AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy

An Open-label Study to Investigate the Safety, Tolerability and Efficacy of a Single 6-hour Intravenous Infusion of AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy

The purpose of this study is to investigate the safety, tolerability and efficacy of a single 6-hour intravenous infusion of AMO-01 to treat adolescents and adults with PMS and co-morbid epilepsy. Phelan-McDermid Syndrome (PMS) is a neurodevelopmental disorder characterized by a chromosomal deletion or mutation at 22q13.3 that contains the SHANK3/ProSAP2 gene. A key co-morbidity in PMS is the presence of epilepsy. Currently there are no approved treatments for PMS. Furthermore, there has been relatively little clinical study of pharmacological interventions for PMS. AMO-01 may provide benefit to PMS patients exhibiting behavioral abnormalities and seizures.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Phelan-McDermid Syndrome
• Intervention / Treatment: Drug: AMO-01

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Seaver Autism Center for Research and Treatment at Mount Sinai
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects under study must have a diagnosis of Phelan McDermid syndrome (PMS) with genetic confirmation of pathogenic SHANK3 deletion or mutation.
2. Subjects must be post pubertal males or females aged ≥12 years and ≤45 years at Screening.
3. Subject must have a diagnosis of epilepsy.
4. Subjects must have a syndrome-specific Clinical Global Impression- Severity Score of 4 or greater at Screening
5. Subject's parent or legally authorized representative (LAR) must provide written informed consent before any study related procedures are conducted. Where a parent or LAR provides consent, there must also be assent from the subject (as required by local regulations).
6. Subject's caregiver must be willing and able to support the subject's participation for the duration of the study.
7. Subject's caregiver is able and willing to maintain an accurate and complete daily written seizure diary for the entire duration of the study.

Exclusion Criteria:

1. Receiving medications/therapies not stable (i.e. changed) within 4 weeks prior to Screening. For each enrollee, every effort should be made to maintain stable regimens of allowed concomitant medications and allowed non -medicine based therapies throughout the course of the study, from Screening until the last study assessment.
2. Known hypersensitivity to farnesylated dibenzodiazepinone or any of the formulation components.
3. Subjects with a history of uncontrolled hypotension or hypertension (Polysorbate 80 is a major constituent of AMO-01 and can cause hypotension).
4. Subjects that have received Coumadin or heparin in the 2 weeks preceding Screening.
5. Medical illness or other concern which would cause the investigator to conclude that the subject will not be able to perform the study procedures or assessments or would confound interpretation of data obtained during assessments.
6. Females who are pregnant, lactating or not willing to use a protocol-defined acceptable contraception method if sexually active and not surgically sterile.
7. Males, engaged in sexual relations with a female of child bearing potential, not using an acceptable contraception method if sexually active and not surgically sterile.
8. Clinically significant abnormalities in safety laboratory tests, vital signs or ECG, as measured at Screening (may repeat to confirm).
9. Current clinically significant (as determined by the investigator) neurological, cardiovascular, renal, hepatic, endocrine or respiratory disease that may impact the interpretability of the study results.
10. Current clinically significant (as determined by the investigator) lymphedema that may compromise venous access and/or may have an adverse impact on study drug distribution and clearance.
11. Judged clinically to be at risk of suicide by the investigator.
12. Average QTcF value of >450 msec at Screening (may repeat to confirm).
13. Subjects in whom an indwelling intravenous line could not be established or maintained.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMO-01; Intravenous Infusion	Drug: AMO-01; Subjects will receive a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	An adverse event is defined as any untoward medical occurrence in a study subject, temporally associated with the use of the experimental medication, whether or not considered related to the medication. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the experimental medication. Adverse events will be monitored throughout all 8 weeks of study participation.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS)	9 item visual analogue scale completed by the clinician that scores the severity of concerns in domains that are clinically relevant in PMS. For each subject, the clinician is instructed to identify the top 4 or 5 that are of particular concern and that the clinician would most like to see change during the course of treatment with the study medication. The severity of the clinician's concern in each domain is scored by using a 10 cm visual analogue scale, with anchors of 0 "not at all severe" at the left and 100 "very severe" at the right end.	8 weeks
Number of Weekly Seizure Counts	Seizure frequency was measured by a caregiver-completed seizure diary throughout the duration of the trial. A seizure diary was provided to each family at the screening visit to record each seizure event, its date/time, duration, and type. The study team reviewed the diary at each visit with the caregiver and weekly seizure frequency was calculated. The week 1 seizure count was the number of seizures in the 7 days following the infusion day. Similarly, the week 2 seizure count was the number of seizures in the 7 days between weeks 1 and 2. Lastly, the week 4 seizure count was the sum of seizures in the 14 days between weeks 2 and 4, divided by 2.	4 weeks
Change in CGI - Improvement and Severity Scale	Clinical Global Impressions (CGI) Rating Scales are commonly used to measure symptom severity and global improvement in treatment studies of patients with developmental disorders. There Severity Scale (CGI-S) is a 7-point scale (1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.) that requires the clinician to rate the severity of illness at the time of assessment. The Improvement Scale (CGI-I) is a 7-point scale (1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.) that requires the clinician to assess how much the illness has improved or worsened relative to baseline.	baseline, Week 1, Week 2, and Week 4
Aberrant Behavior Checklist (ABC)	rating scaled used to monitor an array of behavioral features among patients with intellectual disabilities. It takes 15-30 minutes to complete. 16 items, Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). with total from 0 to 48.	baseline, Week 1, Week 2, and Week 4
Repetitive Behavior Scale-Revised (RBS-R)	42-item rating scale that is completed by a parent or caregiver. It reports on the severity of repetitive behaviors. each item scored on 4-point scale: 0-Behavior does not occur, 1-Behavior occurs and is a mild problem, 2-Behavior occurs and is a moderate problem, 3-Behavior occurs and is a severe problem. with total score from 0 (mild) to 126 (severe). Subscale ranges: stereotypic behavior (0 - 27);self-injurious behavior (0 - 24); compulsive behavior (0 - 18); ritualistic/Sameness Behavior (0 - 36); restricted Interests (0 - 9). Higher score in all subscales reflect increasing severity.	Baseline, Week 1, Week 2, Week 4

Collaborators and Investigators

• Sponsor: Alexander Kolevzon
• Investigators: Principal Investigator: Alexander Kolevzon, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2018
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: April 4, 2018
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Clinical Trial; AMO-01; Shank3
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Genetic Diseases, Inborn; Disease; Congenital Abnormalities; Chromosome Aberrations; Monosomy; Aneuploidy; Syndrome; Epilepsy; Chromosome Disorders; Chromosome Deletion
• Other Study ID Numbers: GCO 17-2226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No