A Retrospective Study of Subjects With Thymidine Kinase 2 Deficiency

A Retrospective Study of Subjects With Thymidine Kinase 2 Deficiency Treated With the Combination of Pyrimidine Nucleos(t)Ides as Well as Untreated Subjects to Collect Vital Status Data and Supporting Information

This is a multicenter, multinational, retrospective chart-review study to evaluate survival in patients with Thymidine Kinase 2 deficiency (TK2d).

Study Overview

• Status: Completed
• Conditions: Thymidine Kinase 2 Deficiency
• Intervention / Treatment: Other: Observational retrospective data

Detailed Description

This is a retrospective, chart-review study. The primary goal is to use data on survival and other related information to support a comprehensive evaluation of patients with Thymidine Kinase 2 deficiency (TK2d) who have not been treated with pyrimidine nucleos(t)ides including deoxycytidine monophosphate/deoxythymidine monophosphase (dCMP/dTMP), and deoxycytidine/deoxythymidine (dC/dT), and/or MT1621(dC/dT), and those that have received one or more of these treatments. The secondary goals of this study will focus on describing the participant's clinical course and treatment experience.

• Study Type: Observational
• Enrollment (Actual): 61

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 125412
    • NIKI Pediatrii im Veltischeva, Children's Neuromuscular center
  • Voronezh Oblast
    • Voronezh, Voronezh Oblast, Russian Federation, 394077
      • Medical Center Zdorovyy Rebenok
• Spain
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institut de Recerca
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• Turkey
  • Kadiköy, Turkey, 34178
    • Yeditepe University Kosuyolu Hospital
  • Istanbul
    • Fatih, Istanbul, Turkey, 34093
      • Istanbul Universitesi, Istanbul Tip Fakultesi
• United States
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • East Tennessee Childrens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Thymidine Kinase 2 deficiency

Description

Inclusion Criteria:

1. Signed informed consent by the subject or parent(s)/LAR and/or assent by the subject (when applicable), unless the associated IRB or EC provides an appropriate consent waiver that allows review of medical records for this study.
2. Confirmed genetic mutations in the TK2 gene.
3. Availability of medical records or information pertaining to vital status at a minimum.

Exclusion Criteria:

Not applicable as this is a non-interventional study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treated and untreated subjects with TK2 deficiency; Two TK2 deficiency groups. (1) Subjects treated with chemical-grade dCMP/dTMP, dC/dT, and/or MT1621 outside of a Modis sponsored study. (2) Subjects not treated with chemical-grade dCMP/dTMP, dC/dT, and/or MT1621 outside of a Modis sponsored study.	Other: Observational retrospective data; Non-intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who have died.	Participant date of death or date last known alive.	Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in development motor milestones.	Modified motor milestones as defined by World Health Organization include: Ability to Hold head upright, unassisted; Ability to roll from supine to sides; Ability to sit upright, unassisted; Ability to sit upright, slightly assisted; Ability to raise self and stand; Ability to stand, unassisted; Ability to stand, assisted; Ability to walk, unassisted; Ability to walk, assisted; Ability to climb stairs, unassisted; Ability to climb stairs, assisted; Ability to jump; Ability to hop; Ability to run	Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first.
Change from baseline in feeding support.	Feeding support includes gastrostomy tube or nasogastric tube.	Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first.
Change from baseline in respiratory support.	Respiratory support includes non-invasive ventilation (e.g. bi-level positive airway pressure [Bi-PAP]) and mechanical ventilation.	Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first.
Clinical Global Impression of Improvement (CGI-I).	The CGI-I is a 7-point Likert scale would have been conducted by a physician or trained rater at a clinic visit to establish overall clinical change.	Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first.
Number of participants with treatment-emergent adverse events (AEs) or serious adverse events (SAEs) that cause a decrease in dose or a stop in dosing (temporary or permanent).	An AE is any untoward medical occurrence in a participant that was receiving treatment without regard to causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. SAEs were AEs excluding non-serious AEs.	Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2021
• Primary Completion (Actual): January 21, 2022
• Study Completion (Actual): January 21, 2022

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 24, 2021

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: muscle weakness; mitochondria; muscle atrophy; mitochondrial disorder; mitochondrial disease; primary mitochondrial myopathy; mitochondrial depletion syndrome; TK2D; loss of mobility
• Other Study ID Numbers: MT-1621-107

Drug and device information, study documents

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