Epilepsy, Phelan-McDermid Syndrome
Conditions
Keywords
AMO-01, Shank3, Clinical Trial
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.
Interventions
DRUGAMO-01
Subjects will receive a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.
Sponsors
Alexander Kolevzon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Group, open label
Eligibility
Sex/Gender
ALL
Age
12 Years to 45 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Weekly Seizure Counts | 4 weeks | 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. |
| Change in CGI - Improvement and Severity Scale | baseline, Week 1, Week 2, and Week 4 | 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. |
| 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. |
| Aberrant Behavior Checklist (ABC) | baseline, Week 1, Week 2, and Week 4 | 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. |
| Repetitive Behavior Scale-Revised (RBS-R) | Baseline, Week 1, Week 2, Week 4 | 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. |
Countries
United States
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. Participants completed study visits. Last participant seen March 2020.
Participants by arm
| Arm | Count |
|---|---|
| AMO-01 Subjects received a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | AMO-01 |
|---|---|
| Age, Continuous | 20.6 years STANDARD_DEVIATION 2.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMO-01 | Number of Adverse Events | 19 events |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMO-01 | Aberrant Behavior Checklist (ABC) | Inappropriate Speech | 1.17 score on a scale | Standard Deviation 2.4 |
| AMO-01 | Aberrant Behavior Checklist (ABC) | Stereotypy | 6.67 score on a scale | Standard Deviation 6.09 |
| AMO-01 | Aberrant Behavior Checklist (ABC) | Irritability | 8.67 score on a scale | Standard Deviation 6.02 |
| AMO-01 | Aberrant Behavior Checklist (ABC) | Lethargy | 15 score on a scale | Standard Deviation 7.13 |
| AMO-01 | Aberrant Behavior Checklist (ABC) | Hyperactivity | 20.33 score on a scale | Standard Deviation 11.34 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Aberrant Behavior Checklist (ABC) | Hyperactivity | 14.33 score on a scale | Standard Deviation 7.79 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Aberrant Behavior Checklist (ABC) | Inappropriate Speech | 1.17 score on a scale | Standard Deviation 2.4 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Aberrant Behavior Checklist (ABC) | Stereotypy | 4.83 score on a scale | Standard Deviation 5.08 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Aberrant Behavior Checklist (ABC) | Lethargy | 12 score on a scale | Standard Deviation 7.9 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Aberrant Behavior Checklist (ABC) | Irritability | 9.33 score on a scale | Standard Deviation 7.89 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Aberrant Behavior Checklist (ABC) | Inappropriate Speech | 0.17 score on a scale | Standard Deviation 0.41 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Aberrant Behavior Checklist (ABC) | Irritability | 6.67 score on a scale | Standard Deviation 3.72 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Aberrant Behavior Checklist (ABC) | Lethargy | 9.83 score on a scale | Standard Deviation 6.01 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Aberrant Behavior Checklist (ABC) | Stereotypy | 4.17 score on a scale | Standard Deviation 3.76 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Aberrant Behavior Checklist (ABC) | Hyperactivity | 15.67 score on a scale | Standard Deviation 9.09 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Aberrant Behavior Checklist (ABC) | Inappropriate Speech | 0 score on a scale | Standard Deviation 0 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Aberrant Behavior Checklist (ABC) | Hyperactivity | 13.83 score on a scale | Standard Deviation 6.27 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Aberrant Behavior Checklist (ABC) | Lethargy | 8.83 score on a scale | Standard Deviation 4.96 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Aberrant Behavior Checklist (ABC) | Irritability | 4.83 score on a scale | Standard Deviation 3.19 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Aberrant Behavior Checklist (ABC) | Stereotypy | 3.17 score on a scale | Standard Deviation 2.93 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMO-01 | Change in CGI - Improvement and Severity Scale | Severity | 5.33 score on a scale | Standard Deviation 0.82 |
| AMO-01 | Change in CGI - Improvement and Severity Scale | Improvement | 0 score on a scale | Standard Deviation 0 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Change in CGI - Improvement and Severity Scale | Improvement | 0.83 score on a scale | Standard Deviation 0.98 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Change in CGI - Improvement and Severity Scale | Severity | 5.33 score on a scale | Standard Deviation 0.82 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Change in CGI - Improvement and Severity Scale | Improvement | 1 score on a scale | Standard Deviation 1.1 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Change in CGI - Improvement and Severity Scale | Severity | 5.33 score on a scale | Standard Deviation 0.82 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Change in CGI - Improvement and Severity Scale | Severity | 5.17 score on a scale | Standard Deviation 0.75 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Change in CGI - Improvement and Severity Scale | Improvement | 1 score on a scale | Standard Deviation 0.89 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Social Communication | 80.83 score on a scale | Standard Deviation 8.61 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Seizures | 62 score on a scale | Standard Deviation 28.43 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sleep | 43.33 score on a scale | Standard Deviation 19.66 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Repetitive Behavior | 70.33 score on a scale | Standard Deviation 21.97 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Thinking and Learning | 86.67 score on a scale | Standard Deviation 6.83 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sensory | 50.83 score on a scale | Standard Deviation 21.78 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Gross Motor | 28.33 score on a scale | Standard Deviation 28.23 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Activities of Daily Living | 78.33 score on a scale | Standard Deviation 10.33 |
| AMO-01 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Speech | 86.83 score on a scale | Standard Deviation 8.13 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Social Communication | 77.5 score on a scale | Standard Deviation 5.24 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Speech | 84.33 score on a scale | Standard Deviation 5.89 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Thinking and Learning | 77.5 score on a scale | Standard Deviation 9.87 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sleep | 29.17 score on a scale | Standard Deviation 17.15 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Seizures | 41.67 score on a scale | Standard Deviation 30.11 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Gross Motor | 26.67 score on a scale | Standard Deviation 24.01 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sensory | 48.33 score on a scale | Standard Deviation 20.17 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Activities of Daily Living | 75 score on a scale | Standard Deviation 10.95 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Repetitive Behavior | 65 score on a scale | Standard Deviation 24.08 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sleep | 43.33 score on a scale | Standard Deviation 24.43 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Gross Motor | 24.17 score on a scale | Standard Deviation 22.45 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Repetitive Behavior | 60.83 score on a scale | Standard Deviation 24.17 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sensory | 52.5 score on a scale | Standard Deviation 22.97 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Activities of Daily Living | 76.5 score on a scale | Standard Deviation 10.75 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Thinking and Learning | 81.67 score on a scale | Standard Deviation 6.83 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Seizures | 47.5 score on a scale | Standard Deviation 34.31 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Social Communication | 77.5 score on a scale | Standard Deviation 6.89 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Speech | 84.17 score on a scale | Standard Deviation 5.85 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Repetitive Behavior | 54 score on a scale | Standard Deviation 25.77 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sleep | 45 score on a scale | Standard Deviation 30.66 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Sensory | 50.33 score on a scale | Standard Deviation 22.82 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Speech | 81.67 score on a scale | Standard Deviation 6.06 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Social Communication | 74.17 score on a scale | Standard Deviation 4.92 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Activities of Daily Living | 78.33 score on a scale | Standard Deviation 8.76 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Thinking and Learning | 78.33 score on a scale | Standard Deviation 2.58 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Gross Motor | 25 score on a scale | Standard Deviation 23.45 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Clinician-completed PMS Domain Specific Causes for Concerns Visual Analogue Scale (VAS) | Seizures | 44.17 score on a scale | Standard Deviation 36.66 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMO-01 | Number of Weekly Seizure Counts | 22.6 seizure event | Standard Deviation 42.9 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Number of Weekly Seizure Counts | 4.3 seizure event | Standard Deviation 7.8 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Number of Weekly Seizure Counts | 15.8 seizure event | Standard Deviation 37.3 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Number of Weekly Seizure Counts | 14.3 seizure event | Standard Deviation 33.2 |
Secondary
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
Population: Subjects received a single 6-hour intravenous infusion for a total dose administration or 120 mg/m2 of AMO-01.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMO-01 | Repetitive Behavior Scale-Revised (RBS-R) | Stereotyped Behavior | 3.67 score on a scale | Standard Deviation 3.5 |
| AMO-01 | Repetitive Behavior Scale-Revised (RBS-R) | Compulsive Behavior | 2.5 score on a scale | Standard Deviation 3.27 |
| AMO-01 | Repetitive Behavior Scale-Revised (RBS-R) | Ritualistic Behavior | 0 score on a scale | Standard Deviation 0 |
| AMO-01 | Repetitive Behavior Scale-Revised (RBS-R) | Sameness Behavior | 2 score on a scale | Standard Deviation 2.68 |
| AMO-01 | Repetitive Behavior Scale-Revised (RBS-R) | Restricted Behavior | 1.83 score on a scale | Standard Deviation 2.4 |
| AMO-01 | Repetitive Behavior Scale-Revised (RBS-R) | Total | 11.83 score on a scale | Standard Deviation 9.26 |
| AMO-01 | Repetitive Behavior Scale-Revised (RBS-R) | Self-Injury | 1.83 score on a scale | Standard Deviation 1.94 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Repetitive Behavior Scale-Revised (RBS-R) | Sameness Behavior | 1.33 score on a scale | Standard Deviation 1.75 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Repetitive Behavior Scale-Revised (RBS-R) | Restricted Behavior | 1.83 score on a scale | Standard Deviation 2.04 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Repetitive Behavior Scale-Revised (RBS-R) | Total | 8.83 score on a scale | Standard Deviation 5.56 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Repetitive Behavior Scale-Revised (RBS-R) | Ritualistic Behavior | 0.17 score on a scale | Standard Deviation 0.41 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Repetitive Behavior Scale-Revised (RBS-R) | Compulsive Behavior | 1.17 score on a scale | Standard Deviation 1.47 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Repetitive Behavior Scale-Revised (RBS-R) | Self-Injury | 1.33 score on a scale | Standard Deviation 1.51 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 1 | Repetitive Behavior Scale-Revised (RBS-R) | Stereotyped Behavior | 3 score on a scale | Standard Deviation 2.68 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Repetitive Behavior Scale-Revised (RBS-R) | Stereotyped Behavior | 3.5 score on a scale | Standard Deviation 2.07 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Repetitive Behavior Scale-Revised (RBS-R) | Ritualistic Behavior | 0.17 score on a scale | Standard Deviation 0.41 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Repetitive Behavior Scale-Revised (RBS-R) | Sameness Behavior | 2 score on a scale | Standard Deviation 2.76 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Repetitive Behavior Scale-Revised (RBS-R) | Compulsive Behavior | 2 score on a scale | Standard Deviation 2.76 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Repetitive Behavior Scale-Revised (RBS-R) | Restricted Behavior | 1.67 score on a scale | Standard Deviation 1.97 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Repetitive Behavior Scale-Revised (RBS-R) | Self-Injury | 2 score on a scale | Standard Deviation 2.45 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 2 | Repetitive Behavior Scale-Revised (RBS-R) | Total | 11.33 score on a scale | Standard Deviation 10.48 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Repetitive Behavior Scale-Revised (RBS-R) | Sameness Behavior | 2.33 score on a scale | Standard Deviation 2.66 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Repetitive Behavior Scale-Revised (RBS-R) | Ritualistic Behavior | 0 score on a scale | Standard Deviation 0 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Repetitive Behavior Scale-Revised (RBS-R) | Compulsive Behavior | 2.5 score on a scale | Standard Deviation 2.81 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Repetitive Behavior Scale-Revised (RBS-R) | Total | 10.83 score on a scale | Standard Deviation 10.87 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Repetitive Behavior Scale-Revised (RBS-R) | Self-Injury | 1.5 score on a scale | Standard Deviation 2.35 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Repetitive Behavior Scale-Revised (RBS-R) | Restricted Behavior | 1.83 score on a scale | Standard Deviation 2.56 |
| Participants With Phelan-McDermid Syndrome (PMS) at Week 4 | Repetitive Behavior Scale-Revised (RBS-R) | Stereotyped Behavior | 2.67 score on a scale | Standard Deviation 2.42 |