal function of mitochondria. Thymidine kinase 2 deficiency (TK2d) is a form of mitochondrial DNA depletion syndrome and is a very rare inherited genetic disorder. TK2d leads to abnormally low amounts of DNA in mitochondria and because of this defect, the mitochondria are not able to provide the energy that cells need to function properly, which causes severe muscle weakness, along with host of additional symptoms that may involve the respiration, feeding, and ambulation, and can progress until patients lose many of these abilities. There are no FDA-approved medicines to treat TK2d.
MT1621 is a therapy that targets the underlying pathophysiology of TK2d by restoring mitochondrial DNA (mtDNA) replication fidelity. MT1621 consists of a combination of deoxynucleosides (the building blocks of mtDNA) given orally. Deoxynucleoside combination therapy improves nucleotide balance, increases mtDNA copy number, improves cell function, and prolongs life in preclinical models of TK2d.
This is a Phase 3b, prospective, single-arm, multicenter, open-label treatment study to assess the efficacy and safety of MT1621 in treatment naïve pediatric and adolescent subjects <18 years of age with TK2d. The study seeks to enroll approximately 16 subjects globally in this ultra rare disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a Phase 3b study. All participants will receive MT1621 up to a target dose of 400 mg/kg/day
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: MT1621Male and female Participants <18 years |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Subject must be aged birth to <18 years of age on the day of consent.
- Diagnosis of TK2 deficiency based on confirmed disease-causing mutation(s) in the TK2 gene.
- Onset of TK2d at ≤12 years of age as defined as the age at which the first TK2d symptom occurred.
Key exclusion criteria (4 listed)
- Documented clinically significant central nervous system involvement.
- ALT or AST >3 x upper limit of normal and total bilirubin > 2 x ULN or International Normalized Ratio (INR) >1.5.
- EtCO2>45 mmHg if not on ventilatory support
- Current or prior treatment with nucleos(t)ides for TK2d.
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 |
|---|---|---|
| MT1621Also: Deoxycytidine (dC) and deoxythymidine (dT)All patients will receive MT1621 up to a target dose of 400 mg/kg/day each dC and dT, as tolerated. | Drug | Single Arm |
Primary outcome
Proportion of subjects acquiring a Motor Milestone
Time frame: 12 months
Proportion of subjects acquiring a motor milestone not present at baseline after 12 months of MT1621 treatment.
2 secondary outcomes
Time to Acquisition of a Motor Milestone
Time frame: 12 months
Survival
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
- Individual participant dataSharing planned: No
Related trials for Thymidine Kinase 2 Deficiency
RecruitingPhase 2
Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency
Thymidine Kinase 2 (TK2 ) Deficiency, Mitochondrial Myopathies
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. This study is not recruiting at the moment.
UCB Cares study director
001 844 599 2273
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MT1621 in people with Thymidine Kinase 2 Deficiency, run by Zogenix MDS, Inc..
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 3 inclusion and 4 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: withdrawn, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects acquiring a Motor Milestone (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Sep 2023.