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CompletedNCT03493607Updated Jun 27, 2025Results posted

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

A Phase 2 interventional study of AMO-01 in Phelan-McDermid Syndrome and Epilepsy, sponsored by Alexander Kolevzon. Completed at 2 sites in United States. Open to participants aged 12 Years to 45 Years. Per ClinicalTrials.gov, last updated 2025-06-27.

Sponsored by Alexander Kolevzon · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
6
Allocation
Not applicable
Ages
12 Years to 45 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Phelan-McDermid Syndrome
  • Epilepsy

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Keywords

  • AMO-01
  • Shank3
  • Clinical Trial
03

Who can participate

Ages eligible
12 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
6 participants (actual)

Study arms

  • Experimental
    AMO-01

    Intravenous Infusion

    Drug: AMO-01

Interventions

  • DrugAMO-01

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

05

What researchers measure

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.

    Time frame: 8 weeks

Secondary outcomes

  1. 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.

    Time frame: 4 weeks

  2. 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.

    Time frame: baseline, Week 1, Week 2, and Week 4

  3. 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.

    Time frame: 8 weeks

  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.

    Time frame: baseline, Week 1, Week 2, and Week 4

  5. 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.

    Time frame: Baseline, Week 1, Week 2, Week 4

06

Results

Posted Jun 22, 2021

Participant flow

Recruitment began in Feb 2017, with first enrollment in May of 2018. Study was opened for enrollment through Jan 2021 when decision was made to close study due to low enrollment. Participants completed study visits. Last participant seen March 2020.

Participant flow — Overall Study
MilestoneAMO-01
Started6
Completed6
Not completed0

Outcome measures

PrimaryNumber 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.

Time frame:
8 weeks
Reported as:
Number · events
Number of Adverse Events
eventsAMO-01
Number of Adverse Events19
SecondaryNumber 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.

Time frame:
4 weeks
Reported as:
Mean · seizure event
Number of Weekly Seizure Counts
seizure eventParticipants With Phelan-McDermid Syndrome (PMS) at BaselineParticipants With Phelan-McDermid Syndrome (PMS) at Week 1Participants With Phelan-McDermid Syndrome (PMS) at Week 2Participants With Phelan-McDermid Syndrome (PMS) at Week 4
Number of Weekly Seizure Counts22.6 ± 42.94.3 ± 7.815.8 ± 37.314.3 ± 33.2
SecondaryChange 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.

Time frame:
baseline, Week 1, Week 2, and Week 4
Reported as:
Mean · score on a scale
Change in CGI - Improvement and Severity Scale
score on a scaleParticipants With Phelan-McDermid Syndrome (PMS) at BaselineParticipants With Phelan-McDermid Syndrome (PMS) at Week 1Participants With Phelan-McDermid Syndrome (PMS) at Week 2Participants With Phelan-McDermid Syndrome (PMS) at Week 4
Improvement0 ± 00.83 ± 0.981 ± 1.11 ± 0.89
Severity5.33 ± 0.825.33 ± 0.825.33 ± 0.825.17 ± 0.75
SecondaryClinician-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.

Time frame:
8 weeks
Reported as:
Mean · score on a scale
Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS)
score on a scaleParticipants With Phelan-McDermid Syndrome (PMS) at BaselineParticipants With Phelan-McDermid Syndrome (PMS) at Week 1Participants With Phelan-McDermid Syndrome (PMS) at Week 2Participants With Phelan-McDermid Syndrome (PMS) at Week 4
Speech86.83 ± 8.1384.33 ± 5.8984.17 ± 5.8581.67 ± 6.06
Thinking and Learning86.67 ± 6.8377.5 ± 9.8781.67 ± 6.8378.33 ± 2.58
Seizures62 ± 28.4341.67 ± 30.1147.5 ± 34.3144.17 ± 36.66
Gross Motor28.33 ± 28.2326.67 ± 24.0124.17 ± 22.4525 ± 23.45
Repetitive Behavior70.33 ± 21.9765 ± 24.0860.83 ± 24.1754 ± 25.77
Social Communication80.83 ± 8.6177.5 ± 5.2477.5 ± 6.8974.17 ± 4.92
Sensory50.83 ± 21.7848.33 ± 20.1752.5 ± 22.9750.33 ± 22.82
Activities of Daily Living78.33 ± 10.3375 ± 10.9576.5 ± 10.7578.33 ± 8.76
Sleep43.33 ± 19.6629.17 ± 17.1543.33 ± 24.4345 ± 30.66
SecondaryAberrant 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.

Time frame:
baseline, Week 1, Week 2, and Week 4
Reported as:
Mean · score on a scale
Aberrant Behavior Checklist (ABC)
score on a scaleParticipants With Phelan-McDermid Syndrome (PMS) at BaselineParticipants With Phelan-McDermid Syndrome (PMS) at Week 1Participants With Phelan-McDermid Syndrome (PMS) at Week 2Participants With Phelan-McDermid Syndrome (PMS) at Week 4
Irritability8.67 ± 6.029.33 ± 7.896.67 ± 3.724.83 ± 3.19
Lethargy15 ± 7.1312 ± 7.99.83 ± 6.018.83 ± 4.96
Stereotypy6.67 ± 6.094.83 ± 5.084.17 ± 3.763.17 ± 2.93
Hyperactivity20.33 ± 11.3414.33 ± 7.7915.67 ± 9.0913.83 ± 6.27
Inappropriate Speech1.17 ± 2.41.17 ± 2.40.17 ± 0.410 ± 0
SecondaryRepetitive 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.

Time frame:
Baseline, Week 1, Week 2, Week 4
Reported as:
Mean · score on a scale
Repetitive Behavior Scale-Revised (RBS-R)
score on a scaleParticipants With Phelan-McDermid Syndrome (PMS) at BaselineParticipants With Phelan-McDermid Syndrome (PMS) at Week 1Participants With Phelan-McDermid Syndrome (PMS) at Week 2Participants With Phelan-McDermid Syndrome (PMS) at Week 4
Stereotyped Behavior3.67 ± 3.53 ± 2.683.5 ± 2.072.67 ± 2.42
Self-Injury1.83 ± 1.941.33 ± 1.512 ± 2.451.5 ± 2.35
Compulsive Behavior2.5 ± 3.271.17 ± 1.472 ± 2.762.5 ± 2.81
Ritualistic Behavior0 ± 00.17 ± 0.410.17 ± 0.410 ± 0
Sameness Behavior2 ± 2.681.33 ± 1.752 ± 2.762.33 ± 2.66
Restricted Behavior1.83 ± 2.41.83 ± 2.041.67 ± 1.971.83 ± 2.56
Total11.83 ± 9.268.83 ± 5.5611.33 ± 10.4810.83 ± 10.87

Adverse events

Collected over 8 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AMO-010/6 (0%)0/6 (0%)4/6 (66.7%)
Most frequent other events
Showing 10 of 17
Most frequent other events
EventAMO-01
Increased appetiteMetabolism and nutrition disorders2/6
SeizureNervous system disorders2/6
ConstipationGastrointestinal disorders1/6
Sleep IssuesGeneral disorders1/6
Congestion/CoughRespiratory, thoracic and mediastinal disorders1/6
HeadacheGeneral disorders1/6
CellulitisSkin and subcutaneous tissue disorders1/6
Redness on handsSkin and subcutaneous tissue disorders1/6
Decreased appetite/weight lossMetabolism and nutrition disorders1/6
Viral InfectionInfections and infestations1/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)AMO-01
Mean20.6 ± 2.07
Sex: Female, Male
Sex: Female, Male(Participants)AMO-01
Female3
Male3
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AMO-01
Hispanic or Latino0
Not Hispanic or Latino6
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)AMO-01
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White6
More than one race0
Unknown or Not Reported0
07

Study locations

2 sites
  • Seaver Autism Center for Research and Treatment at Mount Sinai
    New York, New York 10029, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jun 1, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT03493607
Lead sponsor
Alexander Kolevzon
Responsible party
Alexander Kolevzon (Clinical Director, Associate Professor, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai) — Sponsor-investigator
First posted
Apr 10, 2018
Start date
May 30, 2018
Primary completion
Mar 31, 2020
Completion
Mar 31, 2020
Results posted
Jun 22, 2021
Last update
Jun 27, 2025

Study contacts

Alexander Kolevzon, MD
principal investigator · Icahn School of Medicine at Mount Sinai

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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