An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome

NCT07150026 | Recruiting Phase 1

• 2 other identifiers: RVL-001 Study 00320251103997
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Pitt Hopkins Syndrome

Keywords

Pitt Hopkins; n of 1; interventional

Outcome Measures

Primary Outcomes (3)

• Frequency of treatment-related adverse events

  Treatment-related adverse events coded by MedDRA will be compared qualitatively between low dose treatment, high dose treatment, and placebo groups

  20 weeks

• Drug tolerability as measured by number of treatment discontinuations

  The number of patients discontinuing treatment due to adverse events will be assessed between low dose treatment, high dose treatment, and placebo groups

  20 weeks

• Change in transcriptomic profile from baseline, as measured by RNA-seq (transcriptome biomarker analysis)

  Transcriptome biomarker analysis is widely used to assess dynamic changes in biological systems in response to disease processes and applied stimuli, which cannot be captured with genomic sequencing of DNA mutations and variations. Unravel Biosciences has created a proprietary algorithm for analyzing transcriptome data, identifying underlying signatures of disease progression or recovery. The machine learned gene network approach predicted the use of vorinostat based on restoring a transcriptome signature of Rett syndrome toward a healthy state, which was confirmed preclinically and motivated this clinical trial. The same algorithm will be used to assess time-dependent changes in the transcriptome network signature, to evaluate its ability to capture clinical response data and to measure the extent of restoration of a disease signature back to a healthy state in a human relative to pre-clinical models.

  20 weeks

Secondary Outcomes (10)

• Change from baseline on PTHS-specific Clinical Global Impression Improvement Scale (CGI-I)

  20 weeks

• Change from baseline in PTHS-specific Clinical Global Impression Severity Scale (CGI-S)

  20 weeks

• Change from baseline in the Caregiver Impression of Improvement scale (CareGI-I)

  20 weeks

• Change from baseline in the Revised Motor Behavioral Assessment (R-MBA)

  20 weeks

• Change from baseline in Observer-Reported Communication Ability Measure (ORCA)

  20 weeks

Study Arms (3)

Low dose interventional arm

EXPERIMENTAL

vorinostat low dose 80mg/m2/day

Drug: Vorinostat (SAHA)

High dose interventional arm

EXPERIMENTAL

vorinostat 160mg/m2/day dose

Drug: Vorinostat (SAHA)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Vorinostat (SAHA) DRUG

oral suspension

Also known as: suberoylanilide hydroxamic acid

High dose interventional arm; Low dose interventional arm

Placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Unravel Biosciences, Inc.: lead

Study Sites (1)

Grupo de Investigación Clínica PECET (GIC-PECET)

Medellín, Colombia

RECRUITING

MeSH Terms

Conditions

Pitt-Hopkins syndrome

Interventions

Vorinostat

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Neal I Muni, M.D., MSPH

  Unravel Biosciences, Inc.

  STUDY DIRECTOR

Central Study Contacts

Neal I Muni, M.D., MSPH

CONTACT

+1 857-404-8252; neal.muni@unravel.bio

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: September 2, 2025
• Study Start: March 15, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 15, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)