Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as mavoglurant
AFQ056 · 16 trials · 15 indications
The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment.
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 modified AIMS is a scale used to assess dyskinesia. It focuses on six different parts of the body and rates abnormal movements from 0 (absence of dyskinesia to 4 (severe) (maximal score, 24). Change from baseline to Week 12 will be analyzed using the mixed effect repeated measures model (MMRM) including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
The occurrence of adverse events would be sought by non-directive questioning of the patient. Adverse events may also be detected when they are volunteered by the patient or through physical examination, laboratory test, or other assessments. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
The occurrence of adverse events (AEs) would be sought by non-directive questioning of the patient. Adverse events may also be detected when they are volunteered by the patient or through physical examination, laboratory test, or other assessments. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
Randomized patients will be up titrated to the target dose and remain on the target dose for the duration of the fixed dose treatment period. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
Patients randomized will be up titrated to the target doses at regular intervals during the up titration period. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
The occurrence of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
The occurrence and severity of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Pulse and blood pressure at each visit as indicated above. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Standard hematology with differential, aPTT, PT/INR;, clinical chemistry consists of albumin, alkaline phosphatase, amylase, total bilirubin, calcium, cholesterol, creatinine, CK, γ-GT, glucose, lipase, lactate dehydrogenase, inorganic phosphorus, magnesium, potassium, total protein, AST, ALT, sodium, triglycerides, urea and uric acid, FSH, LH, oxytocin, prolactin, TBG, TSH, and T4; urinalysis (specific gravity, protein, glucose and blood) If a patient discontinues in between these visits, these will be assessed at the time of discontinuation.
A standard 12-lead ECG will be performed. A central facility will be used for interpretation and analysis of the ECGs. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Part III of the UPDRS (items 18-31; total score 0-56), has been proven to be a reliable instrument in assessing the anti-parkinsonian effect in PD patients. This scale measures 14 items such as speech, facial expression, tremor, action or postural tremor, rigidity, finger taps, hand movement, alternating movement, leg agility, arising from a chair, posture, gait, postural stability, and bradykinesia. A higher score is indicative of worsening of symptoms. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
The occurrence of adverse events relating to the underlying movement disorder Parkinson's disease would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
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)
AUClast, AUCinf, Cmax, Tmax, T1/2, CL/F, Vz/F
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Matching tablet of placebo taken orally BID |
| AFQ056 | EXPERIMENTAL | Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days |
| 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). |
| AFQ056 150 mg | EXPERIMENTAL | Patients randomized to the AFQ056 150 mg arm will receive AFQ056 oral tablets to be titrated until reaching the target dose of 150 mg twice daily. |
| AFQ056 200 mg | EXPERIMENTAL | Patients randomized to the AFQ056 200 mg arm will receive AFQ056 oral tablets to be titrated until reaching the target dose of 200 mg twice daily. Patients will be randomized in two groups by amantadine status. * Group 1: Patients are not permitted to take amantadine within 2 weeks prior to the BL1 visit. * Group 2: Patients must be on a stable and well tolerated dose of amantadine for at least 4 weeks prior to BL1 and must maintain the stable dose of amantadine during the remainder of the study.) |
| AFQ056 100 mg | EXPERIMENTAL | - |
| 25 mg bid | EXPERIMENTAL | - |
| 50 mg bid | EXPERIMENTAL | - |
| 100 mg bid | EXPERIMENTAL | - |
| 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 |
| AFQ056 100 mg (Bid) | EXPERIMENTAL | - |
| AFQ056-10mg | EXPERIMENTAL | - |
| AFQ056-25mg | EXPERIMENTAL | - |
| AFQ056-50mg | EXPERIMENTAL | - |
| AFQ056-75mg | EXPERIMENTAL | - |
| AFQ056-100mg | EXPERIMENTAL | - |
| Active | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | - |
| 2 | PLACEBO_COMPARATOR | - |
| All Study subjects | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| AFQ056 | DRUG | 50 mg and 100 mg tablets taken orally |
| Placebo | DRUG | Matching placebo tablets taken orally BID |
| 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. |
| AFQ056 with L-dopa | DRUG | hard gelatin capsule to be taken bid for six weeks |
Inclusion Criteria: * Understand the study procedures and provide written informed consent before any assessment is performed. * Subjects diagnosed with Cocaine Use Disorder according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Ed.). * Must use cocaine through snorting (int...
AFQ056 is an investigational small molecule developed by Novartis AG for psychiatric and neurological conditions. It has been studied in Phase 2 clinical trials for cocaine use disorder, Fragile X Syndrome, and L-dopa induced dyskinesias in Parkinson's disease. It is not approved and remains in clinical development.
AFQ056 has been studied in Phase 2 trials for cocaine-related disorder, Fragile X Syndrome, and L-dopa induced dyskinesias in Parkinson's disease. Additional research has explored its use in gastroesophageal reflux disease and hepatic impairment. It is investigational and not approved for any indication.
AFQ056 is being developed by Novartis AG, which trades under the ticker NVS. Novartis has sponsored the clinical trial program evaluating AFQ056 across psychiatric and neurological indications.
AFQ056 is in Phase 2 clinical development. Five Phase 2 trials have been completed, and no active trials are currently listed. The drug is investigational and has not received FDA approval for any indication.
AFQ056 has been evaluated in five completed Phase 2 trials, including NCT03242928 in cocaine use disorder, NCT02920892 in Fragile X Syndrome, and NCT01491932 and NCT01491529 in Parkinson's disease patients with L-dopa induced dyskinesias. These trials enrolled a total of 445 participants.