Innovative Imaging and Cognitive BIOmarkers to Predict Huntington's Disease Progression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

21 Mar 2024 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

French Health Ministry (DGOS)

External identifiers

EU CT number

2024-516022-63-00

EudraCT number

2021-004141-20

ClinicalTrials.gov

NCT05808153

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

Identify biomarkers, used singly or in combination, that enable sensitive measurement of the progression of Huntington's disease from the presymptomatic stages onwards, within the framework of clinical trials.

Secondary objectives 2

1. Identify patient profiles and HD progression trajectories (unsupervised analyses)
2. Identify the best predictive biomarkers, individually or in combination, and establish their prognostic value on disease progression (supervised analyses)

Conditions and MedDRA coding

Patients with symptomatic and pre-symptomatic Huntington's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. For all participants: - Age ≥18 years and ≤65 years; - Information and collection of written consent; - Affiliation with a social security plan, beneficiary or beneficiary's right
2. For Healthy volunteers (control): - UHDRS functional score TFC = 13; - Motor UHDRS score TMS < 6; - With no known genetic disease and no direct relationship to an HD patient or family ancestors carrying the HD mutation (or knowing their genetic status with CAG < 36)
3. For Symptomatic huntington's disease patients: - Number of GACs ≥ 40; - CAP score ≥ 250; - 10 ≤ TFC ≤ 13; - TMS >5 if TFC=13; - Diagnostic confidence level =4; - Age of onset of disease > 20 years ; - Patient physically able to sign consent
4. For Pre-symptomatic Huntington's disease patients: - Number of GACs ≥ 40; - CAP score ≥250; - TFC = 13; - TMS < 6; - Patient physically able to sign consent

Exclusion criteria 14

1. Participant under guardianship or curatorship
2. Neurological or psychiatric disorder unrelated to HD
3. Intercurrent illness that may impact participant's performance
4. Chronic progressive neurological disease
5. Claustrophobia
6. Brain injury unrelated to HD
7. Pacemaker, intracorporeal metal, intracerebral clip, any metallic foreign body: implantable cardiac electronic device such as pacemakers, implantable cardioverter defibrillators etc., metallic intraocular foreign bodies, implantable neurostimulation systems, cochlear implants/ear implants, drug infusion pumps (insulin administration, analgesic drugs), or chemotherapy pumps): if possible, the patient should remove the device.
8. Catheters with metal components (Swan-Ganz catheter), metal fragments such as bullets, shotgun pellets and metal shrapnel, cerebral artery aneurysm clips, magnetic dental implants, tissue expander, artificial limb, hearing aid, piercing such as pacemaker
9. Known hypersensitivity to the radiopharmaceutical preparation (excipients in the radiopharmaceutical preparation)
10. Pregnant or breastfeeding woman
11. Person under state medical aid
12. Person deprived of liberty
13. Person participating or having participated in an interventional study for less than 3 months or without time limit in a trial of neural transplants or gene therapy.
14. Person participating or having participated in a research protocol with a radiopharmaceutical injection for less than 12 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be effect size, assessed by the standardized mean difference (Cohen's d) for each biomarker between the values measured initially and their assessment at 2-year follow-up.

Secondary endpoints 2

1. Analysis of patient profiles and progression trajectories, taking into account all available data at D0, M1, M1 bis, M12, M24 and M24 bis, will be based on socio-demographic characteristics, as well as initial clinical and paraclinical scores and their evolution over time. Clustering analyses will use statistical validation indices to determine the optimal number of clusters and provide information on cluster quality.
2. Identification of the best biomarkers predicting an unfavorable disease course will be carried out using conventional regression and machine learning methods. Discrimination and calibration performances will be systematically evaluated and compared for each of the models constructed.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Anne-Catherine BACHOUD-LEVI - Coordinator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Anne-Catherine BACHOUD-LEVI - Coordinator

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 14 files

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

Application history

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