Overview
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.
Description
The primary purpose of the study is to evaluate the safety and efficacy of N-Acetyl-L-Leucine (IB1001) in the treatment of A-T investigating the efficacy in terms of improving symptoms, functioning, and quality of life against the defined endpoints in patients with A-T.
Patients will be assessed during three study phases: a baseline period, a 6-week treatment period, and a 6-week post-treatment washout period. If within 6 weeks prior to the initial screening visit, a patient has received any of the prohibited medications defined in the eligibility criteria (irrespective of the preceding treatment duration) a wash-out study-run in of 6 weeks is required prior to the first baseline assessment.
All patients will receive the study drug during this study.
For each individual patient, the study lasts for approximately 3.5 - 4 months during which there are 6 study visits to the study site.
This Extension Phase allows patients who have completed the Parent Study to, at the discretion of the Principal Investigator (PI), continue treatment with N-Acetyl-L-Leucine (IB1001). Patients will receive treatment with IB1001 for two one-year treatment periods, separated by a 6-week washout. All patients will receive the study drug during the treatment period. For each individual patient, the Extension Phase lasts for approximately 25.5 months, during which there are 6 visits to the study site.
Eligibility
Inclusion Criteria
Individuals who meet all of the following criteria are eligible to participate in the
study:
1. Written informed consent signed by the patient and/or their legal representative/
parent
2. Male or female aged ≥6 years with a confirmed diagnosis of A-T 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 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:
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 must have undergone one of the following
sterilization procedures at least 6 months prior to the first dose:
1. hysteroscopic sterilization;
2. bilateral tubal ligation or 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.
5. Non-vasectomized male patient agrees to use a condom with spermicide or abstain from
sexual intercourse during the study 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. If male, the patient agrees not to donate sperm from the first dose until 90 days
after dosing.
7. Patients must fall within:
a) A SARA score of 5 ≤ X ≤ 33 points (out of 40) AND i. Within the 2-7 range (out of
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 A-T, including those on the prohibited medication list. Non-prohibited
medications/therapies (e.g. concomitant speech 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 6
weeks 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).
Exclusion Criteria
Individuals who meet any of the following criteria are not eligible to participate in the
study:
1. Asymptomatic patients
2. Patient has clinical features of A-T, but a completely negative result on a previous
genetic test for A-T.
3. Patients who have any of the following:
1. Chronic diarrhea;
2. Unexplained visual loss;
3. Malignancies;
4. Insulin-dependent diabetes mellitus.
5. Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or
derivatives.
6. History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose,
sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan,
dimethicone, methylparaben, and potassium sorbate).
4. 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.
5. 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.
6. Known clinically-significant (at the discretion of the investigator) laboratories in
hematology, coagulation, clinical chemistry, or urinalysis, including, but not limited
to:
1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper
limit of normal (ULN);
2. Total bilirubin >1.5x ULN, unless Gilbert's syndrome is present in which case
total bilirubin >2x ULN.
7. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.
8. Current or planned pregnancy or women who are breastfeeding.
9. 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.
10. 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.
11. Patients unwilling and/or not able to undergo a 6-week washout period from any of the
following prohibited medication prior to Visit 1 (Baseline 1) and remain without
prohibited medication through Visit 6.
1. Aminopyridines (including sustained-release form);
2. N-Acetyl-DL-Leucine (e.g. Tanganil®);
3. N-Acetyl-L-Leucine (prohibited if not provided as IMP);
4. Riluzole;
5. Gabapentin;
6. Varenicline;
7. Chlorzoxazone;
8. Sulfasalazine;
9. Rosuvastatin.