Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02920892 | AFQ056 for Language Learning in Children With FXS | PHASE2 | COMPLETED | 110 | — | — | Aug 17, 2017 | May 17, 2022 | Oct 10, 2023 | 14 | United States |
| NCT01357239 | Safety and Efficacy of AFQ056 in Adolescent Patients With Fragile X Syndrome | PHASE2 | COMPLETED | 139 | — | — | May 1, 2011 | Jan 1, 2014 | May 12, 2015 | 38 | United States, Australia +14 |
| NCT01253629 | Safety and Efficacy of AFQ056 in Adult Patients With Fragile X Syndrome | PHASE2 | COMPLETED | 175 | — | — | Nov 1, 2010 | Aug 1, 2013 | Dec 23, 2020 | 31 | United States, Australia +8 |
| NCT01482143 | Clinical Study to Assess the Pharmacokinetics, Safety and Tolerability of Single and Multiple Oral Doses of AFQ056 in Children With Fragile X Syndrome (FXS) | PHASE1 | COMPLETED | 21 | — | — | Mar 1, 2012 | Oct 1, 2013 | Dec 8, 2020 | 4 | United States, Spain |
The Weighted Child Intentional Communication Score is derived from a 22 minute semi-structured examiner/child play session. Structured and unstructured component scores are found by multiplying each intentional communication act by the following weights: nonverbal = 1; single symbol = 2; and multiple symbols = 3. The two scores are summed together to obtain the total. Higher scores indicate more child-initiated communication. There is no maximum score. The scale was administered at Baseline, Month 2, Month 4, Month 6, and Month 8. A composite score representing the average of the estimated change scores calculated at months 2, 4, 6, and 8 was recorded. A higher least squares mean value indicates a greater increase in WCS score from baseline.
The Aberrant Behavior Checklist-Community edition (ABC-C) is a 58-item, caregiver-rated symptom checklist for assessing problem behaviors of children and adults with mental retardation at home, in residential facilities, and work training centers. The assessment was done by attributing to each item a score from 0 ("not at all a problem") to 3 ("problem is severe in degree") and the total score ranks from 0 to 174. The data collected from the full, 58-item ABC-C were analyzed according to the modified FXS ABC-C algorithm (ABC-CFX) for which 55 items and six subscales (irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity, inappropriate speech and social avoidance) plus the total score were considered, and for which the total score ranks from 0 to 165. Stratum I included patients whose Fragile X Mental Retardation 1 (FMR1) gene was fully methylated
The ABC-C is a 58-item questionnaire that should have been completed as much as possible by the same rater. It is comprised of five subscales (irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity and inappropriate speech) plus the total score which ranks from 0 to 174 in patients who were fully methylated (FM)
| Arm | Type | Description |
|---|---|---|
| Double-Blind AFQ056 with language intervention | EXPERIMENTAL | After a 4-month single-blind placebo lead-in period, subjects with FXS were randomized to receive AFQ056 suspension by mouth twice per day in an 8 month double-blind treatment period. During the double-blind treatment period, subjects in the AFQ056 treatment group began with a dose of 25 mg AFQ056 twice per day and titrated to their maximum tolerated dose over the course of 7 weeks. After 7 weeks the dose was fixed, and at the 2 month visit, the intensive language intervention was initiated. Subjects continued the language intervention while remaining on a stable dose of AFQ056 (ranging from 12.5 mg BID to 100 mg BID), for the next 6 months. Safety and efficacy assessments were performed throughout. |
| Double-Blind Placebo with language intervention | PLACEBO_COMPARATOR | After a 4-month single-blind placebo lead-in period, subjects with FXS were randomized to receive a placebo suspension by mouth twice per day in an 8 month double-blind treatment period. During the double-blind treatment period, dose titration to maximum tolerated dose of matching placebo occurred over 7 weeks. After 7 weeks, the dose was fixed, and at the 2 month visit, the intensive language intervention was initiated. Subjects continued the language intervention while remaining on placebo for the next 6 months. Safety and efficacy assessments were performed throughout. |
| Open-Label AFQ056 with language intervention | EXPERIMENTAL | After 8 months of treatment in the placebo-controlled phase, all subjects had assessments completed and were given the opportunity to enter the open-label extension (OLE) in which all subjects received AFQ056. The OLE began with 2 months of flexible dose titration to each subject's maximum tolerated dose followed by a period of stable treatment. Subjects also continued the language intervention through the extension phase. The duration of the stable treatment depended on when the subject was enrolled into the study. Those enrolled prior to June 15-30, 2019 received a 6-month period of stable treatment. Those enrolled after June 15, 2019 had their period of stable treatment shortened on a sliding scale, such that their treatment including weaning, if necessary, ended before August 31, 2021 (study drug expiration). |
| 25 mg bid | EXPERIMENTAL | - |
| 50 mg bid | EXPERIMENTAL | - |
| 100 mg bid | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| 25 mg bid AFQ056 | EXPERIMENTAL | 1 capsule of 25 mg and 1 capsule of placebo per intake |
| 50 mg bid AFQ056 | EXPERIMENTAL | 2 capsules of 25 mg per intake |
| 100 mg bid AFQ056 | EXPERIMENTAL | 1 capsule of 100 mg and 1 capsule of placebo per intake |
| All Study subjects | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| AFQ056 | DRUG | 12.5 mg - 100 mg oral suspension (liquid) |
| Placebo | DRUG | Placebo oral suspension (liquid) |
| Language Intervention | OTHER | All subjects will begin an intensive language intervention 2 months after starting treatment with AFQ056 or placebo and will continue the intervention through the end of the study. The language intervention will be administered by a trained language specialist through a combination of in clinic visits and at home synchronous video conferencing sessions. The intervention will subsequently be delivered to the parent by a speech-language clinician through weekly clinician coaching, homework, and feedback sessions. The language intervention is designed to help parents learn and use verbally responsive interactional strategies more frequently and effectively throughout the course of their daily interactions with their children. |
Inclusion Criteria 1. Age 32 months to 6 years inclusive at Screening (visit 1). 2. Has an FMR1 full mutation. \*\*Note Presence of mosaicism is allowed 3. DQ\<75 calculated from the Mullen Scales of Early Learning at time of screening. 4. Parent or legal guardian is available and able to commu...