Phase I/II Safety and Tolerability Study of striatal administration of AB-1001 in adult subjects with Early Manifest Huntington's Disease (HD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AskBio France

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Nov 2024 → ongoing

Decision date (initial)

2024-03-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AskBio France

External identifiers

EU CT number

2024-510895-18-00

EudraCT number

2021-003052-16

ClinicalTrials.gov

NCT05541627

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety

Assess the safety and tolerability of a one- time, bilateral administration of AB-1001 into the caudate nucleus and putamen; Select the dose of AB-1001 to be utilized in the Expansion Part

Secondary objectives 1

1. Assess key biomarkers and preliminary efficacy

Conditions and MedDRA coding

Huntington's disease

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Agence Nationale De Securite Du Medicament Et Des Produits De Sante (ANSM)

Plan to share IPD

No

IPD plan description

Population of trial subjects

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or Female subjects between ages 18 and 65 years (both inclusive) at time of consenting, able to provide Informed Consent and able to understand and comply with all study procedures.
2. Documented genetic confirmation of pathological CAG expansion in the huntingtin gene ≥ 40
3. Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and a diagnostic classification level (DCL) of 4, or a DCL of 3 if present with cognitive impairment and clear evidence of disease progression.
4. Striatal MRI volumes per hemisphere compatible with the local delivery of the study drug: Putamen ≥ 2.3 cm3 (per side); Caudate ≥ 1.7 cm3 on Screening MRI.
5. All HD concomitant medications are stable for at least 30 days prior to screening at the investigator’s discretion.

Exclusion criteria 8

1. Subjects with prior metastatic neoplasms
2. Subjects with active psychosis
3. Subjects with confused state
4. Subjects with violent and/or suicidal behavior
5. Subjects with prior strokes
6. Subjects with intracranial hemorrhage
7. Subjects with active infection
8. Subjects with contraindication to MRI or gadolinium and any other medical condition that in the investigator’s opinion would interfere with the study conduct and assessments will be excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of Dose Limiting Toxicities (DLTs), Treatment Emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs) through Week 52

Secondary endpoints 5

1. Magnitude and variability of change from baseline in anatomical and volumetric measures of brain regions impacted by HD (caudate, putamen, whole brain volume, grey matter volume, white matter volume, ventricular volume) as assessed by MRI at Week 52
2. Change from baseline in the Unified Huntington’s Disease Rating Scale composite score [cUHDRS: Total Motor Score (TMS), Total Functional Capacity (TFC), Symbol Digit Modalities Test (SDMT) and Stroop Word Reading (SWRT)] at Week 52
3. Change from baseline in blood and cerebrospinal fluid (CSF) mHTT, Neurofilament light chain (NfL), and 24-OH cholesterol at Week 52
4. Change from baseline in Magnetic Resonance Spectroscopy (MRS) metabolic profile (measuring lactate, N-acetyl aspartate, creatine, choline, glutamate, glutamine, glutathione, taurine, and myo-inositol) at Week 52
5. Change from baseline in Positron Emission Tomography (PET) Fluoro-deoxyglucose (FDG) striatal profile at Week 52

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AskBio France

Sponsor organisation

AskBio France

Address

47 Boulevard De L Hopital

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

AskBio France

Contact name

Huntington Study France Information

Public contact point

Organisation

AskBio France

Contact name

Huntington Study France Information

Third parties 7

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 8 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