A Study of the Efficacy and Safety of MT1621 in Thymidine Kinase 2 (TK2) Deficiency (Treatment naïve)

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.

Study Overview

• Status: Withdrawn
• Conditions: Thymidine Kinase 2 Deficiency
• Intervention / Treatment: Drug: MT1621

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 Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Male and female Participants <18 years	Drug: MT1621; All patients will receive MT1621 up to a target dose of 400 mg/kg/day each dC and dT, as tolerated.; Other Names: Deoxycytidine (dC) and deoxythymidine (dT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects acquiring a Motor Milestone	Proportion of subjects acquiring a motor milestone not present at baseline after 12 months of MT1621 treatment.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months
Survival	Survival after 12 months of treatment	12 months

Collaborators and Investigators

• Sponsor: Zogenix MDS, Inc.
• Collaborators: Zogenix, Inc.
• Investigators: Study Director: UCB Cares, 001 844 599 2273

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2022
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: October 6, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Mitochondria; Muscle atrophy; mitochondrial disorder; mitochondrial disease; Muscle weakness; TK2; TK2d; deoxythymidine/deoxythymidine substrate enhancement therapy; dC/dT; deoxythymidine/deoxythymidine; primary mitochondrial myopathy; mitochondrial depletion syndrome; Loss of mobility; Thymidine kinase 2 deficiency
• Other Study ID Numbers: MT-1621-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No