A study to learn if combination pyrimidine nucleosides is safe, how well it works and how it moves through the bloodstream in participants with thymidine kinase 2 (TK2) deficiency

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UCB Biosciences Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

4 Sep 2019 → ongoing

Decision date (initial)

2024-06-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-510427-29-00

EudraCT number

2018-004277-27

WHO UTN

U1111-1304-0423

ClinicalTrials.gov

NCT03845712

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Pharmacodynamic, Efficacy

To characterize the safety and tolerability of continuing treatment with dC/dT (combination pyrimidine nucleosides, administered as doxecitine and doxribtimine) in patients with thymidine kinase 2 (TK2) deficiency previously treated with dC/dT, dCMP/dTMP or doxecitine and doxribtimine

Secondary objectives 2

1. To demonstrate the continued efficacy of dC/dT administered as doxecitine and doxribtimine
2. To evaluate the pharmacokinetics (PK) of doxecitine and doxribtimine at steady state using sparse sampling methodology

Conditions and MedDRA coding

Thymidine kinase 2 deficiency

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003210-PIP01-22

Plan to share IPD

Yes

IPD plan description

Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if a determination is made that the data cannot be adequately anonymized.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent by the parent(s) or legally authorized representative (LAR) and/or assent by the study participant (when applicable).
2. Confirmed genetic mutation(s) in the TK2 gene.
3. Absence of other genetic disease or polygenic disease.
4. Current treatment with nucleos(t)ides for TK2 deficiency. Study participants 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 for evaluating safety and efficacy.
5. Female study participants must not be breastfeeding, must have a negative pregnancy test at screening (females ≥10 years old), and have no intention to become pregnant during the course of the study. Female study participants who are of childbearing potential (ie, following menarche until ≥1 year postmenopausal if not anatomically and physiologically incapable of becoming pregnant) must agree and commit to the use of highly effective methods of birth control for the duration of the study and for 30 days after the end of the study. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (ie, <1% per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method. In certain countries (if permitted by law), women of childbearing potential may instead agree to abide by heterosexual sexual abstinence during the study and for 30 days after the end of the study.
6. Male study participants with sexual partners should use condoms for the duration of the study and for 30 days after the last dose of study drug to prevent passing study drug to the partner in the ejaculate. Male participants should be advised not to donate sperm for 30 days after the last dose of study drug.
7. Willingness to maintain current treatment regimen and current exercise regimen for the duration of the clinical study.
8. Willingness to comply with the study protocol, including but not limited to, all study procedures, study visits, and study drug compliance.

Exclusion criteria 2

1. History of liver disease, or liver function test results (ALT, AST, or total bilirubin) ≥2× upper limit of normal without prior Sponsor approval.
2. Other significant medical condition that, in the opinion of the Investigator or Study Sponsor, may confound interpretation of the clinical course of TK2 deficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of treatment-emergent adverse events (TEAEs)
2. Incidence of TEAEs leading to study drug withdrawal

Secondary endpoints 4

1. Clinical Global Impression of Improvement (CGI-I) Response score
2. Mean minimum plasma concentration (Cmin) of deoxycytidine (dC) and deoxythymidine (dT) at steady state
3. Mean maximum plasma concentration (Cmax) of dC and dT at steady state
4. Mean area under the plasma concentration - time curve from time 0 to 24 hours (AUC0-24) of dC and dT at steady state

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UCB Biosciences Inc.

Sponsor organisation

UCB Biosciences Inc.

Address

4000 Paramount Parkway Suite 200

City

Morrisville

Postcode

27560-8484

Country

United States

Scientific contact point

Organisation

UCB Biosciences Inc.

Contact name

UCB Cares

Public contact point

Organisation

UCB Biosciences Inc.

Contact name

UCB Cares

Third parties 8

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications