ClinicalTrials.gov record NCT07150026
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
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
An exploratory, proof-of-concept trial testing the oral drug vorinostat in people with Pitt Hopkins syndrome. Each participant follows an adapted 'n of 1' crossover schedule with a 4-week placebo period and two active periods (8 weeks low dose, then 8 weeks higher dose). Up to five patients will be enrolled.
What it is studying. The study is testing the safety and tolerability of two daily dose levels of oral vorinostat and measuring clinical and molecular (transcriptome/RNA) changes during treatment compared with a placebo period. Primary measurements include treatment-related adverse events, treatment discontinuations, and changes in transcriptome (RNA-seq) profiles; secondary measures include clinical scales, caregiver impressions, sleep, seizure, motor, communication and gastrointestinal symptom assessments.
What the researchers hope to learn. Confirm safety and tolerability of oral vorinostat at 80 mg/m2/day and 160 mg/m2/day in Pitt Hopkins patients; identify the nature and magnitude of any treatment-associated changes on clinical measures and in transcriptome (RNA-seq) profiles; and provide data to inform design and analysis of future clinical studies.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Vorinostat (SAHA)
- Placebo
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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 criteria
- 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
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
Unravel Biosciences, Inc. ("Unravel") proposes to develop an orally administered, once daily novel treatment for the orphan drug indication of Pitt Hopkins syndrome. Unravel has utilized its proprietary drug discovery platform to identify drugs having potential therapeutic value for neurodevelopmental disorders caused by gene mutations shown to have a cascading effect on other genes. Unravel's platform combines human gene regulatory network-based computational drug prediction with in vivo screening in a population-level diversity, CRISPR-edited, Xenopus laevis tadpole disease model. Through use of Unravel's platform, the drug vorinostat ranked highly in predictive scoring for Pitt Hopkins syndrome. In work done for Rett syndrome, another orphan CNS disease with many molecular and phenotypic similarities to Pitt Hopkins syndrome, vorinostat broadly improved both CNS and non-CNS (e.g., gastrointestinal, respiratory, inflammatory) abnormalities in a pre-clinical mouse model of Rett syndrome. Vorinostat was the first treatment to demonstrate nonclinical efficacy across multiple organ systems when dosed after the onset of symptoms, and network analysis revealed a putative therapeutic mechanism for its cross-organ normalizing effects based on its impact on acetylation metabolism and post-translational modifications of microtubules, leading to the selection of vorinostat as a target candidate for further assessment in both Rett and Pitt Hopkins syndromes. The main hypotheses informing the goals and design of the study are as follows:
- Vorinostat is safe and tolerable when dosed in typical Rett patients at dose levels up to 160mg/m2/day
- At a molecular level, vorinostat mitigates the impact of the underlying TCF4 gene mutation in PTHS patients by restoring downstream mRNA synthesis, as measured by transcriptome data
- Vorinostat provides clinical benefit to Pitt Hopkins patients by reducing frequency and severity of clinical signs/symptoms and improving patient quality of life
The study is designed as an exploratory, proof of concept trial to investigate the study hypotheses as stated above and to achieve the primary goals of the trial. The study design adapts the well-known "n of 1" crossover study methodology (Guyatt, et.al., 1990, Kravitz, et.al., 2014), where each patient serves as their own control during comparative analyses of safety and efficacy. Up to 5 patients will be enrolled in the study to explore the hypothesis that vorinostat is a safe and potentially effective treatment for Pitt Hopkins syndrome. Each patient enrolled in the study will be exposed to a 4-week placebo study phase to generate baseline data that will serve as a control as well as two active drug phases with vorinostat treatment, starting at 80mg/m2/day dosing for 8 weeks, followed by dose escalation to 160mg/m2/day for 8 weeks. The study is designed to be single-blinded, where patients and their caregivers will not be aware of their treatment assignment in an attempt to minimize bias where practically possible, especially given the subjective nature of several of the endpoints being evaluated. Investigator, study staff, and sponsor will not be blinded to study treatment assignment.
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants will follow an adapted "n-of-1" crossover schedule of about 20 weeks: a 4-week placebo period, then 8 weeks of low-dose vorinostat (80 mg/m2/day), then 8 weeks of higher-dose vorinostat (160 mg/m2/day), taken daily as an oral suspension. They will have regular safety monitoring, wear an actigraphy device, keep a caregiver seizure diary, and complete caregiver questionnaires about symptoms, communication, sleep, pain and motor behavior. Biological samples will be collected for transcriptome (RNA) analysis, and study staff will record adverse events and treatment tolerability throughout the study.
How the study is structured. Interventional 'n of 1' crossover design where each participant serves as their own control. Each patient has three treatment periods: one 4-week placebo period, one 8-week low-dose vorinostat period, and one 8-week higher-dose vorinostat period; allocation is non-randomized. The registry lists masking as double, but the detailed study description also states that patients and caregivers are blinded while investigators and study staff are not, an apparent inconsistency in the record. Up to five patients will be enrolled for this exploratory study.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- Some participants receive a placebo. How is that decided, and what happens for placebo-group participants when the study ends?
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in Colombia. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Pitt-Hopkins syndrome
Important dates
- Study start
- Mar 15, 2026
- Primary completion
- Dec 31, 2026 (estimated)
- Study completion
- Mar 15, 2027 (estimated)
- Target enrollment
- 5 participants (estimated)
- Last updated on registry
- Sep 17, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Unravel Biosciences, Inc.
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Neal I Muni, M.D., MSPH 📞 +1 857-404-8252 ✉ neal.muni@unravel.bio
Participating sites (1)
- Grupo de Investigación Clínica PECET (GIC-PECET)Recruiting
Medellín · Colombia
- Coordinadora de estudios clinicos · +57 3023575173 · liliana.lopez@pecet-colombia.org
Terms used on this page · explanations by MedicalUpdates.ai
- placebo
- A treatment that looks like the study treatment but contains no active ingredient. Some participants receive it instead of the study treatment, usually without knowing which they got.
- prior to screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- stable regimen
- A dose that has not changed for a defined period before the study starts. Studies may require this so that background treatment is relatively stable when study measurements begin.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- legally authorized representative
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- ECG
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- Life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- crossover
- Each participant receives more than one intervention, one after the other, usually with a gap (a washout) in between. Participants act as their own comparison.
- dose escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- blinded
- Who does not know which intervention a participant is receiving. It can apply to participants, the people giving the treatment, those assessing results, or those analysing the data.
- endpoints
- Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.
- sponsor
- The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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