An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome
An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome Using an "N of 1" Study Design
Unravel Biosciences, Inc.
5 participants
Mar 15, 2026
INTERVENTIONAL
Conditions
Summary
The study is an exploratory evaluation of the safety and efficacy of vorinostat in Pitt Hopkins syndrome. Each patient will be self-controlled in an adapted N-of-1 study design methodology with three treatment arms, including a 4-week placebo phase and two vorinostat dose arms, including every 8 weeks of daily dosing at a low dose of 80mg/m2/day and 8 weeks of a higher dose at 160mg/m2/day. Key objectives of the study include: * To confirm the safety and tolerability of oral vorinostat 80mg/m2/day and 160mg/ m2/day dose levels when administered to PTHS 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 PTHS
Eligibility
Inclusion Criteria9
- Subjects ≥3 years of age and ≤ 21 years of age at time of screening
- Clinical diagnosis of PTHS with documented pathologic mutation in the TCF4 gene
- At time of screening, is in a post-regression phase with no degradation of ambulation, hand function, speech or communication skills in the 4 months prior to screening
- Has been on a stable regimen of medication or non-pharmacological treatment for at least 4 weeks prior to the baseline visit
- Has had a stable pattern of seizure activity for 4 weeks before screening
- Can swallow medication or can take it by gastrostomy tube
- Can wear actigraphy data logging device on wrist or ankle
- If of childbearing potential, must agree to use a highly effective method of contraception during the study and for 3 months after the last study drug administration (i.e., abstinence from sexual activity, hormonal contraceptives associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system)
- Subjects or their legally authorized representative must be able to provide an informed consent and have sufficient language skill to complete caregiver assessments in the language in which the study assessments are provided
Exclusion Criteria16
- Has another clinically significant medical condition other than those related to their TCF4 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
- Has clinically significant abnormal vital signs at screening or baseline
- Has an abnormal ECG at screening, including clinically significant QT prolongation
- Has a clinically significant abnormal laboratory value at screening
- Liver disease or transaminase levels > 1.5 times the upper limit of the normal range as determined during screening
- Has a history of malignancy of any organ system within the past 5 years before screening
- Is participating in or has participated in another clinical trial within 30 days prior to the screening visit
- Has been treated with growth hormone, IGF-1, or insulin within 12 weeks of baseline
- Is taking anticoagulant therapy or other HDAC inhibitors
- Has had any change to their medication or non-pharmacological treatment within 4 weeks prior to the baseline visit
- Life expectancy of less than 12 months.
- Has a history of alcoholism or drug/chemical abuse within 2 years before screening.
- In the investigator's opinion, is inappropriate for this study for any reason
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Interventions
oral suspension
placebo
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07150026