MT1621 for TK2 Deficiency

(Continuation Trial)

Recruiting at 14 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Zogenix MDS, Inc.

Must be taking: Nucleos(t)ides

Disqualifiers: Liver disease, other significant condition

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 3 years

47 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to continue their current treatment with nucleos(t)ides for TK2 deficiency throughout the study.

Is MT1621 safe for humans?

The research does not provide specific safety data for MT1621 in humans, but it mentions a treatment involving deoxycytidine and deoxythymidine monophosphates that showed positive effects in a mouse model of TK2 deficiency, suggesting potential safety and effectiveness in animals. ^{1 2 3 4 5}

How does the drug MT1621 differ from other treatments for TK2 deficiency?

MT1621 is unique because it uses a combination of deoxycytidine and deoxythymidine monophosphates to bypass the deficiency in the TK2 enzyme, which helps restore balance in the building blocks needed for mitochondrial DNA. This approach is the first effective pharmacologic treatment for TK2 deficiency, significantly improving symptoms and extending lifespan in preclinical models. ^{1 2 3 4 5}

Research Team

UCB Cares

Principal Investigator

001 844 599 2273

Eligibility Criteria

This trial is for patients with TK2 deficiency who have a confirmed genetic mutation in the TK2 gene, are not pregnant or breastfeeding, agree to use contraception, and can maintain their current treatment and exercise regimens. They must not have liver disease or certain other medical conditions that could affect study results.

Inclusion Criteria

My condition involves a confirmed TK2 gene mutation.

Current treatment with nucleos(t)ides for TK2 deficiency. Patients who were not previously enrolled in MT 1621 101 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

I am not pregnant, breastfeeding, or planning to become pregnant and agree to use effective birth control.

Exclusion Criteria

I don't have any health issues that could affect my TK2 deficiency study results.

My liver function tests are normal or I have approval for higher levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxecitine and doxribtimine up to a maximum of 800 mg/kg/day

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MT1621

Trial Overview The safety and effectiveness of two drugs, doxecitine and doxribtimine, are being tested in individuals with thymidine kinase 2 (TK2) deficiency. This Phase 2 trial is open-label, meaning both researchers and participants know which treatment is given.

Participant Groups

Group I: doxecitine and doxribtimine Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

Zogenix MDS, Inc.

Lead Sponsor

Trials

4

Recruited

150+

Modis Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

150+

UCB BIOSCIENCES, Inc.

Lead Sponsor

Trials

28

Recruited

7,200+

Zogenix, Inc.

Industry Sponsor

Trials

25

Recruited

2,600+

Findings from Research

Supplementation with deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) in a mouse model of thymidine kinase 2 (TK2) deficiency significantly increased mitochondrial DNA levels and improved mitochondrial function, leading to a prolonged lifespan from 13 days to 34 days with treatment.

This study represents the first effective pharmacological treatment for TK2 deficiency, demonstrating that dCMP/dTMP can effectively bypass the enzyme deficiency and ameliorate biochemical defects associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency. Garone, C., Garcia-Diaz, B., Emmanuele, V., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Application of oligonucleotide array CGH to the simultaneous detection of a deletion in the nuclear TK2 gene and mtDNA depletion. [2009]

2. Italy pubmed.ncbi.nlm.nih.gov

Mild myopathic phenotype in a patient with homozygous c.416C > T mutation in TK2 gene. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Late-onset thymidine kinase 2 deficiency: a review of 18 cases. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Recurrent rhabdomyolysis and exercise intolerance: A new phenotype of late-onset thymidine kinase 2 deficiency. [2021]