Phelan-McDermid Syndrome
Conditions
Keywords
Phelan McDermid Syndrome, NEU-2591-PMS-301, NNZ-2591, Neuren
Brief summary
This Phase 3, open-label extension, multicenter study will evaluate long-term safety, tolerability and efficacy of NNZ-2591 in pediatric participants with Phelan- McDermid Syndrome.
Detailed description
After providing informed consent/assent, pediatric participants with Phelan-McDermid syndrome who participated in previous studies (NEU-2591-PMS-301 and NEU-2591-PMS-001) will undergo assessments for eligibility, baseline characteristics and symptom severity. Once eligibility is confirmed, participants will receive orally administered NNZ-2591 during the 52-week Treatment Period. 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.
Sponsors
Neuren Pharmaceuticals Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 for the antecedent study. 2. Participant must have completed all applicable study visits for the antecedent study in which they participated. 3. Body weight ≥ 10 kg at Screening/Baseline. 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. Participants with seizures must be controlled on no more than 2 anticonvulsant medications (not counting rescue medications). 3. 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. 4. 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. 5. Abnormal liver function laboratory results during the Screening period, as defined by the protocol 6. Abnormal QT interval on Screening ECG as defined by the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term safety and tolerability of NNZ-2591 as assessed by the incidence of adverse events across participants | Baseline through Safety Follow-Up (Month 12) | Incidence of TEAEs, AESI and SAEs across participants |
| Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of ECG parameters events across participants. | Baseline through Month 12 | Change from Baseline in ECG Heart Rate (bpm) |
| Long-term safety and tolerability of NNZ-2591 as assessed by changes from Baseline assessments of vital sign parameters events across participants. | Baseline through Month 12 | Change from Baseline for heart rate (bpm) |
| Long-term safety and tolerability of NNZ-2591 as incidence of abnormal, clinically significant clinical laboratory parameters events across participants. | Baseline through Month 12 | Incidence of abnormal and clinically significant laboratory parameters |
| Long-term safety and tolerability of NNZ-2591 as incidence of abnormal, clinically significant physical examination findings across participants. | Baseline through Month 12 | Incidence of abnormal, clinically significant physical examination findings |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of NNZ-2591 as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) overall score | Months 3 and 12 | Efficacy of NNZ-2591 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 as measured by the change from baseline in the Vineland Adaptive Behavior Scales-3, Interview version (Vineland-3) receptive communication subdomain raw score. | Months 3 and 12 | Efficacy of NNZ-2591 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. |
| Efficacy of NNZ-2591 as measured by the Phelan-McDermid Syndrome Assessment of Change (PMSA-C) domain scores. | Months 3 and 12 | Efficacy of NNZ-2591 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 as measured by the Caregiver Impression of Change (CIC) domain scores. | Months 3 and 12 | Efficacy of NNZ-2591 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 as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) domain scores. | Months 3 and 12 | Efficacy of NNZ-2591 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 as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (PMSA-S) overall score. | Months 3 and 12 | Efficacy of NNZ-2591 as measured by the change from baseline in Phelan-McDermid Syndrome Assessment of Severity (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 as measured by the change from baseline in PMS Clinician Domain Specific Rating Scale (PMS-DSRS) scores. | Months 3 and 12 | Efficacy of NNZ-2591 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
United States
Contacts
CONTACTMedical Information Lead
Outcome results
None listed