Phelan-McDermid Syndrome
Conditions
Keywords
Phelan McDermid Syndrome, NEU-2591-PMS-301, NNZ-2591, Neuren
Brief summary
This Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study will evaluate the efficacy and safety of NNZ-2591 compared to placebo in pediatric participants with Phelan- McDermid Syndrome.
Detailed description
After providing informed consent/assent, pediatric participants with Phelan-McDermid syndrome ages 3-12 years of age will enter the 4-week Screening Period and undergo assessments for eligibility, baseline characteristics and symptom severity. Once eligibility is confirmed, participants will be randomized in a 1:1 ratio to receive either orally administered NNZ-2591 or matching placebo during the 13-week Treatment Period. Subsequently, a 2-week safety follow-up period will occur immediately after the completion of the Treatment Period.
Interventions
DRUGNNZ-2591
The study drug will be administered twice daily orally.
DRUGPlacebo
The study drug will be administered twice daily orally.
Sponsors
Neuren Pharmaceuticals Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) This is a double-blind study in which pediatric participants, caregivers, investigators, and the sponsor are blinded to study drug for the duration of study. Dose escalation, dose modification, and treatment discontinuation will be performed in a blinded manner.
Intervention model description
Phase 3, randomized, double-blind, parallel-group (2-arm), placebo-controlled, multicenter study
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female pediatric participants with Phelan-McDermid syndrome ages 3 to 12 years (inclusive) at the time of signing the informed consent. 2. Clinical diagnosis of Phelan-McDermid syndrome with a documented disease-causing genetic abnormality of SHANK3. 3. Body weight ≥ 10 kg at Screening. 4. Participants with a PMSA-S overall score ≥ 3 at the Screening and Baseline visits. 5. Not actively undergoing regression or loss of skills.
Exclusion criteria
1. Use of exclusionary medication or unstable treatment regimens of acceptable concomitant medications as required by the protocol. 2. Current treatment with more than 3 allowable psychotropic medications. 3. Participants with seizures must be controlled on no more than 2 anticonvulsant medications (not counting rescue medications). 4. Psychotropic medications or any other medication used for a chronic illness (not including antibiotics, pain relievers, anti-diarrheals, and laxatives) with doses and dosing regimen that have not been stable for at least 4 weeks before Screening. If the treatment was discontinued, the discontinuation must have occurred no fewer than 2 weeks before the start of Screening. 5. Any intercurrent seizures in the past 6 months and /or more than 1 seizure in the past 12 months. •A single febrile seizure in the 6 months prior to screening is allowable if no rescue medication was required. 6. Abnormal liver function laboratory results during the Screening period, as defined by the protocol 7. Abnormal QT interval on Screening ECG as defined by the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score. The PMSA-C scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse. |
| Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in the Vineland Adaptive Behavior Scales-3, Interview version (Vineland-3) receptive communication subdomain raw score. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in the Vineland Adaptive Behavior Scales-3, Interview version (Vineland-3) receptive communication subdomain raw score. A higher raw score for the receptive communication subdomain indicates better adaptive behavior. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) overall score. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) overall score. The CIC scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse. |
| Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores. The PMSA-C domain scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse. |
| Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) domain scores. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the Caregiver Impression of Change (CIC) domain scores. The CIC scores range from 1 to 7 with 1 indicating very much improved and 7 indicating very much worse. |
| Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) domain scores. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) domain scores. The PMSA-S scores range from 1 to 7 with 1 indicating typical for age, not at all impaired and 7 among the most severely impaired. |
| Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMSA-S overall score. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMSA-S overall score. The PMSA-S scores range from 1 to 7 with 1 indicating typical for age, not at all impaired and 7 among the most severely impaired. |
| Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMS Clinician Domain Specific Rating Scale (PMS-DSRS) scores. | Week 13 | Efficacy of NNZ-2591 compared with placebo as measured by the change from baseline in PMS Clinician Domain Specific Rating Scale (PMS-DSRS) scores. The PMS-DSRS scores range from 0 to 4 with 0 indicating Symptom Not Present and 4 indicating Very Severe. |
Countries
Canada, United States
Contacts
CONTACTMedical Information Lead
Outcome results
None listed