Daily oral vorinostat for girls and young women with Rett syndrome
Rett REVOLUTION Trial: An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Rett Syndrome Using an "N of 1" Study Design
This trial will try daily oral vorinostat at two escalating dose levels, using a four-week placebo baseline and an N-of-1 design so each participant serves as her own control, to see if the drug is safe and shows clinical or molecular benefit in girls and young women with typical Rett syndrome.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 15 (estimated) |
| Ages | 6 Years to 21 Years |
| Sex | Female |
| Sponsor | Unravel Biosciences, Inc. Industry-sponsored |
| Locations | 1 site (Medellín) |
| Trial ID | NCT07150013 on ClinicalTrials.gov |
What this trial studies
This is a single-blinded, placebo-controlled, adapted N-of-1 Phase 1 trial testing once-daily oral vorinostat with each participant using a 4-week placebo baseline and then sequential 8-week dosing periods at 80 mg/m2/day and 160 mg/m2/day. Key outcomes include safety and tolerability, changes in clinical and laboratory measures that could indicate benefit, and transcriptome (mRNA) responses. Participants are females aged 6–21 with typical Rett syndrome and a confirmed pathogenic MECP2 mutation who are clinically stable and post-regression. Results will inform dosing, outcome selection, and statistical planning for future trials.
Who should consider this trial
Good fit: Females aged 6–21 with typical Rett syndrome and a documented disease-causing MECP2 mutation who are post-regression, clinically stable, able to take medications orally or by gastrostomy, and willing to wear an actigraphy device are ideal candidates.
Not a fit: Patients without typical Rett (including many males or those lacking a confirmed MECP2 mutation), those with recent clinical deterioration or unstable seizures, or those unable to comply with dosing and monitoring are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, vorinostat could become an oral therapy that improves multiple Rett-related symptoms and molecular markers across organ systems.
How similar studies have performed: Vorinostat showed promising nonclinical efficacy across multiple organ systems in animal models and ranked highly versus trofinetide in the sponsor's screening, but it has not yet been proven effective in people with Rett syndrome.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Female subjects ≥6 years of age and ≤ 21 years of age at time of screening 2. Has typical Rett Syndrome (RTT), based on diagnostic criteria for RTT described in Neul, et.al., 2010 3. Has documented, disease causing mutation in the MeCP2 gene 4. 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 5. Has been on a stable regimen of medication or non-pharmacological treatment for at least 4 weeks prior to the baseline visit; if currently taking trofinetide (Daybue), currently on stable dose for the previous 6 months before screening visit 6. Has had a stable pattern of seizure activity for 4 weeks before screening 7. Can swallow medication or can take it by gastrostomy tube 8. Can wear actigraphy data logging device on wrist or ankle 9. 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) 10. 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 MeCP2 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.