Effects of N-Acetyl-L-Leucine on Niemann-Pick disease type C (NPC): A Phase III, randomized, placebo-controlled, double-blind, crossover study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intrabio Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

16 Jun 2022 → ongoing

Decision date (initial)

2024-03-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-510278-14-00

EudraCT number

2021-005356-10

ClinicalTrials.gov

NCT05163288

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

The primary objective is to evaluate the efficacy of N-Acetyl-L-Leucine based on the Scale for the Assessment and Rating of Ataxia (SARA) for the chronic treatment of NPC

Secondary objectives 2

1. o To assess the clinical efficacy of N-Acetyl-L-Leucine on symptoms, functioning, and quality of life for patients with NPC
2. o To evaluate the safety and tolerability of N-Acetyl-L-Leucine at 4 g/day in NPC patients aged ≥13 years, and weight-tiered doses in NPC patients aged 4 to 12 years of age

Conditions and MedDRA coding

Niemann-Pick disease type C

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Food And Drug Administration, Servico de Saude da Regiao Autonoma Da Madeira EPERAM, Medicines Evaluation Board, Federal Institute For Drugs And Medical Devices

EMA paediatric investigation plan (PIP)

EMEA-002796-PIP01-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Written informed consent signed by the patient and/or their legal representative/ parent/ impartial witness
2. Male or female aged ≥4 years with a confirmed diagnosis of NPC at the time of signing informed consent
3. Patients must fall within: a) A SARA score of 7 ≤ X ≤ 34 points (out of 40) AND b) Either: i. Within the 2-7 range (0-8 range) of the Gait subtest of the SARA scale OR ii. Be able to perform the 9-Hole Peg Test with Dominant Hand (9HPT-D) (SCAFI subtest) in 20 ≤ X ≤150 seconds.
4. Weight ≥15 kg at screening

Exclusion criteria 4

1. Patients who have any known hypersensitivity or history of hypersensitivity to Acetyl leucine (DL, L, D) or derivatives, and or Excipients in the IB1001 or placebo sachets
2. Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product
3. Patients with a physical or psychiatric condition which, at the investigator’s discretion and in consultation with the Medical Monitor and Sponsor (as applicable), may put the patient at risk, may confound the study results, or may interfere with the patient’s participation in the clinical study, i.e. reliably perform study assessments
4. Patients who have been diagnosed with arthritis or other musculoskeletal disorders affecting joints, muscles, ligaments, and/or nerves that by themselves affects patient’s mobility and, at the investigator’s discretion, interferes with their ability to perform study assessments

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint for the study is of the Scale for the Assessment and Rating of Ataxia (SARA). In the US, the Modified SARA is the primary endpoint.

Secondary endpoints 4

1. Spinocerebellar Ataxia Functional Index (SCAFI)
2. Quality of Life EQ-5D-5L for patients aged ≥18; EQ-5D-Y for patients aged <18 years
3. Modified Disability Rating Scale (mDRS)
4. Physician’s, Caregiver’s (if applicable), and Patient’s (if able) Clinical Global Impression of Improvement (CGI-I) comparing end of period I (Visit 4) to baseline (Visit 2), and end of period II (Visit 6) to end of period I (Visit 4

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intrabio Limited

Sponsor organisation

Intrabio Limited

Address

Centre For Innovation & Enterprise, Begbroke Science Park, Begbroke Hill, Yarnton Begbroke Science Park Begbroke Hill

City

Kidlington

Postcode

OX5 1PF

Country

United Kingdom

Scientific contact point

Organisation

Intrabio Limited

Contact name

Taylor Fields

Public contact point

Organisation

Intrabio Limited

Contact name

Taylor Fields

Locations

4 EU/EEA countries · 6 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 155 files

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

Application history

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