N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T)

NCT03759678 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IB1001-203
• Study Type: interventional
• Target: 17
• Locations: 4 countries
• Sites: 4

Brief Summary

This is a multinational, multicenter, open-label, rater-blinded prospective Phase II study which will assess the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the treatment of Ataxia-Telangiectasia (A-T). There are two phases to this study: the Parent Study, and the Extension Phase. The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the symptomatic treatment of A-T. The Extension Phase evaluates the long-term safety and efficacy of IB1001 for the neuroprotective, disease-modifying treatment of A-T.

Conditions

Ataxia Telangiectasia

Outcome Measures

Primary Outcomes (1)

• Clinical Impression of Change in Severity (CI-CS) [Fields et al. 2021]

  The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or 8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video? The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse). Change values were calculated for each period, i.e. treatment with IB1001 (comparing the end of treatment (Visit 4) with baseline (Visit 2)) and post-treatment washout (comparing the end of washout (Visit 6) with the end of treatment (Visit 4)). Then, the mean change obtained in the post-treatment period was subtracted from the mean change obtained for the treatment with IB1001 period, with a positive value indicating an improvement in the treatment period compared to the post-treatment washout period.

  CI-CS comparing Baseline (Day 1) with IB1001 versus the end of 6-weeks treatment with IB1001 (Approximately Day 42) MINUS the CI-CS comparing the end of 6-weeks treatment with IB1001 (Approximately Day 42) versus the end of 6-weeks post-treatment washout

Secondary Outcomes (9)

• Key Secondary Endpoint: Change in Severity Based on Average CI-S

  (CI-S comparing baseline period [average for Visit 1 and 2] and end of treatment period [average for Visit 3 and 4]) MINUS (change in CI-S between end of treatment period [average for Visit 3 and 4] and end of washout period [average for Visit 5 and 6])

• Secondary Efficacy Endpoint: Individual Components of CI-CS

  Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout.

• Secondary Efficacy Endpoint: CI-CS Score Reclassified on a 3-Point Scale

  Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout

• Secondary Efficacy Endpoint: CI-CS Score for the Non-Primary Anchor Test

  CI-CS of the non-primary anchor test was evaluated, comparing the CI-CS of Visit 4 (end of treatment) versus Visit 2 (baseline) and of Visit 6 (end of washout) versus Visit 4 (end of treatment) as done for the primary anchor test.

• Secondary Efficacy Endpoint: Change in the Scale for Assessment and Rating of Ataxia (SARA) Score [Schmitz-Hübsch Etal, 2006; Subramony, 2007]

  Baseline (Day 1) to end of treatment with IB1001 (Approximately Day 42); End of treatment with IB1001 (Approximately Day 42) to the end of post-treatment washout (Approximately Day 84)

Study Arms (2)

Treatment with IB1001

EXPERIMENTAL

6-weeks treatment with IB1001 administered orally. Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old will receive weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg will take 2 g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg will take 3 g per day: 1 g in the morning, 1 g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg will take 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults) After the 6-week treatment period, patients will enter a 6-week post-treatment washout period.

Drug: IB1001

Post-Treatment Washout

NO INTERVENTION

After the 6-week treatment period, patients will enter a 6-week post-treatment washout period.

Interventions

IB1001 DRUG

IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered.

Also known as: N-Acetyl-L-Leucine

Treatment with IB1001

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals who meet all of the following criteria are eligible to participate in the study:
• Written informed consent signed by the patient and/or their legal representative/ parent
• Male or female aged ≥6 years with a confirmed diagnosis of A-T at the time of signing informed consent.
• 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 continuing 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:
• intrauterine device (IUD);
• surgical sterilization of the partner (vasectomy for 6 months minimum);
• combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal);
• progestogen-only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable);
• intrauterine hormone-releasing system (IUS);
• bilateral tubal occlusion.
• Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
• hysteroscopic sterilization;
• bilateral tubal ligation or bilateral salpingectomy;
• hysterectomy;
• bilateral oophorectomy;

You may not qualify if:

• Individuals who meet any of the following criteria are not eligible to participate in the study:
• Asymptomatic patients
• Patient has clinical features of A-T, but a completely negative result on a previous genetic test for A-T.
• Patients who have any of the following:
• Chronic diarrhea;
• Unexplained visual loss;
• Malignancies;
• Insulin-dependent diabetes mellitus.
• Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or derivatives.
• History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose, sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan, dimethicone, methylparaben, and potassium sorbate).
• Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product (IMP; 'study drug') within 6 weeks prior to Visit 1.
• Patients with a physical or psychiatric condition which, at the investigator's discretion, may put the patient at risk, may confound the study results, or may interfere with the patient's participation in the clinical study.
• Known clinically-significant (at the discretion of the investigator) laboratories in hematology, coagulation, clinical chemistry, or urinalysis, including, but not limited to:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5x upper limit of normal (ULN);
• Total bilirubin \>1.5x ULN, unless Gilbert's syndrome is present in which case total bilirubin \>2x ULN.

Sponsors & Collaborators

• IntraBio Inc: lead

Study Sites (4)

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

University of Giessen

Giessen, Germany

Location

Hospital Universitario La Paz

Madrid, Spain, Spain

Location

Royal Papworth Hospital NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0AY, United Kingdom

Location

Related Publications (3)

• Brueggemann A, Bicvic A, Goeldlin M, Kalla R, Kerkeni H, Mantokoudis G, Abegg M, Kolnikova M, Mohaupt M, Bremova-Ertl T. Effects of Acetyl-DL-Leucine on Ataxia and Downbeat-Nystagmus in Six Patients With Ataxia Telangiectasia. J Child Neurol. 2022 Jan;37(1):20-27. doi: 10.1177/08830738211028394. Epub 2021 Oct 7.

  PMID: 34620022 DERIVED

• Churchill GC, Strupp M, Factor C, Bremova-Ertl T, Factor M, Patterson MC, Platt FM, Galione A. Acetylation turns leucine into a drug by membrane transporter switching. Sci Rep. 2021 Aug 4;11(1):15812. doi: 10.1038/s41598-021-95255-5.

  PMID: 34349180 DERIVED

• Fields T, Patterson M, Bremova-Ertl T, Belcher G, Billington I, Churchill GC, Davis W, Evans W, Flint S, Galione A, Granzer U, Greenfield J, Karl R, Kay R, Lewi D, Mathieson T, Meyer T, Pangonis D, Platt FM, Tsang L, Verburg C, Factor M, Strupp M. A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 gangliosidoses, and ataxia telangiectasia. Trials. 2021 Jan 22;22(1):84. doi: 10.1186/s13063-020-05009-3.

  PMID: 33482890 DERIVED

MeSH Terms

Conditions

Ataxia Telangiectasia

Interventions

IB1001; acetylleucine

Condition Hierarchy (Ancestors)

Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Neurologic Manifestations; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

This study was ongoing during the COVID-19 pandemic, and the conduct of this study was impacted by the COVID-19 pandemic. Additionally, it was determined by the Sponsor that a Phase III, double-blind, randomized, placebo- controlled study for A-T should be conducted to support the marketing application with IB1001 for A-T (NCT NCT06673056). Accordingly, the IB1001-203 clinical study was terminated prior to reaching the target recruitment, to prioritize the pivotal Phase III trial.

Results Point of Contact

• Title: Taylor Fields, Chief Product Development Officer
• Organization: Intrabio Ltd

tfields@intrabio.com

+44 8081

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The primary evaluation of the Clinical Impression of Change in Severity (CI-CS; Primary Endpoint) will be performed by two independent neurologists whose assessments are based on videos of patient's performance on either the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or the 8 Meter Walk Test (8MWT) taken at each visit.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be assessed during three study phases: a baseline period (with or without a study run-in), a treatment period, and a washout period.

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 30, 2018
• Study Start: January 8, 2020
• Primary Completion: February 11, 2025
• Study Completion: October 27, 2025
• Last Updated: March 25, 2026
• Results First Posted: March 25, 2026

Record last verified: 2026-03

Locations

GB (1); DE (1); US (1); ES (1)