Clinical Trial: A Placebo-controlled Study of Efficacy & Safety of 2 Trough-ranges of Everolimus as Adjunctive Therapy in Patients With Tuberous Sclerosis Complex (TSC) & Refractory Partial-onset Seizures

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Three-arm, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Two Trough-ranges of Everolimus as Adjunctive Therapy in Patients With Tuberous Scle

Brief Summary:

This study will evaluate the efficacy and safety of two trough-ranges of everolimus given as adjunctive therapy in patients with tuberous sclerosis complex (TSC) who have refractory partial-onset seizures.

The study consists of 4 phases for each patient [Baseline phase: From Screening Week -8 (V1) to randomization visit at Week 0 (V2)], Core phase, from randomization at Week 0 (V2) to Week 18 (V11)], Extension phase from Week 18 (V11) until 48 weeks after the last patient has completed the core phase, and Post Extension Phase [after the end of the Extension phase until August 31, 2017].


Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome:

  • European Medicine Agency (EMA): Response rate [ Time Frame: Baseline, Week 12 ]
    Response means at least a 50% reduction from baseline in partial-onset seizure frequency
  • Food & Drug Administration (FDA): Percentage reduction in partial onset seizure frequency [ Time Frame: Baseline, Week 12 ]
    Percentage reduction from baseline in partial onset seizure frequency during maintenance period of the core phase.


Original Primary Outcome:

  • European Medicine Agency (EMA): Response rate [ Time Frame: Baseline, Week 6 ]
    Response means at least a 50% reduction from baseline in partial-onset seizure frequency
  • European Medicine Agency (EMA): Response rate [ Time Frame: Baseline, Week 12 ]
    Response means at least a 50% reduction from baseline in partial-onset seizure frequency
  • Food & Drug Administration (FDA): Percentage reduction in partial onset seizure frequency [ Time Frame: Baseline, Week 6 ]
  • Food & Drug Administration (FDA): Percentage reduction in partial onset seizure frequency [ Time Frame: Baseline, Week 12 ]


Current Secondary Outcome:

  • Seizure free rate [ Time Frame: Baseline, Week 6, Week 18 ]
    Seizure free means a 100% reduction in partial onset-seizure frequency
  • Proportion of patients with at least a 25% reduction in partial onset seizure frequency [ Time Frame: Baseline, Week 6, Week 18 ]
  • Categorical variable of six levels of reduction from baseline in partial-onset seizure frequency [ Time Frame: Baseline, Week 6 to 18 (during maintenance of core phase) ]
    Six levels of reduction: (≤ -25% (exacerbation); > -25% to < 25% (no change); ≥ 25% to < 50%; ≥ 50% to < 75%; ≥ 75% to < 100%; 100% (seizure-freedom)
  • Frequency of seizure free days [ Time Frame: Week 6, Week 18 ]
  • Treatment duration [ Time Frame: Week 0 (randomization), Week 18 ]
    Time from randomization until treatment discontinuation in the Core phase
  • Overall Quality of Life global scores [ Time Frame: Baseline, Week 18, and End of Treatment (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
    Taken from the 3 age-specific questionnaires
  • Sub-test scores for neurocognitive, neurodevelopmental, and neurobehavioral tests [ Time Frame: Baseline, 18 weeks (End of Core), Every 6 months during Extension, End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
    Changes in the Vineland Adaptive Behavior Scales-II and the Wechsler Non-Verbal Scale of Ability
  • Percentage reduction in seizure frequency/frequency of selected adverse events [ Time Frame: Baseline, end of study (if patient completes range from 74 to 142 weeks) ]
  • Pre-dose concentrations of anti-epileptic drugs (AEDs) alone and post-baseline (AEDs plus everolimus) [ Time Frame: Baseline, Week 3 ]
  • 50% response rate from Baseline by time interval over the extension phase [ Time Frame: Week 18 (start of Extension), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Seizure free days in partial onsent seizure by time interval over the extension phase [ Time Frame: Week 18 (Start of Extension), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of adverse events [ Time Frame: Baseline, End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of abnormal laboratory values [ Time Frame: Baseline, End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of Columbia Suicide Severity Rating Scale (C-SSRS) outcomes [ Time Frame: Week 8 (screening), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of serious adverve events (SAEs) referring to a positive suicidal evaluation [ Time Frame: Week 8 (Screening), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]


Original Secondary Outcome:

  • Seizure free rate [ Time Frame: Baseline, Week 6, Week 18 ]
    Seizure free means a 100% reduction in partial onset-seizure frequency
  • Proportion of patients with at least a 25% reduction in partial onset seizure frequency [ Time Frame: Baseline, Week 6, Week 18 ]
  • Categorical variable of six levels of reduction from baseline in partial-onset seizure frequency [ Time Frame: Baseline, Week 6 to 18 (during maintenance of core phase) ]
    Six levels of reduction: (≤ -25% (exacerbation); > -25% to < 25% (no change); ≥ 25% to < 50%; ≥ 50% to < 75%; ≥ 75% to < 100%; 100% (seizure-freedom)
  • Frequency of seizure free days [ Time Frame: Week 6, Week 18 ]
  • Treatment duration [ Time Frame: Week 0 (randomization), Week 18 ]
    Time from randomization until treatment discontinuation in the Core phase
  • Overall Quality of Life global scores [ Time Frame: Baseline, Week 18, and End of Treatment (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
    Taken from the 3 age-specific questionnaires
  • Sub-test scores for neurocognitive, neurodevelopmental, and neurobehavioral tests [ Time Frame: Baseline, 18 weeks (End of Core), Every 6 months during Extension, End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
    Changes in the Vinela nd Adaptive Behavior Scales-II and the Wechsler Non-Verbal Scale of Ability
  • Percentage reduction in seizure frequency/frequency of selected adverse events [ Time Frame: Baseline, end of study (if patient completes range from 74 to 142 weeks) ]
  • Pre-dose concentrations of anti-epileptic drugs (AEDs) alone and post-baseline (AEDs plus everolimus) [ Time Frame: Baseline, Week 5 ]
  • 50% response rate from Baseline by time interval over the extension phase [ Time Frame: Week 18 (start of Extension), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Seizure free days in partial onsent seizure by time interval over the extension phase [ Time Frame: Week 18 (Start of Extension), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of adverse events [ Time Frame: Baseline, End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of abnormal laboratory values [ Time Frame: Baseline, End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of Columbia Suicide Severity Rating Scale (C-SSRS) outcomes [ Time Frame: Week 8 (screening), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]
  • Frequency of serious adverve events (SAEs) referring to a positive suicidal evaluation [ Time Frame: Week 8 (Screening), End of Treatment Extension (time when patient completes or leaves study. Range from 74 to 142 weeks) ]


Information By: Novartis

Dates:
Date Received: October 9, 2012
Date Started: April 29, 2013
Date Completion: October 30, 2017
Last Updated: May 15, 2017
Last Verified: May 2017