Testing vorinostat for safety and potential benefit 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
This trial will try daily oral vorinostat at two dose levels and placebo to see if it is safe and helps children and young adults (ages 3–21) with Pitt Hopkins syndrome.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 5 (estimated) |
| Ages | 3 Years to 21 Years |
| Sex | All |
| Sponsor | Unravel Biosciences, Inc. Industry-sponsored |
| Locations | 1 site (Medellín) |
| Trial ID | NCT07150026 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1, adapted N-of-1 interventional design where each participant serves as their own control across three treatment periods: one 4-week placebo period and two 8-week vorinostat periods at low (80 mg/m2/day) and high (160 mg/m2/day) doses. The study focuses on safety and tolerability while also measuring clinical signs, laboratory markers, and transcriptome changes to identify trends toward benefit. Vorinostat was nominated by a computational and in vivo screening platform and showed nonclinical efficacy in related neurodevelopmental models, providing the rationale for this trial. Results will be used to guide dose selection and statistical planning for future clinical studies in Pitt Hopkins syndrome.
Who should consider this trial
Good fit: Children and young adults aged 3–21 with a confirmed pathogenic TCF4 mutation, in a post‑regression stable phase, able to take oral or gastrostomy medication, and on stable medications and seizure control are ideal candidates.
Not a fit: Those under 3 or over 21 years, with recent clinical regression, unstable seizures, inability to comply with dosing or actigraphy, or who are pregnant are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, vorinostat could become an oral treatment that improves neurological and systemic symptoms in Pitt Hopkins syndrome and provide data to design larger trials.
How similar studies have performed: Vorinostat produced promising nonclinical results in Rett syndrome models and is an approved drug in other indications, but clinical efficacy in Pitt Hopkins syndrome is novel and unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Subjects ≥3 years of age and ≤ 21 years of age at time of screening 2. Clinical diagnosis of PTHS with documented pathologic mutation in the TCF4 gene 3. 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 4. Has been on a stable regimen of medication or non-pharmacological treatment for at least 4 weeks prior to the baseline visit 5. Has had a stable pattern of seizure activity for 4 weeks before screening 6. Can swallow medication or can take it by gastrostomy tube 7. Can wear actigraphy data logging device on wrist or ankle 8. 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) 9. 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: 1. 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) 2. Has major surgery planned during the study period 3. Pregnant or nursing women 4. Has a history of brain injury, stroke, other cerebrovascular disease or hypoxic-ischemic encephalopathy 5. Has clinically significant abnormal vital signs at screening or baseline 6. Has an abnormal ECG at screening, including clinically significant QT prolongation 7. Has a clinically significant abnormal laboratory value at screening 8. Liver disease or transaminase levels \> 1.5 times the upper limit of the normal range as determined during screening 9. Has a history of malignancy of any organ system within the past 5 years before screening 10. Is participating in or has participated in another clinical trial within 30 days prior to the screening visit 11. Has been treated with growth hormone, IGF-1, or insulin within 12 weeks of baseline 12. Is taking anticoagulant therapy or other HDAC inhibitors 13. Has had any change to their medication or non-pharmacological treatment within 4 weeks prior to the baseline visit 14. Life expectancy of less than 12 months. 15. Has a history of alcoholism or drug/chemical abuse within 2 years before screening. 16. In the investigator's opinion, is inappropriate for this study for any reason
Where this trial is running
Medellín
- Grupo de Investigación Clínica PECET (GIC-PECET) — Medellín, Colombia (Recruiting)
Study contacts
- Study coordinator: Neal I Muni, M.D., MSPH
- Email: neal.muni@unravel.bio
- Phone: +1 857-404-8252
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.