AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy
Condition: Phelan-McDermid Syndrome; Epilepsy
MeSH terms: Epilepsy; Chromosome Disorders; Syndrome; Chromosome Deletion
Intervention: AMO-01
Intervention description: Subjects will receive a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Single Group, open label
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 12 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: AMO-01; Shank3; Clinical Trial

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.
    

Eligibility 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.