Not yet recruitingRare disease

Study of the Safety, Tolerability and Efficacy of Oral Vafidemstat in Adults with Phelan‑McDermid Syndrome (HOPE‑2)

Verified siteInvestigationalNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study involves adults diagnosed with Phelan-McDermid Syndrome, a rare genetic condition that can cause developmental delays, speech difficulties, and behavioral challenges. Participants will receive the oral medication vafidemstat, supplied in capsule form.

The purpose of the study is to evaluate the safety and tolerability of the medication in this population. Participants will take the capsules daily for a set period, attending regular visits where doctors will check vital signs, perform physical examinations, and record any side effects. Blood tests and a heart rhythm test called an electrocardiogram (ECG) will also be performed to monitor overall health.

In addition to safety checks, the study will use questionnaires such as the Aberrant Behaviour Checklist and the Clinical Global Impression of Severity to track changes in irritability, aggression, and other behaviors. Any thoughts of self‑harm will be assessed with the Columbia‑Suicide Severity Rating Scale (C-SSRS), a questionnaire that helps identify suicidal thoughts. All information collected will be used to determine whether the medication is safe and well‑tolerated for adults with the condition.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Baseline assessment
You will attend an initial visit where a medical professional will record your medical history, perform a physical examination, measure vital signs such as blood pressure and heart rate, and conduct an electrocardiogram (ecg) to check heart activity.
Blood and urine samples will be taken for laboratory tests to establish baseline values for blood cells and chemistry.
You will complete several questionnaires that evaluate your behavior and symptoms, including the aberrant behaviour checklist, the repetitive behaviour scale‑revised, and the phelan‑mcdermid syndrome assessment of severity.
All information collected at this visit will be used as a reference point for later comparisons.
Step 2
Start of medication
You will begin taking vafidemstat in oral capsule form.
The prescribed dose is 1111111 mg per capsule, taken as directed by the study team for the duration of the study.
The medication is taken by mouth; the exact frequency (for example, once daily) will be explained by the study staff.
Step 3
Regular safety monitoring visits
You will return to the clinic at scheduled intervals (for example, every four weeks) while you are taking the study medication.
During each visit, the staff will ask you about any new or worsening symptoms, known as adverse events, and record their number, frequency, and severity.
Vital signs, an ecg, and laboratory tests will be repeated to detect any clinically relevant changes.
If a serious adverse event occurs, additional assessments may be performed, and the study medication may be stopped.
Step 4
Efficacy assessments
At selected visits, you will again complete the behavioral questionnaires that were administered at baseline.
These include the aberrant behaviour checklist irritability subscale, the clinical global impression of severity for anger and aggression, the repetitive behaviour scale‑revised, and other subscales that measure stereotypic behaviour, hyperactivity, inappropriate speech, and social withdrawal.
The results will be compared with your baseline scores to determine any changes in your condition.
Step 5
Continuous safety checks for suicidal thoughts
Throughout the study, you will be asked to answer questions from the columbia – suicide severity rating scale (c‑ssrs), which evaluates whether you have had thoughts of self‑harm or suicidal behaviour.
Any indication of suicidal ideation will be reported immediately and managed according to safety protocols.
Step 6
Final assessment and end of treatment
At the end of the study period, you will undergo a final visit that repeats the physical examination, vital signs, ecg, laboratory tests, and behavioral questionnaires.
The study medication will be discontinued, and the overall safety and efficacy data will be summarized.
You will be thanked for your participation, and any remaining concerns will be addressed by the study team.

Who can join the trial?

5 criteria

Be between 18 and 65 years old when you sign the study consent form.
Have a confirmed diagnosis of Phelan McDermid Syndrome (PMS) that is proven by a genetic test showing either a harmful change (mutation) in the SHANK3 gene or a missing piece of chromosome 22q13.3 that includes part of this gene. These genetic tests can be done with methods such as chromosomal microarray, fluorescence in situ hybridization (FISH), karyotype, or DNA sequencing.
Score 12 or higher on the irritability part of the Aberrant Behaviour Checklist (ABC) during the four weeks before screening, and have this score confirmed at the screening visit. The ABC is a questionnaire used to measure problem behaviors, and the irritability subscale focuses on how often you feel angry or upset.
Provide written informed consent to join the study. If you need help understanding the information, support will be given according to the law. If you cannot give consent yourself, a court‑appointed representative may sign for you.
Have a study caregiver (such as a family member, legal representative, social worker, residential staff, or nurse) who spends at least 4 hours per week with you, can go with you to study visits, and can give accurate information about your health.

Who cannot join the trial?

14 criteria

Unable to complete the required screening tests.
Doctor believes you are not suitable for the study or may not be able to follow the study rules.
If you have another mental health diagnosis (according to the DSM‑5) that has not been stable for at least three months, is currently getting worse, needs new medication or therapy, or might interfere with the study, you cannot join.
Having severe breathing problems (respiratory insufficiency).
Having significant liver problems (hepatic impairment) meaning liver enzyme levels are more than twice the normal range.
Having significant kidney problems (renal insufficiency) meaning the estimated filtration rate is below 90 mL/min/1.73 m².
Having a recent serious heart event (heart attack, unstable angina, severe heart failure class III or IV, or new heart muscle disease) within the past six months.
Having very high blood pressure (uncontrolled hypertension) with a systolic reading of 160 mmHg or higher on two separate measurements.
Having certain heart rhythm disorders, such as type II or type III atrioventricular block, long QT syndrome, problems with the heart’s natural pacemaker (sinus node dysfunction), or a prolonged QT interval (over 450 ms for men or 470 ms for women), unless caused by a known previous surgery issue.
Having uncontrolled diabetes, shown by a glycosylated hemoglobin (HbA1c) level greater than 7.5%.
Having uncontrolled thyroid problems (either too much or too little thyroid hormone) based on lab tests.
Having a low platelet count (platelets less than 150,000 per mm³) or a low neutrophil count (neutrophils less than 2,000 per mm³).
Having any past cancer (malignancy).
Having any past moderate‑to‑severe traumatic brain injury.

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Verified sites

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Hospital General Universitario Gregorio Maranon
Verified
Madrid, Spain

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Investigated drugs

VAFIDEMSTAT is an experimental oral capsule being tested in this study. Participants take the capsule by mouth. The drug is being evaluated to see if it is safe and well‑tolerated for adults who have Phelan‑McDermid Syndrome, a rare genetic condition. Researchers are also looking at whether the medication can improve symptoms of the syndrome. This trial is focused on gathering information about any side effects, how the body handles the drug, and any potential benefits it may provide.

Vafidemstat

What is already known about the treatment

VAFIDEMSTAT - This medication is taken by mouth in capsule form. It is an investigational drug that is currently being studied in a Phase 2a trial and has not yet received regulatory approval. The main purpose is to help adults with Phelan‑McDermid Syndrome, a rare condition that affects development and behavior. Vafidemstat works by blocking an enzyme that changes how genes are turned on or off in brain cells, and it is classified as an LSD1 (lysine‑specific demethylase 1) inhibitor, a type of epigenetic modulator.

Investigated diseases

Phelan‑McDermid syndrome - A rare genetic disorder caused by loss or alteration of the SHANK3 gene, which affects brain development. Children typically show delayed milestones, limited speech, and intellectual disability from an early age. Many also display features of autism, such as difficulty with social interaction and repetitive behaviors. Over time, some individuals may develop seizures, motor coordination problems, or sleep disturbances, and the severity of symptoms can vary as they grow.