A safety and efficacy extension of study HGT-MLD-070 in Children with Metachromatic Leukodystrophy recieving enzyme (HGT-1110) replacement by intrathecal injection

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shire Human Genetic Therapies Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Oct 2012 → 13 Feb 2026

Decision date (initial)

2024-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2024-514403-34-00

EudraCT number

2012-003775-20

ClinicalTrials.gov

NCT01887938

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Pharmacokinetic, Dose response, Therapy

The primary objective of this study is to collect long-term safety data in patients with MLD who are receiving HGT-1110 and have participated in Study HGT-MLD-070 through Week 40.

Secondary objectives 5

1. To evaluate the effects of IT administration of HGT-1110 on gross motor function.
2. To evaluate the effects of IT administration of HGT-1110 on adaptive behavior; as of 12 October 2021, Vineland Adaptive Behavior Scales, Second Edition (VABS-II) will not be collected.
3. To evaluate the effects of IT administration of HGT-1110 on health status and the ability to carry out activities of daily life.
4. To assess repeated-dose pharmacokinetics (PK) of HGT-1110 in serum.
5. To assess concentrations of HGT-1110 in CSF

Conditions and MedDRA coding

Late Metachromatic Leukodystrophy (MLD)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Federal Institute For Drugs And Medical Devices, Pharmaceuticals And Medical Devices Agency, European Medicines Agency

Plan to share IPD

No

IPD plan description

De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites, …)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Patient has participated in Study HGT-MLD-070 through Week 40.
2. Patient must have no safety or medical issues that contraindicate participation.
3. The patient, patient's parent or legally authorized representative(s) must provide written informed consent and/or assent (if applicable) prior to performing any study-related activities.

Exclusion criteria 13

1. The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator.
2. Undergoes bone marrow transplantation, hematopoietic stem cell transplantation, or gene therapy at any point during the study.
3. The patient has any known or suspected hypersensitivity to agents used for anesthesiaor is thought to be at an unacceptably high risk for associated potential complications of airway compromise or other conditions.
4. The patient is pregnant or breastfeeding.
5. The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or drug delivery device) other than those used in HGT-MLD-070 within 6 months prior to study enrollment or at any time during the study.
6. The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including:
7. 6a. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
8. 6b. The patient’s body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the investigator.
9. 6c. The patient has a known or suspected local or general infection.
10. 6d. The patient is at risk of abnormal bleeding due to a medical condition or therapy.
11. 6e. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation.
12. 6f. The patient has a functioning CSF shunt device.
13. 6g. The patient has shown intolerance to an implanted device.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Safety will be measured by the following endpoints: Reporting of treatment-emergent adverse events.
2. Change from baseline in clinical laboratory testing (serum chemistry including liver function tests, hematology, and urinalysis).
3. Change from baseline in vital signs, physical examinations, and CSF chemistries (including cell counts, glucose, albumin, and protein); as of 15 March 2022, CSF albumin will not be collected.
4. Determination of the presence of anti-HGT-1110 antibodies in CSF and/or serum.

Secondary endpoints 6

1. 1a. Change from baseline at end of study in motor function using the Gross Motor Function Measure-88 (GMFM-88) total score.
2. 1b. The motor function assessments (GMFM-88, global impression of motor function-change [GIMF-C], and global impression of motor function-severity [GIMF-S]) will no longer be collected when patients reach Gross Motor Function Classification System (GMFCS) level 5
3. 2. Change from baseline at end of study in the adaptive behavior composite standard score as measured by the VABS-II; as of 12 October 2021, VABS-II will not be collected
4. 3. Change from baseline at end of study in the domain-specific Caregiver Observed MLD Functioning and Outcomes Reporting Tool (COMFORT) scores
5. 4. Repeated-dose PK parameter estimates for HGT-1110 in serum
6. 5. Concentrations of HGT-1110 in CSF at selected time points after repeated investigational drug product administration

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shire Human Genetic Therapies Inc.

Sponsor organisation

Shire Human Genetic Therapies Inc.

Address

300 Shire Way

City

Lexington

Postcode

02421-2101

Country

United States

Scientific contact point

Organisation

Shire Human Genetic Therapies Inc.

Contact name

CJ Malanga

Public contact point

Organisation

Shire Human Genetic Therapies Inc.

Contact name

Takeda Medical Information

Third parties 10

Locations

5 EU/EEA countries · 13 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 25 files

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

Application history

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