A pivotal study of N-Acetyl-L-Leucine on CACNA1A Disorders

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intrabio Limited, IntraBio Inc

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-04-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

IntraBio Ltd

External identifiers

EU CT number

2025-523828-51-00

ClinicalTrials.gov

NCT07221292

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

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 CACNA1A disorders.

Secondary objectives 1

1. o To assess the clinical efficacy of N-Acetyl-L-Leucine on neurological signs, symptoms, functioning, and quality of life for patients with CACNA1A disorders; o To evaluate the safety and tolerability of N-Acetyl-L-Leucine in weight-tiered doses in patients with CACNA1A disorders

Conditions and MedDRA coding

CACNA1A Disorders

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Food And Drug Administration, National Authority Of Medicines And Health Products, Federal Institute For Drugs And Medical Devices, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Written informed consent signed by the patient and/or their legal representative/ parent/ impartial witness
2. 2. Male or female aged ≥4 years with a genetically confirmed diagnosis of a CACNA1A disorder (including patients with loss-of-function and fain-of-function mutations, e.g. Episodic Ataxia Type 2 [EA2], Familial Hemiplegic Migraine Type 1 [FHM1], Spinocerebellar Ataxia type C (SCA6), Developmental and Epileptic encephalopathy 42 (DEE42), Congenital ataxia or cerebellar hypoplasia due to a CACNA1A mutation ) at the time of signing informed consent
3. 3. Females of childbearing potential, defined as a premenopausal female capable of becoming pregnant, will be included if they are either sexually inactive (sexually abstinent for 14 days prior to the first dose and confirm to continue through 28 days after the last dose) or using one of the following highly effective contraceptives (i.e. results in <1% failure rate when used consistently and correctly) 14 days prior to the first dose continuing through 28 days after the last dose: a) intrauterine device (IUD); b) surgical sterilization of the partner (vasectomy for 6 months minimum); c) combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal); d) progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable); e) intrauterine hormone releasing system (IUS); f) bilateral tubal occlusion.
4. 4. Females of non-childbearing potential who have undergone one of the following sterilization procedures at least 6 months prior to the first dose: a) hysteroscopic sterilization; b) bilateral salpingectomy; c) hysterectomy; d) bilateral oophorectomy; OR be postmenopausal with amenorrhea for at least 1 year prior to the first dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status. FSH analysis for postmenopausal women will be done at screening. FSH levels should be in the postmenopausal range as determined by the central laboratory.
5. 5. Non-vasectomized male patient agrees to use a condom with spermicide until 90 days beyond the last dose of study medication and the female partner agrees to comply with inclusion criteria 3 or 4. For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male
6. 6. If male, patient agrees not to donate sperm from the first dose until 90 days after their last dose.
7. 7. Patients who have ataxia symptoms which (outside of episodes, is applicable) 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.
8. 8. Weight ≥15 kg at screening
9. 9. Patients are willing to disclose their existing medications/therapies for (the symptoms of) CACNA1A disorder including those on the prohibited medication list. Non-prohibited medications/therapies (e.g. speech therapy, physiotherapy) are permitted provided: a) The Investigator does not believe the medication/therapy will interfere with the study protocol/results b) Patients have been on a stable dose/duration and type of therapy for at least 42 days before Visit 1 (Baseline 1) c) Patients are willing to maintain a stable dose/do not change their therapy throughout the duration of the study.
10. 10. An understanding of the implications of study participation, provided in the written patient information and informed consent by patients or their legal representative/parent, and demonstrates a willingness to comply with instructions and attend required study visits (for children this criterion will also be assessed in parents or appointed guardians).

Exclusion criteria 9

1. 1. Patients who have any known hypersensitivity or history of hypersensitivity to: a. Acetyl-Leucine (DL-, L-, D-) or derivatives. b. Excipients the IB1001 sachet (namely isomalt, hypromellose, and strawberry flavor). c. Excipients the placebo sachet (namely isomalt, hypromellose, strawberry flavor, citric acid, microcrystalline cellulose, lactose, denatonium benzoate).
2. 2. Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product (IMP; ‘study drug’) for at least 42 days prior to Visit 1. At the discretion of the Investigator, Medical Monitor, and Sponsor, the washout period for specific IMPs may be longer based on the pharmacological activity and pharmacokinetics of the drug.
3. 3. Patients with a physical, cognitive, 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. 4. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.
5. 5. Current or planned pregnancy or women who are breastfeeding.
6. 6. Patients with severe vision or hearing impairment (that is not corrected by glasses or hearing aids) that, at the Investigator’s discretion, interferes with their ability to perform study assessments
7. 7. Patients who have been diagnosed with arthritis or other musculoskeletal disorders affecting joints, muscles, ligaments, and/or nerves that by themselves affect patient’s mobility and, at the Investigator’s discretion, interferes with their ability to perform study assessments.
8. 8. Patients at non-EU trial sites unwilling and/or not able to undergo a 42-day washout period from any of the following prohibited medication prior to Visit 1 (Baseline 1) and remain without prohibited medication through Visit 6. a. N-Acetyl-DL-Leucine (e.g. Tanganil®); b. N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-304 trial);
9. 9. Patients at EU trial sites who have had any of the following prohibited medication 42-days prior to Visit 1 (Baseline 1) and unwilling and/or not able to remain without prohibited medication through Visit 6. a. N-Acetyl-DL-Leucine (e.g. Tanganil®); b. N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-304 trial).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint measure is the Scale for the Assessment and Rating of Ataxia (SARA). SARA is an eight-item clinical rating scale (range 0–40, where 0 is the best neurological status and 40 the worst). It is a reliable and valid clinical scale with a high internal consistency that measures the severity of ataxia and increases with ataxia disease stage.

Secondary endpoints 1

1. • Spinocerebellar Ataxia Functional Index (SCAFI) • Functional Scale for the Assessment and Rating of Ataxia (f-SARA) [US only - key secondary endpoint in the US] • Quality of Life EQ-5D-5L for patients aged ≥18; EQ-5D-Y for children aged <18 years • Neuro Quality of Life – Upper Extremity Function (NeuroQOL-UEF) assessed by the Patient or the Caregiver (if patient unable to complete)

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

Summit House, 170 Finchley Road 170 Finchley Road

City

London

Postcode

NW3 6BP

Country

United Kingdom

Scientific contact point

Organisation

Intrabio Limited

Contact name

Taylor Fileds

Public contact point

Organisation

Intrabio Limited

Contact name

Taylor Fileds

Third parties 10

IntraBio Inc

Sponsor organisation

IntraBio Inc

Address

201 West 5th Street, Suite 1100 Suite 1100

City

Austin

Postcode

TX 78701

Country

United States

Scientific contact point

Organisation

IntraBio Inc

Contact name

Taylor Fields

Public contact point

Organisation

IntraBio Inc

Contact name

Taylor Fields

Third parties 10

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 113 files

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

Application history

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