Pivotal Study of N-acetyl-L-leucine for CACNA1A

NCT ID: NCT07221292

Last Updated: 2025-10-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-09-01
• Study Completion Date: 2028-11-01

Brief Summary

A pivotal, randomized, double-blind, placebo-controlled, multi-center therapeutic study for patients age 4 and older with a confirmed diagnosis of CACNA1A. The objective of this study is to evaluate the safety, tolerability and efficacy of N-acetyl-L-leucine (IB1001) compared to standard of care.

Detailed Description

This is a multinational, randomized, placebo-controlled, double-blinded, cross-over Phase III study that will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) versus Placebo for the treatment of CACNA1A Disorders.

Patients will be assessed during three study periods: a baseline period (approximately 2-weeks), after which they will be randomized (1:1) to receive treatment with IB1001 or Placebo for approximately 12-weeks during the first intervention period ("Period I"). Following Period I, patients will crossover to receive the opposite treatment (IB1001 or Placebo) for approximately 12-weeks during a second intervention period ("Period II).

Patients will be assessed twice during each study period. Patients who have participated in the study may be offered the opportunity to roll over into an Extension Phase, which is planned to allow patients to have further access to IB1001.

Conditions

CACNA1A; Spinocerebellar Ataxia Type 6; Episodic Ataxia Type 2; Familial Hemiplegic Migraine-1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

N-acetyl-L-leucine (IB1001)

Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients will receive a total daily dose of 2-4 g/day based on weight-tiered doses.

Group Type: EXPERIMENTAL

N-Acetyl-L-Leucine

Intervention Type: DRUG

N-Acetyl-L-Leucine is a modified amino-acid ester that is orally administered (granules for suspension in a sachet)

Placebo

Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients will receive a total daily dose of 2-4 g/day based on weight-tiered doses.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matching Placebo Sachet

Interventions

N-Acetyl-L-Leucine

N-Acetyl-L-Leucine is a modified amino-acid ester that is orally administered (granules for suspension in a sachet)

Intervention Type: DRUG

Placebo

Matching Placebo Sachet

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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 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, 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. 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:

1. intrauterine device (IUD);

2. surgical sterilization of the partner (vasectomy for 6 months minimum);

3. combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);

4. progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);

5. intrauterine hormone releasing system (IUS);

6. bilateral tubal occlusion.

4. Females of non-childbearing potential who have undergone one of the following sterilization procedures at least 6 months prior to the first dose:

1. hysteroscopic sterilization;

2. bilateral salpingectomy;

3. hysterectomy;

4. 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.

6. If male, patient agrees not to donate sperm from the first dose until 90 days after their last dose.

7. Patients who have ataxia symptoms which (outside of episodes, if applicable) fall within:

1. A SARA score of 7 ≤ X ≤ 34 points (out of 40) AND

2. 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. Weight ≥15 kg at screening.

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, therapy, and physiotherapy are permitted provided:

1. The Investigator does not believe the medication/therapy will interfere with the study protocol/results

2. Patients have been on a stable dose/duration and type of therapy for at least 42 days before Visit 1 (Baseline 1)

3. Patients are willing to maintain a stable dose/do not change their therapy throughout the duration of the study.

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).

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Exclusion Criteria

1. Patients who have any known hypersensitivity or history of hypersensitivity to:

1. Acetyl-Leucine (DL-, L-, D-) or derivatives.

2. Excipients the IB1001 sachet (namely isomalt, hypromellose, and strawberry flavor).

3. Excipients the placebo sachet (namely isomalt, hypromellose, strawberry flavor, citric acid, microcrystalline cellulose, lactose, denatonium benzoate).

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. 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. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.

5. Current or planned pregnancy or women who are breastfeeding.

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. 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. 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.

1. N-Acetyl-DL-Leucine (e.g. Tanganil®);

2. N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-304 trial);

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.

1. N-Acetyl-DL-Leucine (e.g. Tanganil®);

2. N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-304 trial).

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• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IntraBio Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

The University of Texas Health (UT Health)

Houston, Texas, United States

University of Cologne

Cologne, , Germany

University of Giessen

Giessen, , Germany

University Hospital Bern Inselspital

Bern, , Switzerland

Countries

United States; Germany; Switzerland

Central Contacts

Taylor Fields

Role: CONTACT

tfields@intrabio.com

+447426956369

Other Identifiers

2025-523828-51

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IB1001-304

Identifier Type: -

Identifier Source: org_study_id