Trial Outcomes & Findings for AFQ056 for Language Learning in Children With FXS (NCT NCT02920892)

NCT ID: NCT02920892

Last Updated: 2023-10-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

110 participants

Primary outcome timeframe

Baseline through Month 8

Results posted on

2023-10-10

Participant Flow

It is expected that recruitment/enrollment will occur over 18 months. Enrollment must end at the end of February 2020 due to study drug expiration at the end of August 2021.

Prior to randomization, there will be a 4-month single-blind placebo lead in after screening assessments during which subjects will have therapy treatments as usual to control for the effects of the language intervention. The placebo lead-in will also control for placebo effects which are prominent in clinical trials in FXS.

Participant milestones

Participant milestones
Measure	Placebo Lead-In Children with FXS were seen for a screening visit and if they met entry criteria, they began a single-blind 4-month placebo lead-in period prior to randomization during which they received their therapy treatments as usual, with no language intervention.	Double-Blind Placebo, Then Open-Label AFQ056 Double-Blind Placebo Period: 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 Period: 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 total duration of the OLE depended on when the subject was enrolled into the study and ranged from no open label to 8 months.	Double-Blind AFQ056, Then Open-Label AFQ056 Double-Blind Placebo Period: 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. Open-Label Period: 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 total duration of the OLE depended on when the subject was enrolled into the study and ranged from no open label to 8 months.
Placebo Lead-In Period STARTED	110	0	0
Placebo Lead-In Period COMPLETED	99	0	0
Placebo Lead-In Period NOT COMPLETED	11	0	0
Placebo-Controlled Period STARTED	0	49	50
Placebo-Controlled Period COMPLETED	0	46	43
Placebo-Controlled Period NOT COMPLETED	0	3	7
Open-Label Extension (OLE) Period STARTED	0	46	43
Open-Label Extension (OLE) Period COMPLETED	0	37	39
Open-Label Extension (OLE) Period NOT COMPLETED	0	9	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Lead-In Children with FXS were seen for a screening visit and if they met entry criteria, they began a single-blind 4-month placebo lead-in period prior to randomization during which they received their therapy treatments as usual, with no language intervention.	Double-Blind Placebo, Then Open-Label AFQ056 Double-Blind Placebo Period: 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 Period: 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 total duration of the OLE depended on when the subject was enrolled into the study and ranged from no open label to 8 months.	Double-Blind AFQ056, Then Open-Label AFQ056 Double-Blind Placebo Period: 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. Open-Label Period: 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 total duration of the OLE depended on when the subject was enrolled into the study and ranged from no open label to 8 months.
Placebo Lead-In Period Withdrawal by Subject	1	0	0
Placebo Lead-In Period Subject Ineligible	6	0	0
Placebo Lead-In Period Subject Screen Fail	4	0	0
Placebo-Controlled Period Withdrawal by Subject	0	3	5
Placebo-Controlled Period Physician Decision	0	0	1
Placebo-Controlled Period Lost to Follow-up	0	0	1
Open-Label Extension (OLE) Period Withdrawal by Subject	0	5	2
Open-Label Extension (OLE) Period Study Drug Expiration	0	4	2

Baseline Characteristics

AFQ056 for Language Learning in Children With FXS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants 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.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants 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.	Total n=99 Participants Total of all reporting groups
Age, Continuous	5.1 years STANDARD_DEVIATION 1.4 • n=5 Participants	5.3 years STANDARD_DEVIATION 1.3 • n=7 Participants	5.2 years STANDARD_DEVIATION 1.4 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	46 Participants n=7 Participants	88 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=5 Participants	42 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants	41 Participants n=7 Participants	84 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	47 participants n=5 Participants	50 participants n=7 Participants	97 participants n=5 Participants
Region of Enrollment China	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Weighted Child Intentional Communication Score	282.8 score on a scale STANDARD_DEVIATION 264.2 • n=5 Participants	304.0 score on a scale STANDARD_DEVIATION 270.2 • n=7 Participants	293.2 score on a scale STANDARD_DEVIATION 266.0 • n=5 Participants
Mullen Scales of Early Learning (MSEL) Developmental Quotient (DQ)	45.4 units on a scale STANDARD_DEVIATION 14.4 • n=5 Participants	43.9 units on a scale STANDARD_DEVIATION 16.3 • n=7 Participants	44.6 units on a scale STANDARD_DEVIATION 15.3 • n=5 Participants
Mullen Scales of Early Learning (MSEL) Expressive Language Subscore	22.5 score on a scale STANDARD_DEVIATION 10.0 • n=5 Participants	23.2 score on a scale STANDARD_DEVIATION 10.7 • n=7 Participants	22.9 score on a scale STANDARD_DEVIATION 10.3 • n=5 Participants
Vineland Adaptive Behavior Scale (Vineland-3) Composite Score	66.0 score on a scale STANDARD_DEVIATION 10.3 • n=5 Participants	64.0 score on a scale STANDARD_DEVIATION 12.2 • n=7 Participants	65.0 score on a scale STANDARD_DEVIATION 11.3 • n=5 Participants
Vineland Adaptive Behavior Scale (Vineland-3) Communication Score	61.2 score on a scale STANDARD_DEVIATION 15.4 • n=5 Participants	56.8 score on a scale STANDARD_DEVIATION 19.1 • n=7 Participants	59.0 score on a scale STANDARD_DEVIATION 17.4 • n=5 Participants
Preschool Language Scale (PLS-5) Expressive Communication Score	28.8 scores on a scale STANDARD_DEVIATION 9.9 • n=5 Participants	29.7 scores on a scale STANDARD_DEVIATION 10.7 • n=7 Participants	29.2 scores on a scale STANDARD_DEVIATION 10.3 • n=5 Participants
MacArthur-Bates Communicative Development Inventory (CDI) Number of Spoken Words	262.8 words STANDARD_DEVIATION 231.4 • n=5 Participants	305.6 words STANDARD_DEVIATION 253.3 • n=7 Participants	284.2 words STANDARD_DEVIATION 242.3 • n=5 Participants
Clinical Global Impression - Improvement: Overall Function Much/very much improved	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Clinical Global Impression - Improvement: Overall Function Minimally improved	4 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants
Clinical Global Impression - Improvement: Overall Function No change	37 Participants n=5 Participants	35 Participants n=7 Participants	72 Participants n=5 Participants
Clinical Global Impression - Improvement: Overall Function Minimally worse	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Clinical Global Impression - Improvement: Overall Function Much/very much worse	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through Month 8

Population: Comparison of WCS from baseline and from month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
Change in Weighted Child Intentional Communication Score	0.14 log10(scores on a scale) Interval 0.05 to 0.22	0.04 log10(scores on a scale) Interval -0.05 to 0.12

SECONDARY outcome

Timeframe: Baseline through Month 8

Population: Comparison of DQ from baseline and from month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

Mullen Scales of Early Learning (MSEL) Developmental Quotient (DQ) is calculated by averaging the developmental age equivalents from 4 domains of the Mullen (visual reception, fine motor, receptive language, and expressive language) to find developmental age in months, dividing by chronological age in months, then multiplying by 100. DQ can range from 1 to 70. A higher DQ indicates better performance on the MSEL. The MSEL was administered at Baseline, Month 2, and Month 8. A composite score representing the average of the estimated change scores calculated at month 2 and month 8 was recorded. A negative least squares mean indicates a net decrease in DQs over time. A more negative least squares mean indicates a larger negative change in DQs over time.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
Change in Mullen Scales of Early Learning (MSEL) Developmental Quotient (DQ)	-0.7 scores on a scale Interval -1.9 to 0.5	-2.35 scores on a scale Interval -3.55 to -1.16

SECONDARY outcome

Timeframe: Baseline through Month 8

Population: Comparison of MSEL expressive language subscore from baseline and from month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

The MSEL measures performance over 5 subscales including expressive language. The range of possible subscores for the expressive language domain is 1-50. A higher score indicates better performance / greater use of expressive language The MSEL was administered at Baseline, Month 2, and Month 8. A composite score representing the average of the estimated change scores calculated at month 2 and month 8 was recorded. A positive least squares mean indicates a net positive change in expressive language scores over time. A higher least squares mean indicates a larger change in expressive language scores over time.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
Change in Mullen Scales of Early Learning (MSEL) Expressive Language Subscore	1.99 scores on a scale Interval 1.19 to 2.79	1.32 scores on a scale Interval 0.52 to 2.11

SECONDARY outcome

Timeframe: Baseline through Month 8

Population: Comparison of Vineland-3 Composite Score from baseline and from month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

The Vineland-3 composite score is yielded from the subject's level of adaptive functioning in the domains of communication, daily living skills, socialization, and motor skills. The range of possible composite scores is 20-140 with a higher score indicating higher levels of adaptive functioning. The Vineland-3 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 positive least squares mean indicates a net increase in composite score over time. A higher least squares mean indicates a greater change in composite score over time.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
Change in Vineland Adaptive Behavior Scale (Vineland-3) Composite Score	0.68 scores on a scale Interval -0.51 to 1.88	0.39 scores on a scale Interval -0.81 to 1.6

SECONDARY outcome

Timeframe: Baseline and Month 8

Population: Comparison of Vineland-3 Communication Subscore from baseline and from month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

The communication domain of the Vineland-3 examines adaptive functioning in receptive, expressive, and written language. The range of possible subscores for the communication domain is 20-140 with a higher score indicating more advanced use of language. The Vineland-3 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 positive least squares mean indicates a net increase in communication score over time. A higher least squares mean indicates a greater change in communication score over time.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
Change in Vineland Adaptive Behavior Scale (Vineland-3) Communication Subscore	0.54 scores on a scale Interval -0.97 to 2.05	0.63 scores on a scale Interval -0.9 to 2.16

SECONDARY outcome

Timeframe: Baseline and Month 8

Population: Comparison of PLS-5 expressive communication scores from baseline and from month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

The PLS-5 is a comprehensive developmental language assessment that requires the child to point to or verbally respond to items. Raw scores for expressive language were collected from this test. It is difficult to specify an upper bound on the score, because there is no clear expectation of a limit on the number of times a child can communicate unless one sets it artificially (e.g., once per second in an 11-minute free play). The lower bound is zero for a child who produces no communication acts. The PLS-5 was administered at Baseline, Month 2, and Month 8. A composite score representing the average of the estimated change scores calculated at month 2 and month 8 was recorded. A higher least squares mean indicates a larger change in PLS-5 communication score over 8 months.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
Change in Preschool Language Scale (PLS-5) Expressive Communication Score	1.78 scores on a scale Interval 1.1 to 2.46	0.93 scores on a scale Interval 0.25 to 1.6

SECONDARY outcome

Timeframe: Month 8

Population: Number of words spoken at month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

The MacArthur-Bates CDI is a parent interview that allows tracking of a child's progress in developing words, sentences, and more complex language. The assessment consists of two parts including "Words Children Use," a 680-word vocabulary checklist in which the parent indicates those vocabulary words the child regularly produces in spoken language, and "Sentences and Grammar" an assessment of several aspects of grammar and word endings. The MacArthur-Bates CDI number of spoken words will be recorded with higher scores indicating more words used / greater language development at Month 8.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
MacArthur-Bates Communicative Development Inventory (CDI) Number of Spoken Words	319 Spoken Words Interval 0.0 to 677.0	413.5 Spoken Words Interval 0.0 to 680.0

SECONDARY outcome

Timeframe: Month 8

Population: Patients with positive change in CGI-I scores from baseline to month 8 visit (end of double-blind period) in both AFQ056 \& Language Intervention and Placebo \& Language Intervention groups.

Completion of the CGI-I requires the clinician to rate how much the study participant's illness has improved or worsened relative to a baseline state. For this study, two sets of CGI-I are administered at each applicable visit - one associated with Language/Communication and the other to Overall Function. The Overall Function CGI-I considers all areas of function including cognition, adaptive behavior, and maladaptive behavior. The CGI-I is a 7-point scale that includes the following ratings: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The CGI-I was rated at all study visits after screening. This measure shows the number of participants with positive CGI-I scores indicating perceived improvement at Month 8.

Outcome measures

Outcome measures
Measure	Placebo Comparator: Double-Blind Placebo With Language Intervention n=49 Participants Randomized to receive AFQ056-matched placebo twice per day in conjunction with the language intervention during the double-blind period.	Experimental: Double-Blind AFQ056 With Language Intervention n=50 Participants Randomized to receive AFQ056 twice per day in conjunction with the language intervention during the double-blind period. Subjects will take between 25-100 mg BID orally. Dose will depend on individual patient max tolerance.
Number of Participants With a Positive Response as Defined by Improvement in Clinical Global Impression - Improvement (CGI-I) Overall Function Scores	10 participants	8 participants

Adverse Events

Placebo Lead-In Period

Serious events: 1 serious events

Other events: 65 other events

Deaths: 0 deaths

Double-Blind Period: Placebo With Language Intervention

Serious events: 1 serious events

Other events: 44 other events

Deaths: 0 deaths

Double-Blind Period: AFQ056 With Language Intervention

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Open-Label Period: AFQ056 With Language Intervention

Serious events: 1 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Lead-In Period n=110 participants at risk Children with FXS were seen for a screening visit and if they met entry criteria, they began a single-blind 4-month placebo lead-in period prior to randomization during which they received their therapy treatments as usual, with no language intervention.	Double-Blind Period: Placebo With Language Intervention n=49 participants at risk Double-Blind Placebo Period: 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.	Double-Blind Period: AFQ056 With Language Intervention n=50 participants at risk Double-Blind Placebo Period: 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.	Open-Label Period: AFQ056 With Language Intervention n=89 participants at risk 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 total duration of the OLE depended on when the subject was enrolled into the study and ranged from no open label to 8 months. The OLE included 46 patients who were previously assigned to placebo and 43 patients who were previously assigned to AFQ056.
Infections and infestations Atypical Pneumonia	0.00% 0/110 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	2.0% 1/49 • Number of events 1 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	0.00% 0/50 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	0.00% 0/89 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.
Respiratory, thoracic and mediastinal disorders Croup Infectious	0.00% 0/110 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	0.00% 0/49 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	0.00% 0/50 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	1.1% 1/89 • Number of events 1 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.
Nervous system disorders Seizure	0.91% 1/110 • Number of events 1 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	0.00% 0/49 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	0.00% 0/50 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.	0.00% 0/89 • Participants were monitored for AEs from the time they signed the consent until the final Study visit, up to 21 months. If an AE was ongoing or discovered at a subject's final Study visit, the AE was followed until resolution, or for a minimum of 30 days, whichever comes first. Adverse event review were done at all study visits, and during dose titration reviews. Safety monitoring was based on close observation of the child by the family. Children in the proposed age range who have developmental delay with a mental age of approximately 1-5 years are not be able to spontaneously communicate all (if any) side effects. Therefore, adverse event information was collected by querying caregivers about any differences in the child's behavior or wellbeing.

Other adverse events

Additional Information

Elizabeth Berry-Kravis, MD PhD

Rush University Medical Center

Phone: 312-942-4036

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60