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NCT02920892: FX-LEARN

AFQ056 for Language Learning in Children With FXS

Completed Phase 2 Results posted Last updated 10 October 2023
What this trial tests

Phase 2 trial testing AFQ056 in Fragile X Syndrome in 110 participants. Completed in 17 May 2022.

Timeline
17 August 2017
Primary endpoint
17 May 2022
17 May 2022

Quick facts

Lead sponsorElizabeth Berry-Kravis
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment110
Start date17 August 2017
Primary completion17 May 2022
Estimated completion17 May 2022
Sites14 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Elizabeth Berry-Kravis — full company profile →

Who can join

Adults 32 Months to 6, any sex, with Fragile X Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Weighted Child Intentional Communication Score Primary · Baseline through Month 8

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 ch

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention0.140.05 – 0.22
Experimental: Double-Blind AFQ056 With Language Intervention0.04-0.05 – 0.12
Change in Mullen Scales of Early Learning (MSEL) Developmental Quotient (DQ) Secondary · Baseline through Month 8

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.

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention-0.7-1.90 – 0.50
Experimental: Double-Blind AFQ056 With Language Intervention-2.35-3.55 – -1.16
Change in Mullen Scales of Early Learning (MSEL) Expressive Language Subscore Secondary · Baseline through Month 8

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 s

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention1.991.19 – 2.79
Experimental: Double-Blind AFQ056 With Language Intervention1.320.52 – 2.11
Change in Vineland Adaptive Behavior Scale (Vineland-3) Composite Score Secondary · Baseline through Month 8

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

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention0.68-0.51 – 1.88
Experimental: Double-Blind AFQ056 With Language Intervention0.39-0.81 – 1.60
Change in Vineland Adaptive Behavior Scale (Vineland-3) Communication Subscore Secondary · Baseline and Month 8

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

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention0.54-0.97 – 2.05
Experimental: Double-Blind AFQ056 With Language Intervention0.63-0.90 – 2.16
Change in Preschool Language Scale (PLS-5) Expressive Communication Score Secondary · Baseline and Month 8

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

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention1.781.10 – 2.46
Experimental: Double-Blind AFQ056 With Language Intervention0.930.25 – 1.60
MacArthur-Bates Communicative Development Inventory (CDI) Number of Spoken Words Secondary · Month 8

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.

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention3190 – 677
Experimental: Double-Blind AFQ056 With Language Intervention413.50 – 680
Number of Participants With a Positive Response as Defined by Improvement in Clinical Global Impression - Improvement (CGI-I) Overall Function Scores Secondary · Month 8

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,

GroupValue95% CI
Placebo Comparator: Double-Blind Placebo With Language Intervention10
Experimental: Double-Blind AFQ056 With Language Intervention8

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Lead-In Period
Serious: 1/110 (1%)
Deaths: 0/110
Double-Blind Period: Placebo With Language Intervention
Serious: 1/49 (2%)
Deaths: 0/49
Double-Blind Period: AFQ056 With Language Intervention
Serious: 0/50 (0%)
Deaths: 0/50
Open-Label Period: AFQ056 With Language Intervention
Serious: 1/89 (1%)
Deaths: 0/89

Serious adverse events (3 terms)

ReactionSystemPlacebo Lead-In PeriodDouble-Blind Period: Place…Double-Blind Period: AFQ05…Open-Label Period: AFQ056 …
Atypical PneumoniaInfections and infestations
Croup InfectiousRespiratory, thoracic and mediastinal disorders
SeizureNervous system disorders
Other adverse events (18 terms — click to expand)

ReactionSystemPlacebo Lead-In PeriodDouble-Blind Period: Place…Double-Blind Period: AFQ05…Open-Label Period: AFQ056 …
Upper Respiratory Tract InfectionInfections and infestations
Psychomotor HyperactivityNervous system disorders
InsomniaPsychiatric disorders
irritabilityPsychiatric disorders
VomitingGastrointestinal disorders
GastroenteritisInfections and infestations
DiarrheaGastrointestinal disorders
AnxietyPsychiatric disorders
Otitis MediaInfections and infestations
AgitationPsychiatric disorders
AggressionPsychiatric disorders
Attention Deficit Hyperactivity DisorderPsychiatric disorders
Sleep DisorderPsychiatric disorders
PyrexiaGeneral disorders
Sensory Processing DisorderNervous system disorders
PerseverationPsychiatric disorders
Pharyngitis StreptococcalInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Atypical Pneumonia, Croup Infectious, Seizure.

Data from ClinicalTrials.gov NCT02920892 adverse events section.

Sponsor's own description

The purpose of this clinical trial is to investigate the impact of AFQ056 on language learning in 3-6 year old children with Fragile X Syndrome (FXS).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.
    Xie X, Yu T, Li X, Zhang N, et al · · 2023 · cited 246× · PMID 37669923 · DOI 10.1038/s41392-023-01589-z
  2. Developmental studies in fragile X syndrome.
    Razak KA, Dominick KC, Erickson CA. · · 2020 · cited 59× · PMID 32359368 · DOI 10.1186/s11689-020-09310-9
  3. New Targeted Treatments for Fragile X Syndrome.
    Protic D, Salcedo-Arellano MJ, Dy JB, Potter LA, et al · · 2019 · cited 41× · PMID 31241016 · DOI 10.2174/1573396315666190625110748
  4. Best Practices in Fragile X Syndrome Treatment Development.
    Erickson CA, Kaufmann WE, Budimirovic DB, Lachiewicz A, et al · · 2018 · cited 38× · PMID 30558274 · DOI 10.3390/brainsci8120224
  5. Clinical Development of Targeted Fragile X Syndrome Treatments: An Industry Perspective.
    Lee AW, Ventola P, Budimirovic D, Berry-Kravis E, et al · · 2018 · cited 30× · PMID 30563047 · DOI 10.3390/brainsci8120214
  6. Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?
    Budgett RF, Bakker G, Sergeev E, Bennett KA, et al · · 2022 · cited 24× · PMID 35645791 · DOI 10.3389/fphar.2022.893422
  7. Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments.
    Salcedo-Arellano MJ, Cabal-Herrera AM, Punatar RH, Clark CJ, et al · · 2021 · cited 23× · PMID 33215285 · DOI 10.1007/s13311-020-00968-6
  8. Effects of AFQ056 on language learning in fragile X syndrome.
    Berry-Kravis E, Abbeduto L, Hagerman R, Coffey CS, et al · · 2023 · cited 11× · PMID 37651202 · DOI 10.1172/jci171723

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