The RETT REVOLUTION trial is a placebo-controlled, single-blinded, exploratory study with patients serving as their own control ("N of 1" trial design) where the safety and efficacy of vorinostat in the treatment of Rett syndrome will be evaluated. Each patient will be self-controlled in an adapted N-of-1 study design methodology by using a 4-week placebo baseline. Vorinostat dose escalation will occur every 8 weeks of daily dosing: placebo, 80mg/m2/day, 160mg/m2/day.
Key study objectives will include:
* To confirm the safety and tolerability of oral vorinostat 80mg/m2/day and 160mg/ m2/day dose levels when administered to typical Rett patients * To identify the nature and magnitude of treatment response to vorinostat, as measured by changes in clinical and laboratory parameters indicative of trend towards benefit, as well as changes in mRNA expression (transcriptome response) * Provide a data-driven justification for future study design and statistical analysis plan for subsequent clinical studies assessing safety and efficacy of vorinostat in Rett syndrome
Female subjects ≥6 years of age and ≤ 21 years of age at time of screening
Has typical Rett Syndrome (RTT), based on diagnostic criteria for RTT described in Neul, et.al., 2010
Has documented, disease causing mutation in the MeCP2 gene
At time of screening, is in the post-regression phase with no degradation of ambulation, hand function, speech or communication skills in the 4 months prior to screening
Has another clinically significant medical condition other than those related to MeCP2 mutation (e.g. diabetes mellitus, cardiovascular disease, renal disease, respiratory disease, hematological abnormalities, malignancy)
Has major surgery planned during the study period
Pregnant or nursing women
Has a history of brain injury, stroke, other cerebrovascular disease or hypoxic-ischemic encephalopathy