A Phase 1/2 Clinical Study of Intravenous Gene Transfer with an AAVrh10 Vector Expressing GALC in Krabbe Subjects Receiving Hematopoietic Stem Cell Transplantation (RESKUE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Forge Biologics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2023-08-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504900-28-00

WHO UTN

U1111-1284-4113

ClinicalTrials.gov

NCT04693598

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of this clinical trial is to show that the investigational product, AAVrh.10-hGALC, is safe for administration to infantile Krabbe subjects when delivered intravenously 21 to 60 days following stem cell transplant.

Secondary objectives 1

1. The secondary objective is to collect evidence of possible therapeutic benefit of this treatment regimen.

Conditions and MedDRA coding

Krabbe Disease

Regulatory references

Scientific advice from competent authorities

The Spanish Agency Of Medicines And Medical Devices, European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of infantile Krabbe disease, characterized by the following criteria: a. Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING: b. Elevated psychosine levels predictive of infantile onset by DBS; OR c. Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR, refer to Addendum 1); OR, d. Two GALC mutations predictive to result in infantile onset phenotype
2. Age at the time of screening: 1 day to 12 months
3. Participant has been deemed eligible for treatment with HSCT (standard of care) and a fully myeloablative reduced intensity/toxicity conditioning regimen (RIC/RTC) is/has been used
4. Participant’s parents or legal guardian consents to participate in the study and provides informed consent according to IRB guidelines prior to any study procedures being performed
5. Parent(s) and/or legal guardian able to comply with the clinical protocol
6. Participant must have adequate organ function at time of screening or evaluation as measured by: a. Creatinine ≤1.5× of upper limit of age appropriate normal and creatinine clearance ≥ 60 mL/min/1.73 m2; b. Hepatic transaminases (ALT/AST) ≤ 2 x age related upper limit of normal; c. Ejection fraction of > 50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension; d. Pulmonary evaluation testing demonstrating resting pulse oximeter > 95% on room air; e. Coagulation tests within 110% of normal ranges for age. (PT/INR and PTT)

Exclusion criteria 11

1. History of prior treatment with a gene therapy product
2. Presence of major congenital anomaly or any other condition that affects neurodevelopmental function
3. Presence of any neurocognitive deficit or brain damage not attributable to Krabbe disease
4. Active aspiration
5. Signs of active infection or disease from cytomegalovirus, adenovirus or other viruses
6. HIV positive
7. Uncontrolled and progressive bacterial or fungal infection
8. Presence of any contraindication for MRI
9. Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions
10. Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the PI, would preclude participation in the study
11. Ongoing veno-occlusive disease (VOD) as determined by liver ultrasound (moderate ascites and static or retrograde portal vein flow) the day before FBX-101 infusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence and severity of adverse events and serious adverse events that are attributed to FBX-101
2. HSCT incident of engraftment

Secondary endpoints 2

1. Improvement of probability to achieve independent sitting compared to untreated patients or those receiving HSCT only at one year and two years post gene therapy
2. Improvement of gross motor function, as measured by Peabody Developmental Motor Scale 2nd Edition (PDMS-2), above a functional age equivalent of 12 months, compared to untreated patients or those receiving HSCT only, at 2 years post gene therapy

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Forge Biologics Inc.

Sponsor organisation

Forge Biologics Inc.

Address

3900 Gantz Road

City

Grove City

Postcode

43123-4834

Country

United States

Scientific contact point

Organisation

Forge Biologics Inc.

Contact name

Maria Escolar

Public contact point

Organisation

Forge Biologics Inc.

Contact name

Michelle Salvo

Sponsor responsibilities

Article 77 compliance

Forge Biologics Inc.

Contact point sponsor

Forge Biologics Inc.

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

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