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

Sponsor
Alexander Kolevzon (Other)
Overall Status
Completed
CT.gov ID
NCT03493607
Collaborator
(none)
6
2
1
22
3
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Single Group, open labelSingle Group, open label
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
May 30, 2018
Actual Primary Completion Date :
Mar 31, 2020
Actual Study Completion Date :
Mar 31, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Number of Adverse Events [8 weeks]

    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.

Secondary Outcome Measures

  1. Change in CGI - Improvement Scale [baseline and 8 weeks]

    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 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.

  2. Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) [8 weeks]

    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.

  3. Top 3 Caregiver Concerns VAS [4 weeks]

    The Top 3 concerns visual analogue scale allows caregivers to identify their main three causes of concern, related to the subject's PMS. Caregivers will be asked to rate each of the three causes for concern by drawing a vertical mark on a 10 cm long visual analogue scale, with anchors of 0 "not at all severe" at the left end and 100 "very severe" at the right end.

  4. Aberrant Behavior Checklist (ABC) [4 weeks]

    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.

  5. Repetitive Behavior Scale-Revised (RBS-R) [4 weeks]

    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).

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years to 45 Years
Sexes Eligible for Study:
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:
  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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Seaver Autism Center for Research and Treatment at Mount Sinai New York New York United States 10029
2 Texas Children's Hospital Houston Texas United States 77030

Sponsors and Collaborators

  • Alexander Kolevzon

Investigators

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

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Alexander Kolevzon, Clinical Director, Associate Professor, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:
NCT03493607
Other Study ID Numbers:
  • GCO 17-2226
First Posted:
Apr 10, 2018
Last Update Posted:
Jun 22, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Alexander Kolevzon, Clinical Director, Associate Professor, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details 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. Last participant seen March 2020.
Pre-assignment Detail
Arm/Group Title AMO-01
Arm/Group Description Subjects received a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.
Period Title: Overall Study
STARTED 6
COMPLETED 6
NOT COMPLETED 0

Baseline Characteristics

Arm/Group Title AMO-01
Arm/Group Description Subjects received a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.
Overall Participants 6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
20.82
(2.2)
Sex: Female, Male (Count of Participants)
Female
3
50%
Male
3
50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
Not Hispanic or Latino
6
100%
Unknown or Not Reported
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
Asian
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
Black or African American
0
0%
White
6
100%
More than one race
0
0%
Unknown or Not Reported
0
0%

Outcome Measures

1. Primary Outcome
Title Number of Adverse Events
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title AMO-01
Arm/Group Description Subjects received a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.
Measure Participants 6
Number [events]
19
2. Secondary Outcome
Title Change in CGI - Improvement Scale
Description 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 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 and 8 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
3. Secondary Outcome
Title Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS)
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
4. Secondary Outcome
Title Top 3 Caregiver Concerns VAS
Description The Top 3 concerns visual analogue scale allows caregivers to identify their main three causes of concern, related to the subject's PMS. Caregivers will be asked to rate each of the three causes for concern by drawing a vertical mark on a 10 cm long visual analogue scale, with anchors of 0 "not at all severe" at the left end and 100 "very severe" at the right end.
Time Frame 4 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
5. Secondary Outcome
Title Aberrant Behavior Checklist (ABC)
Description 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 4 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description
6. Secondary Outcome
Title Repetitive Behavior Scale-Revised (RBS-R)
Description 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).
Time Frame 4 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description

Adverse Events

Time Frame 8 weeks
Adverse Event Reporting Description
Arm/Group Title AMO-01
Arm/Group Description Subjects received a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.
All Cause Mortality
AMO-01
Affected / at Risk (%) # Events
Total 0/6 (0%)
Serious Adverse Events
AMO-01
Affected / at Risk (%) # Events
Total 0/6 (0%)
Other (Not Including Serious) Adverse Events
AMO-01
Affected / at Risk (%) # Events
Total 4/6 (66.7%)
Ear and labyrinth disorders
Ear Infection 1/6 (16.7%)
Gastrointestinal disorders
Constipation 1/6 (16.7%)
General disorders
Sleep Issues 1/6 (16.7%)
Headache 1/6 (16.7%)
Infections and infestations
Viral Infection 1/6 (16.7%)
Injury, poisoning and procedural complications
Drowsiness after infusion 1/6 (16.7%)
Flushing in face and hand 1/6 (16.7%)
Metabolism and nutrition disorders
Decreased appetite/weight loss 1/6 (16.7%)
Increased appetite 2/6 (33.3%)
Nervous system disorders
Mouth movement, possible tic 1/6 (16.7%)
Seizure 2/6 (33.3%)
Psychiatric disorders
Increased rubbing/repetitive behaviors 1/6 (16.7%)
Motor Stereotypes 1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Congestion/Cough 1/6 (16.7%)
Skin and subcutaneous tissue disorders
Cellulitis 1/6 (16.7%)
Redness on hands 1/6 (16.7%)
Rash on nect 1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Investigators agree not to publish reports, abstracts, or other data compilations concerning the Study before the first multi-site publication by Sponsor. If there is no multi-site publication within 18 months after the Study has been completed or terminated at all Study locations, Principal Investigator shall have the right to publish and or present the results of the Study generated or collected at Study Site(s) (but not the results of any other Study location).

Results Point of Contact

Name/Title Christina Layton
Organization Icahn School of Medicine at Mount Sinai
Phone 212-241-6231
Email christina.layton@mssm.edu
Responsible Party:
Alexander Kolevzon, Clinical Director, Associate Professor, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:
NCT03493607
Other Study ID Numbers:
  • GCO 17-2226
First Posted:
Apr 10, 2018
Last Update Posted:
Jun 22, 2021
Last Verified:
May 1, 2021