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

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ClinicalTrials.gov Identifier: NCT03493607
Recruitment Status : Recruiting
First Posted : April 10, 2018
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Alexander Kolevzon, Icahn School of Medicine at Mount Sinai

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
Phelan-McDermid Syndrome Epilepsy Drug: AMO-01 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single 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 31, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020


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.




Primary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03493607


Contacts
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Contact: Hannah Grosman, BA 212-241-7098 hannah.grosman@mssm.edu

Locations
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United States, New York
Seaver Autism Center for Research and Treatment at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Hannah Grosman, BA    212-241-7098    hannah.grosman@mssm.edu   
Principal Investigator: Alexander Kolevzon, MD         
Sponsors and Collaborators
Alexander Kolevzon
Investigators
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Principal Investigator: Alexander Kolevzon, MD Icahn School of Medicine at Mount Sinai

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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     History of Changes
Other Study ID Numbers: GCO 17-2226
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alexander Kolevzon, Icahn School of Medicine at Mount Sinai:
AMO-01
Shank3
Clinical Trial
Additional relevant MeSH terms:
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Epilepsy
Chromosome Disorders
Syndrome
Chromosome Deletion
Disease
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Monosomy
Aneuploidy
Chromosome Aberrations
Congenital Abnormalities
Genetic Diseases, Inborn