IB1001-203
Research type
Research Study
Full title
Effects of N-Acetyl-L-Leucine on Ataxia-Telangiectasia (A-T): A multinational, multicenter, open-label, rater-blinded Phase II study.
IRAS ID
260363
Contact name
Anke Hensiek
Contact email
Sponsor organisation
IntraBio Ltd.
Eudract number
2018-004407-39
ISRCTN Number
ISRCTN99999999
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
not applicable, Not applicable
Duration of Study in the UK
0 years, 9 months, 18 days
Research summary
SUMMARY OF RESEARCH
The primary purpose of the study is to evaluate the safety and efficacy of N-Acetyl-L-Leucine (IB1001) in the treatment of Ataxia-Telangiectasia (A-T) and investigating the efficacy in terms of improving symptoms, functioning, and quality of life against the defined endpoints in patients with Ataxia-Telangiectasia (A-T).
A-T is a rare, devastating, autosomal-recessive cerebellar ataxia that causes progressive degeneration to the cerebellum, central nervous system (CNS), and immune system, resulting in cognitive and physical decline and premature death.
Patients with neurological onset early in life have more severe symptoms, deteriorate faster, and die sooner.
A-T is estimated to affect 1:40,000 to 1:100,000 live births. No medication has been proven effective for the treatment of inherited cerebellar ataxias, like A-T and there are no authorized treatments approved for A-T. Therefore, there is a strong need for the development of novel and more effective therapies to treat these intractable diseases.SUMMARY OF RESULTS
The study, "Effects of N-Acetyl-L-Leucine on Ataxia-Telangiectasia (A-T)): A multinational, multicenter, open-label, rater-blinded Phase II study, was funded by IntraBio Ltd." The study was conducted at 4 multinational research hospitals in Europe, the UK, and the US.
The study aimed to see if the drug N-Acetyl-L-Leucine (IB1001) could help treat symptoms of Ataxia-Telangiectasia (A-T). Currently, there are no approved treatments for A-T, which are serious and debilitating. Therefore, there is a need for new treatments to help A-T patients' symptoms and improve their everyday functioning and quality of life. An extension phase to the study aimed to investigate the long-term safety and efficacy of IB1001 for A-T.
In total, 17 patients with A-T participated in the study between 30-Jan-2020 and 11-Feb-2025. In the "parent study", patients received open-label treatment with IB1001 for approximately 6 weeks and then stopped taking IB1001 for 6 weeks (a "post-treatment washout"). In the open-label extension phase, patients received treatment with IB1001 for approximately 2-years. There was a 6-week washout period between treatment year 1 and year 2. The IB1001-203 clinical study was terminated prior to reaching the target recruitment. Initial recruitment for the study was substantially delayed by the COVID-19 pandemic, which significantly limited the ability to enroll subjects or for subjects to attend clinical study visits. It was later 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. Therefore, the Sponsor decided to prioritize recruitment to this Phase III study (IB1001-303, "Effects of N-Acetyl-L-Leucine on Ataxia-Telangiectasia (A-T): A Phase III, randomized, placebo-controlled, double-blind, crossover study," NCT06673056). Accordingly, an abbreviated clinical study report (CSR) is presented for this IB1001-203 study.
The primary Clinical Impression of Change in Severity endpoint was assessed by blinded, independent raters. The mean change during the treatment period indicated an improvement in the patients' condition at the end of the treatment period, while the mean CI-CS during the washout period (Visit 6 versus Visit 4) showed no change. After 6 weeks of treatment with IB1001, there was improvement on the secondary Scale for the Assessment and Rating of Ataxia and Investigators, Caregivers, and Patients Clinical Global Impression of Change, indicating an improvement in symptoms and functioning; When patients stopped taking IB1001, after 6-weeks, there was a deterioration in neurological signs, symptoms, functioning, and quality of life, as the benefits of treatment were lost. In the extension phase, IB1001 met its primary SARA endpoint, showing a statistically significant, clinically meaningful slowing of disease progression and a neuroprotective effect.During the parent study, 2 study drug-related adverse events were reported by 2 patients: abdominal pain (reported by 1 patient) and muscle spasms (reported by 1 patient). None of the study drug-related TEAEs was reported by more than one patient. The events were mild and transient. In the Extension Phase, 5 study drug-related adverse events were reported by 4 patients: diarrhoea (reported by 2 patients), and muscle spasms (reported by 1 patient) The events were transient.
In total, the study indicated IB1001 improves symptoms, functioning, and quality of life after 6-week treatment and also has a disease-modifying, neuroprotective effect when administered long-term. IB1001 was observed to be very safe and well-tolerated.
The positive findings from this study are supportive of the initiation of the Phase III study with A-T, designed to support a marketing authorisation application with IB1001 for the treatment of A-T.
To learn more about the study, please see ClinicalTrial.Gov (https://clinicaltrials.gov/study/NCT03759678?cond=Ataxia%20Telangiectasia&page=3&rank=29), where the findings will be submitted. The study protocol has been peer-reviewed and submitted to clincal trial gov. (https://pubmed.ncbi.nlm.nih.gov/33482890/), To learn more about the Phase III study, please see ClinicalTrial.Gov (https://clinicaltrials.gov/study/NCT06673056?cond=Ataxia%20Telangiectasia&rank=4).
REC name
HSC REC A
REC reference
19/NI/0162
Date of REC Opinion
18 Sep 2019
REC opinion
Further Information Favourable Opinion