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

NCT03493607 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 17-2226
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Phelan-McDermid Syndrome; Epilepsy

Keywords

AMO-01; Shank3; Clinical Trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of Weekly Seizure Counts

  4 weeks

• Change in CGI - Improvement and Severity Scale

  baseline, Week 1, Week 2, and Week 4

• Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS)

  8 weeks

• Aberrant Behavior Checklist (ABC)

  baseline, Week 1, Week 2, and Week 4

• Repetitive Behavior Scale-Revised (RBS-R)

  Baseline, Week 1, Week 2, Week 4

Study Arms (1)

AMO-01

EXPERIMENTAL

Intravenous Infusion

Drug: AMO-01

Interventions

AMO-01 DRUG

Subjects will receive a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.

AMO-01

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects under study must have a diagnosis of Phelan McDermid syndrome (PMS) with genetic confirmation of pathogenic SHANK3 deletion or mutation.
• Subjects must be post pubertal males or females aged ≥12 years and ≤45 years at Screening.
• Subject must have a diagnosis of epilepsy.
• Subjects must have a syndrome-specific Clinical Global Impression- Severity Score of 4 or greater at Screening
• 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).
• Subject's caregiver must be willing and able to support the subject's participation for the duration of the study.
• Subject's caregiver is able and willing to maintain an accurate and complete daily written seizure diary for the entire duration of the study.

You may not qualify if:

• 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.
• Known hypersensitivity to farnesylated dibenzodiazepinone or any of the formulation components.
• Subjects with a history of uncontrolled hypotension or hypertension (Polysorbate 80 is a major constituent of AMO-01 and can cause hypotension).
• Subjects that have received Coumadin or heparin in the 2 weeks preceding Screening.
• 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.
• Females who are pregnant, lactating or not willing to use a protocol-defined acceptable contraception method if sexually active and not surgically sterile.
• 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.
• Clinically significant abnormalities in safety laboratory tests, vital signs or ECG, as measured at Screening (may repeat to confirm).
• 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.
• 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.
• Judged clinically to be at risk of suicide by the investigator.
• Average QTcF value of \>450 msec at Screening (may repeat to confirm).
• Subjects in whom an indwelling intravenous line could not be established or maintained.

Sponsors & Collaborators

• Alexander Kolevzon: lead

Study Sites (2)

Seaver Autism Center for Research and Treatment at Mount Sinai

New York, New York, 10029, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome; Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Christina Layton
• Organization: Icahn School of Medicine at Mount Sinai

christina.layton@mssm.edu

212-241-6231

Study Officials

• Alexander Kolevzon, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Director, Associate Professor, Seaver Autism Center for Research and Treatment

Model Details: Single Group, open label

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: April 10, 2018
• Study Start: May 30, 2018
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: June 27, 2025
• Results First Posted: June 22, 2021

Record last verified: 2025-06

Locations

US (2)