A RETROspective Study of Patients With TK2d (RETRO)

A RETROspective Study of the Combination of Pyrimidine Nucleos(t)Ides in Patients With Thymidine Kinase 2 Deficiency (TK2)

This is a medical chart review study to collect information for patients who have been taking pyrimidine nucleosides for treatment of TK2 deficiency. Information from the time of onset of symptoms will be collected to describe the pre treatment course of TK2 deficiency.

Study Overview

• Status: Completed
• Conditions: Thymidine Kinase 2 (TK2)
• Intervention / Treatment: Drug: dC/dT

Detailed Description

Data to be collected from the time of onset of symptoms related to TK2 deficiency includes medical conditions and/or adverse events (AEs); these should include relationship to TK2 disease and/or pyrimidine nucleosides, as appropriate, as well as date of onset and severity, when available. When available, test reports may be obtained as well as available research biological samples (eg, blood or tissue samples that may be tested for biomarkers of disease and/or effects of medications to treat the mitochondrial disease).

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Rambam Hospital
  • Holon, Israel, 5822012
    • Wolfson Medical Center
  • Nahariya, Israel, 89 כביש
    • Western Galilee Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08950
    • Sant Joan de Deu Hospital
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

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 TK2 deficiency who have received treatment with pyrimidine nucleosides

Description

Inclusion Criteria:

1. Signed informed consent by the patient or parent(s)/legally authorized representative (LAR) and/or assent by the patient (when applicable), unless the associated institutional review board (IRB) or ethics committee (EC) provides an appropriate consent waiver
2. Confirmed genetic mutation in the TK2 gene
3. Availability of medical records for each patient from the time of onset of symptoms
4. Patient has taken pyrimidine nucleos(t)ides (dCMP/dTMP and/or dC/dT) as substrate enhancement therapy for TK2 deficiency
5. Most recent patient visit at which efficacy and/or safety parameters were collected occurred between 01 June 2018 and 15 December 2018

Exclusion Criteria:

1. Presence of other genetic disease or polygenic disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis	genetic testing (previously conducted)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical course	BMI (height in inches and weight in kg will be combined to report BMI in kg/m^2)	3 months
Clinical course	achievement, loss, or regaining of developmental motor milestones	3 months
Motor function and ambulatory assessments	Change in 6-minute walk test [6MWT] distance (in meters)	3 months
Motor function and ambulatory assessments	Motor Function Measure [MFM] 20 or MFM 32	3 months
Motor function and ambulatory assessments	Egen Klassifikation	3 months
Motor function and ambulatory assessments	North Star Ambulatory Assessment	3 months
Motor function and ambulatory assessments	Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]	3 months
Motor function and ambulatory assessments	Hammersmith Functional Motor Scale-Expanded [HFMSE]	3 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2018
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 10, 2018

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: myopathy, muscle weakness, hypotonia, dysphagia, ptosis
• Other Study ID Numbers: MT-1621-101

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