A Retrospective Study of Subjects With Thymidine Kinase 2 Deficiency

• Sponsor: Modis Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05017818
• Collaborator: Zogenix, Inc. (Industry)
• Enrollment: 61
• Locations: 12
• Actual Duration (Months): 6
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Thymidine Kinase 2 Deficiency	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 Design

• Study Type: Observational
• Actual Enrollment: 61 participants
• Observational Model: Other
• Time Perspective: Retrospective
• Official Title: 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
• Actual Study Start Date: Jul 23, 2021
• Actual Primary Completion Date: Jan 21, 2022
• Actual Study Completion Date: Jan 21, 2022

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Number of participants who have died. [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.]

   Participant date of death or date last known alive.

Secondary Outcome Measures

1. Change from baseline in development motor milestones. [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.]

   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

2. Change from baseline in feeding support. [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.]

   Feeding support includes gastrostomy tube or nasogastric tube.

3. Change from baseline in respiratory support. [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.]

   Respiratory support includes non-invasive ventilation (e.g. bi-level positive airway pressure [Bi-PAP]) and mechanical ventilation.

4. Clinical Global Impression of Improvement (CGI-I). [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.]

   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.

5. 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). [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.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
2	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
3	Akron Children's Hospital	Akron	Ohio	United States	44308
4	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
5	Medical Center Zdorovyy Rebenok	Voronezh	Voronezh Oblast	Russian Federation	394077
6	NIKI Pediatrii im Veltischeva, Children's Neuromuscular center	Moscow		Russian Federation	125412
7	Vall d'Hebron Institut de Recerca	Barcelona		Spain	08035
8	Hospital Clínic Barcelona	Barcelona		Spain	08036
9	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
10	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
11	Istanbul Universitesi, Istanbul Tip Fakultesi	Fatih	Istanbul	Turkey	34093
12	Yeditepe University Koşuyolu Hospital	Kadiköy		Turkey	34178

Sponsors and Collaborators

• Modis Therapeutics, Inc.
• Zogenix, Inc.

Investigators

• Study Director: Susan VanMeter, MD, Modis Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Modis Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05017818
• Other Study ID Numbers: MT-1621-107
• First Posted: Aug 24, 2021
• Last Update Posted: Mar 11, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Modis Therapeutics, Inc.: TK2D; mitochondrial disorder; mitochondrial disease; mitochondria; primary mitochondrial myopathy; mitochondrial depletion syndrome; muscle weakness; muscle atrophy; loss of mobility

Study Results

No Results Posted as of Mar 11, 2022