Fragile X Syndrome
Conditions
Keywords
Fragile X Syndrome, Fra(X) Syndrome, FRAXA Syndrome
Brief summary
This study is a multisite, randomized, double-blind, placebo-controlled, phase 2 study of MG01CI (low dose and high dose once daily) for 6 weeks compared with placebo in a 1:1 ratio of 60 adolescent and adult subjects with Fragile X Syndrome (FXS). Following Screening, subjects will be randomized to MG01CI or matching placebo at Baseline (Day 0) and the 6 week Double-blind Treatment Period will begin on Day 1. The first 4 weeks of the treatment period will be a dose-optimization period, All subjects will start with two daily tablets: low dose metadoxine or matching blinded placebo. At weekly visits/phone assessments, the investigator will evaluate the dose based upon the investigator's assessment of safety and tolerability. If the subject demonstrates safety or tolerability concerns with the low dose after 1 or 2 weeks of treatment, then the subject will be discontinued. If there are no concerns about safety and tolerability after 2 weeks of treatment, then the dose will be increased to high dose or placebo. If at the high dose there are concerns about safety and tolerability, then the dose will be either kept the same or reduced to low dose for the remainder of the treatment period. There will be a 2-week Follow-up Period after the last dose of study treatment or early termination.
Detailed description
This study is a multisite, randomized, double-blind, placebo-controlled, phase 2 study of MG01CI (low and high doses of metadoxine once daily) for 6 weeks compared with placebo in a 1:1 ratio of 60 adolescent and adult subjects with FXS. Following Screening, subjects will be randomized to MG01CI or matching placebo at Baseline (Day 0) and the 6 week Double-blind Treatment Period will begin on Day 1. The first 4 weeks of the treatment period will be a dose-optimization period, during which the subject's dose of MG01CI or placebo will be optimized. Investigators and subjects will be blinded with regard to whether the subject is taking active drug or placebo. Subjects will be blinded to anticipated dose (low vs high dose), while Investigators will not be blinded to anticipated dose, low dose vs high dose. Every two weeks subjects will receive 2-week supply treatment. A phone follow-up assessment of safety and tolerability will occur during titration after 1 and 3 weeks of treatment; if the investigator has any significant concerns regarding safety and tolerability, the subject will be assessed at the site at an unscheduled visit. All subjects will be assessed at the site after 2 weeks and 4 weeks of treatment. All subjects will start with either low dose or matching blinded placebo (2 tablets daily). At weekly visits/phone assessments, the investigator will evaluate the dose based upon the investigator's assessment of safety and tolerability. If the subject demonstrates safety or tolerability concerns with the low dose after 1 or 2 weeks of treatment, then the subject will be discontinued. If there are no concerns about safety and tolerability after 2 weeks of treatment, then the dose will be increased to 2 tablets of either high dose of active treatment or placebo. If at high dose there are concerns about safety and tolerability, then the dose will be either kept the same or reduced to low dose for the remainder of the treatment period. The last 2 weeks of the treatment period will be a dose-maintenance period. During the dose-maintenance period, the subject will maintain his or her optimal dose as determined at the end of the dose-optimization period. A phone follow-up assessment of safety and tolerability will occur after 5 weeks of treatment (after 1 week of dose maintenance). If the investigator has any significant concerns regarding safety and tolerability, the subject will be assessed at the site at an unscheduled visit. The subject will be assessed at the site after 6 weeks of treatment (after 2 weeks of dose maintenance). There will be a 2-week Follow-up Period after the last dose of study treatment or early termination.
Interventions
DRUGMG01CI extended-release tablet
Metadoxine, MG01CI extended-release tablet taken for 6 weeks treatment. Starting with a dose of 700 mg for 2 weeks followed by a 2 weeks of 1400 mg and then 2 weeks of 700 mg or 1400 mg.
Sponsors
Alcobra Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
15 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is a man or a non-pregnant, non-lactating woman aged 15 to 55 years, inclusive, at the Randomization Visit. 2. Subject has Fragile X Syndrome with a molecular genetic confirmation of the full Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repetitions). 3. Subject has a score of 12 or greater on the inattentive subscale of the ADHD RS IV (as rated by the investigator in a clinical interview of the parent/legal authorized guardian/consistent caregiver). 4. Current treatment with no more than 3 prescribed psychotropic medications. Anti epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications. 1. Permitted concomitant psychotropic medications (except anti-epileptic medications and stimulants; see 4b and 4d) must be at a stable dose and dosing regimen for at least 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication. 2. Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication. 3. Subjects with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months preceding Screening, or must be seizure-free for 3 years if not currently receiving anti-epileptics. 4. Stimulant medications must be at a stable dose and dosing regimen for 12 weeks prior to Screening and must remain stable during the period between Screening and the end of the treatment period (Week 6/early termination), unless the subject is washing out; see Exclusion Criterion 4. 5. Behavioral treatments (excluding psychotherapy; see
Exclusion criteria
) must be stable for 4 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication. 6. Subject has a parent, legal authorized guardian or consistent caregiver who interacts with the subject for at least 10 hours per week and is able to provide weekly rating forms of the subject's behavior. 7. Male and Female subjects of childbearing potential must agree to use an effective contraceptive throughout the study (eg, oral contraceptives or Norplant®; a reliable double barrier method of birth control \[diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam\]; intrauterine devices; vasectomy; or abstinence) and for at least a month after the study, and females must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Females of childbearing potential are defined as women who are between menarche and 2 years post-menopause and who are not surgically sterilized. Male and female subjects who are not sexually active, and who agree to be abstinent throughout the study, will not be required to use birth control. 8. Subject and caregiver are able to attend the clinic regularly and reliably. 9. Subject is able to swallow tablets and capsules. 10. For subjects who are not their own legal guardian, subject's parent/legal authorized guardian is able to understand, read, write, and speak English fluently to complete the study-related materials (or Hebrew for Israeli subjects). 11. For subjects who are not their own legal guardian, subject's parent/legal authorized guardian is able to understand and sign an informed consent form to participate in the study. 12. If subject is his/her own legal guardian, he/she can understand and sign informed consent to participate in the study. 13. If subject is not their own legal guardian, the subject provides assent for participation in the study, if the subject has the cognitive ability to provide assent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of efficacy of MG01CI by Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale (ADHD RS-IV) | 6 weeks | To evaluate the efficacy of MG01CI (Metadoxine Extended-release) once daily compared with placebo in the treatment of symptoms of FXS in adults and adolescents as measured by the inattentive subscale of the Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale (ADHD RS-IV) (as rated by the investigator in a clinical interview of the parent/legal authorized guardian/consistent caregiver). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of efficacy of MG01C as measured by total score on the ADHD RS-IV. | 6 weeks | To evaluate the efficacy of MG01CI (Metadoxine Extended-release) once daily compared with placebo in the treatment of symptoms of FXS in adults and adolescents as measured by the total score on the ADHD RS-IV. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of safety by AE's count | 6 weeks | To evaluate the safety, and tolerability of treatment with MG01CI once daily on the adverse events (AEs); |
| Evaluation of safety by AE's vital sign measurements | 6 weeks | — |
| Safety evaluation by lab tests (hematology, chemistry, and urinalysis) | 6 weeks | — |
| Evaluation of safety by physical and neurological examinations | 6 weeks | — |
Countries
Israel, United States
Outcome results
None listed