NCT06174220

Brief Summary

The TaRGET study is a multi-centre, prospective, randomized, double-blind, placebo-controlled trial designed to evaluate the potential therapeutic efficacy of tideglusib, a glycogen synthase kinase-3 β inhibitor, in genotype positive arrhythmogenic cardiomyopathy.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_2

Timeline
14mo left

Started Mar 2025

Geographic Reach
1 country

17 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress50%
Mar 2025Jul 2027

First Submitted

Initial submission to the registry

December 1, 2023

Completed
17 days until next milestone

First Posted

Study publicly available on registry

December 18, 2023

Completed
1.3 years until next milestone

Study Start

First participant enrolled

March 21, 2025

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2027

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2027

Last Updated

March 12, 2026

Status Verified

April 1, 2025

Enrollment Period

1.9 years

First QC Date

December 1, 2023

Last Update Submit

March 10, 2026

Conditions

Arrhythmogenic CardiomyopathyArrhythmogenic Right Ventricular Cardiomyopathy

Keywords

sudden cardiac death, ventricular cardiomyopathy, genetics, arrhythmia

Outcome Measures

Primary Outcomes (1)

  • PVC burden

    Change in mean PVC count per 24 hours on 7-day Holter

    Baseline and 6 months

Secondary Outcomes (3)

  • Ventricular strain

    Baseline and 6 months

  • Implantable cardioverter-defibrillator (ICD) therapies

    Baseline and 6 months

  • Sustained ventricular tachycardia (VT) events

    Baseline and 6 months

Study Arms (2)

Tideglusib

ACTIVE COMPARATOR

Randomization to Tideglusib 1g po daily or matching placebo

Drug: Tideglusib

Placebo

PLACEBO COMPARATOR

Randomization to matching placebo 1g po daily

Drug: Placebo

Interventions

TideglusibDRUG

Tideglusib 1g po daily

Tideglusib
PlaceboDRUG

Matching placebo 1g po daily

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A pathogenic or likely pathogenic desmosomal (PKP2, DSG2, DSC2, DSP, or JUP\*) rare variant OR the TMEM43-p.S358L variant
  • \*JUP carriers must be homozygous or compound heterozygous
  • Mean ≥ 500 PVCs per 24 hours on a baseline screening 7-day Holter monitor
  • Clinical ACM diagnosis or recognition of genetic carrier status for ≥ 6 months prior to screening

You may not qualify if:

  • NYHA class IV heart failure
  • Ventricular scar secondary to coronary artery disease
  • Initiation, cessation, or dose change of a Class I or III anti-arrhythmic drug in the 3 months prior to screening
  • Any potentially harmful chronic liver disease
  • ALT value \> 2X the upper limit of the normal reference range at Screening
  • Total bilirubin value greater than the upper limit of the normal reference range at Screening, unless documented Gilbert's syndrome. For individuals with Gilbert's syndrome, total bilirubin value greater than 2-fold the upper limit of the normal reference range at Screening.
  • A history of alcohol or illicit substance use disorders
  • Regular and long-term use of strong CYP3A4 inhibitors, including clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir
  • Serum creatinine \> 150 micromole/L or creatinine clearance ≤ 60 mL/min (according to Cockcroft-Gault formula) at Screening
  • Pregnant at time of enrollment and women of childbearing age who do not use a highly effective form of contraception
  • Males, engaged in sexual relations with a female of child-bearing potential, not using an acceptable contraceptive method if not surgically sterile
  • Patients unwilling to provide informed consent or comply with follow-up
  • Hypersensitivity to tideglusib or any components of its formulation, including allergy to strawberry
  • Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window e.g. warfarin and digoxin

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

University of British Columbia

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

Victoria Cardiac Arrhythmia Trials Inc.

Victoria, British Columbia, V8Z 0B9, Canada

RECRUITING

NL Health Services

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

RECRUITING

Nova Scotia Health

Halifax, Nova Scotia, B3H 2Y9, Canada

RECRUITING

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

NOT YET RECRUITING

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

RECRUITING

Newmarket Electrophysiologist Research Group 'NERG'

Newmarket, Ontario, L3Y 2P9, Canada

NOT YET RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

NOT YET RECRUITING

Heart Health Institute Research Inc

Scarborough Village, Ontario, M1E 4B9, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

NOT YET RECRUITING

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

NOT YET RECRUITING

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

NOT YET RECRUITING

Hopital du Sacré-Coeur de Montréal

Montreal, Quebec, H4J 1C5, Canada

NOT YET RECRUITING

University Institute of Cardiology and Pneumology of Quebec

Québec, Quebec, G1V 4G5, Canada

RECRUITING

Related Publications (5)

  • Krahn AD, Wilde AAM, Calkins H, La Gerche A, Cadrin-Tourigny J, Roberts JD, Han HC. Arrhythmogenic Right Ventricular Cardiomyopathy. JACC Clin Electrophysiol. 2022 Apr;8(4):533-553. doi: 10.1016/j.jacep.2021.12.002.

    PMID: 35450611BACKGROUND

  • Asimaki A, Kapoor S, Plovie E, Karin Arndt A, Adams E, Liu Z, James CA, Judge DP, Calkins H, Churko J, Wu JC, MacRae CA, Kleber AG, Saffitz JE. Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Sci Transl Med. 2014 Jun 11;6(240):240ra74. doi: 10.1126/scitranslmed.3008008.

    PMID: 24920660BACKGROUND

  • Chelko SP, Asimaki A, Andersen P, Bedja D, Amat-Alarcon N, DeMazumder D, Jasti R, MacRae CA, Leber R, Kleber AG, Saffitz JE, Judge DP. Central role for GSK3beta in the pathogenesis of arrhythmogenic cardiomyopathy. JCI Insight. 2016 Apr 21;1(5):e85923. doi: 10.1172/jci.insight.85923.

    PMID: 27170944BACKGROUND

  • Roberts JD, Murphy NP, Hamilton RM, Lubbers ER, James CA, Kline CF, Gollob MH, Krahn AD, Sturm AC, Musa H, El-Refaey M, Koenig S, Aneq MA, Hoorntje ET, Graw SL, Davies RW, Rafiq MA, Koopmann TT, Aafaqi S, Fatah M, Chiasson DA, Taylor MR, Simmons SL, Han M, van Opbergen CJ, Wold LE, Sinagra G, Mittal K, Tichnell C, Murray B, Codima A, Nazer B, Nguyen DT, Marcus FI, Sobriera N, Lodder EM, van den Berg MP, Spears DA, Robinson JF, Ursell PC, Green AK, Skanes AC, Tang AS, Gardner MJ, Hegele RA, van Veen TA, Wilde AA, Healey JS, Janssen PM, Mestroni L, van Tintelen JP, Calkins H, Judge DP, Hund TJ, Scheinman MM, Mohler PJ. Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy. J Clin Invest. 2019 Jul 2;129(8):3171-3184. doi: 10.1172/JCI125538. eCollection 2019 Jul 2.

    PMID: 31264976BACKGROUND

  • Padron-Barthe L, Villalba-Orero M, Gomez-Salinero JM, Dominguez F, Roman M, Larrasa-Alonso J, Ortiz-Sanchez P, Martinez F, Lopez-Olaneta M, Bonzon-Kulichenko E, Vazquez J, Marti-Gomez C, Santiago DJ, Prados B, Giovinazzo G, Gomez-Gaviro MV, Priori S, Garcia-Pavia P, Lara-Pezzi E. Severe Cardiac Dysfunction and Death Caused by Arrhythmogenic Right Ventricular Cardiomyopathy Type 5 Are Improved by Inhibition of Glycogen Synthase Kinase-3beta. Circulation. 2019 Oct;140(14):1188-1204. doi: 10.1161/CIRCULATIONAHA.119.040366. Epub 2019 Sep 5.

    PMID: 31567019BACKGROUND

MeSH Terms

Conditions

Arrhythmogenic Right Ventricular DysplasiaDeath, Sudden, CardiacArrhythmias, Cardiac

Interventions

tideglusib

Condition Hierarchy (Ancestors)

Heart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesCardiomyopathiesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHeart ArrestDeath, SuddenDeathPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Jason D Roberts, MD MAS

    McMaster University and Population Health Research Institute

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason Roberts, MD MAS

CONTACT

905-521-2100jason.roberts@phri.ca

Maha Mushtaha

CONTACT

maha.mushtaha@phri.ca

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Patients will be randomized in a 1:1 ratio using an automated central, web-based system within 30 days of completing their baseline Holter. Randomization will be stratified by TMEM43-p.S358L variant status.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 1, 2023

First Posted

December 18, 2023

Study Start

March 21, 2025

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

July 1, 2027

Last Updated

March 12, 2026

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations

CA(17)