Trial Outcomes & Findings for Bryostatin Treatment of Moderately Severe Alzheimer's Disease (NCT NCT04538066)

NCT ID: NCT04538066

Last Updated: 2024-07-31

Results Overview

Treatment emergent adverse events and serious adverse events will be analyzed by treatment group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

122 participants

Primary outcome timeframe

Prior to version 6 of the protocol, final assessments were performed at Week 42, 12 weeks after the last study treatment. The final study visit took place at Week 30 for subjects remaining in the study after the protocol amendment.

Results posted on

2024-07-31

Participant Flow

Twenty-nine medical clinics in the US were selected to recruit study subjects.

Participant milestones

Participant milestones
Measure	Bryostatin 1 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.
Overall Study STARTED	61	61
Overall Study COMPLETED	33	40
Overall Study NOT COMPLETED	28	21

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bryostatin Treatment of Moderately Severe Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bryostatin 1 n=59 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=58 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Total n=117 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical >=65 years	52 Participants n=5 Participants	48 Participants n=7 Participants	100 Participants n=5 Participants
Age, Continuous	74.6 years STANDARD_DEVIATION 7.64 • n=5 Participants	73.1 years STANDARD_DEVIATION 7.69 • n=7 Participants	73.9 years STANDARD_DEVIATION 7.67 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	28 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	30 Participants n=7 Participants	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants	45 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	52 Participants n=5 Participants	53 Participants n=7 Participants	105 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	59 participants n=5 Participants	58 participants n=7 Participants	117 participants n=5 Participants
Body Mass Index	26.53 kg/m2 STANDARD_DEVIATION 4.691 • n=5 Participants	26.89 kg/m2 STANDARD_DEVIATION 4.119 • n=7 Participants	26.71 kg/m2 STANDARD_DEVIATION 4.401 • n=5 Participants

PRIMARY outcome

Timeframe: Prior to version 6 of the protocol, final assessments were performed at Week 42, 12 weeks after the last study treatment. The final study visit took place at Week 30 for subjects remaining in the study after the protocol amendment.

Population: All subjected who received any dose of study drug were included in the safety analysis.

Treatment emergent adverse events and serious adverse events will be analyzed by treatment group.

Outcome measures

Outcome measures
Measure	Bryostatin 1 n=59 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=58 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Bryostatin Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.	Placebo Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.
Safety: Treatment-emergent Adverse Events and Serious Adverse Events for All Randomized Subjects Who Received Any Study Medication Treatment related treatment emergent adverse event (TEAE)	15 number of events	13 number of events	—	—
Safety: Treatment-emergent Adverse Events and Serious Adverse Events for All Randomized Subjects Who Received Any Study Medication Serious TEAE	4 number of events	4 number of events	—	—
Safety: Treatment-emergent Adverse Events and Serious Adverse Events for All Randomized Subjects Who Received Any Study Medication TEAE leading to early discontinuation of study treatment	6 number of events	6 number of events	—	—
Safety: Treatment-emergent Adverse Events and Serious Adverse Events for All Randomized Subjects Who Received Any Study Medication TEAE leading to study termination	3 number of events	3 number of events	—	—

PRIMARY outcome

Timeframe: Primary efficacy analysis at Week 28

Population: All subjects who completed Week 28 were included in the analysis.

The treatment difference in the primary efficacy endpoint of Severe Impairment Battery (SIB). The SIB is used to assess cognition in subjects with moderate and severe AD. It is divided into nine subscales that include attention, language, orientation, memory, praxis, visuospatial ability, construction, social skills, orienting head to name. Non-verbal responses are allowed, thus decreasing the need for language output. Forty questions are included with a point score range of 0-100. Lower scores indicate greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Bryostatin 1 n=31 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=34 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Bryostatin Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.	Placebo Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.
Efficacy: Severe Impairment Battery Total Score Assessment Obtained After Completion of the Second Couse of Treatment (Week 28)	1.7 score on a scale Standard Error 1.44	0.2 score on a scale Standard Error 1.46	—	—

SECONDARY outcome

Timeframe: Week 42 was the final follow-up for study subjects, occurring 16 weeks after the last dose of study drug. Subjects who remained in the study at the time version 6 of the protocol was implemented did not have Week 42 visit.

Population: All subjects who completed Week 42 were analyzed.

The SIB assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Bryostatin 1 n=28 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=36 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Bryostatin Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.	Placebo Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.
Severe Impairment Battery (SIB) Total Score at the End of the Week 42 Follow-up Visit	88.4 score on a scale Standard Error 1.81	84.3 score on a scale Standard Error 1.59	—	—

SECONDARY outcome

Timeframe: Week 13 followed the first 12-week course of study treatment.

Population: All subjects who completed Week 13 were included in the analysis.

The SIB assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Bryostatin 1 n=49 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=49 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Bryostatin Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.	Placebo Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.
The SIB Total Score From Baseline at Week 13	2.4 score on a scale Standard Error 0.87	1.7 score on a scale Standard Error 0.87	—	—

SECONDARY outcome

Timeframe: Weeks 9, 20 and 24 occur during the treatment phase of the study. Week 30 occurred 4 weeks after end of treatment.

Population: All subjects who completed Week 9 were analyzed.

The Severe Impaorment Battery (SIB) assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Bryostatin 1 n=43 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=46 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Bryostatin Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.	Placebo Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.
The Changes From Baseline in SIB Total Scores at Weeks 9, 20, 24, and 30 Week 30	1.7 score on a scale Standard Error 1.54	0.1 score on a scale Standard Error 1.55	—	—
The Changes From Baseline in SIB Total Scores at Weeks 9, 20, 24, and 30 Week 9	1.9 score on a scale Standard Error 0.77	1.3 score on a scale Standard Error 0.80	—	—
The Changes From Baseline in SIB Total Scores at Weeks 9, 20, 24, and 30 Week 20	1.8 score on a scale Standard Error 1.09	0.7 score on a scale Standard Error 1.11	—	—
The Changes From Baseline in SIB Total Scores at Weeks 9, 20, 24, and 30 Week 24	1.7 score on a scale Standard Error 1.26	0.4 score on a scale Standard Error 1.27	—	—

SECONDARY outcome

Timeframe: Weeks 9, 20, 24 and 30

Population: The decline in number of participants analyzed reflects attrition in number of subjects remaining in the trial at each successive timepoint.

MMSE-2 tests selected aspects of cognition on a scale of 0-30. Subjects with MMSE-2 scores of 10-18 will be enrolled in the study. Scores of 10-14 indicate greater impairment than scores of 15-18. Analyses were done comparing all subjects treated with either bryostatin or placebo, and additionally, comparing subjects grouped by MMSE-2 scores of 10-14 and 15-18 treated with either bryostatin or placebo.

Outcome measures

Outcome measures
Measure	Bryostatin 1 n=25 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=27 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Bryostatin Baseline MMSE-2 Score 15-18 n=25 Participants Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.	Placebo Baseline MMSE-2 Score 15-18 n=24 Participants Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.
SIB Total Scores From Baseline at Weeks 9, 20, 24 and 30 for Subjects With Baseline Mini Mental State Exam Version 2 (MMSE-2) Scores of 10-14 and 15-18 Week 9	0.8 scores on a scale Standard Error 1.37	-2.6 scores on a scale Standard Error 1.32	3.3 scores on a scale Standard Error 0.61	4.5 scores on a scale Standard Error 0.66
SIB Total Scores From Baseline at Weeks 9, 20, 24 and 30 for Subjects With Baseline Mini Mental State Exam Version 2 (MMSE-2) Scores of 10-14 and 15-18 Week 20	0.1 scores on a scale Standard Error 1.87	-5.6 scores on a scale Standard Error 1.81	3.9 scores on a scale Standard Error 0.60	5.5 scores on a scale Standard Error 0.62
SIB Total Scores From Baseline at Weeks 9, 20, 24 and 30 for Subjects With Baseline Mini Mental State Exam Version 2 (MMSE-2) Scores of 10-14 and 15-18 Week 24	-0.1 scores on a scale Standard Error 2.18	-6.7 scores on a scale Standard Error 2.11	4.1 scores on a scale Standard Error 0.66	5.8 scores on a scale Standard Error 0.67
SIB Total Scores From Baseline at Weeks 9, 20, 24 and 30 for Subjects With Baseline Mini Mental State Exam Version 2 (MMSE-2) Scores of 10-14 and 15-18 Week 30	-0.4 scores on a scale Standard Error 2.70	-8.3 scores on a scale Standard Error 2.62	4.4 scores on a scale Standard Error 0.79	6.3 scores on a scale Standard Error 0.78

SECONDARY outcome

Timeframe: Slopes will be estimated by using SIB data at Week 0, 5, 9, 13, 15, 20, 24, and 28

Population: All subjects who received any dose of study drug were included in the full analysis set (FAS), 117 subjects.

Individual-specific slopes of total Severe Impairment Battery (SIB) scores will be obtained for all patients. Scores range from 0-100, lower scores indicate greater impairment.

Outcome measures

Outcome measures
Measure	Bryostatin 1 n=57 Participants 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=55 Participants Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Bryostatin Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.	Placebo Baseline MMSE-2 Score 15-18 Subjects with MMSE-2 score of 15-18 at Baseline. The MMSE-2 measures selected aspects of cognition such as memory, orientation, attention, language, and praxis on a scale of 0 to 30. Lower scores indicate greater cognitive impairment than higher scores.
SIB Trends Over Time	-1.2863 scores on a scale / week, averaged for e Interval -2.0944 to -0.4782	-1.3205 scores on a scale / week, averaged for e Interval -2.1226 to -0.5184	—	—

Adverse Events

Bryostatin 1

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bryostatin 1 n=59 participants at risk 20ug Bryostatin will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Bryostatin 1: Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.	Placebo n=58 participants at risk Placebo will be administered over 45 minutes IV. The course of treatment will include 7 doses over the first 12 weeks, followed by a second identical treatment period beginning 30 days after completion of the first treatment period. Placebo: Placebo administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks, followed by a second identical course of treatment beginning 30 days after completion of the first 7-dose course.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) colon tumor	0.00% 0/59 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	1.7% 1/58 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.
Injury, poisoning and procedural complications fractured vertebrae	0.00% 0/59 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	1.7% 1/58 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.
Injury, poisoning and procedural complications fractured R femur	0.00% 0/59 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	1.7% 1/58 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.
Blood and lymphatic system disorders macrocytic anemia d/t B-12 deficiency	1.7% 1/59 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	0.00% 0/58 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) squamous cell carcinoma	1.7% 1/59 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	0.00% 0/58 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.
General disorders acute metabolic encephalopathy	1.7% 1/59 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	0.00% 0/58 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.
Nervous system disorders altered mental state	1.7% 1/59 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	0.00% 0/58 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) colorectal adenoma	0.00% 0/59 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.	1.7% 1/58 • Number of events 1 • Adverse event data was collected from 8/19/2020 (first subject screened) to 11/16/22 (last subject follow-up visit). Prior to the version 6 amendment to the study protocol, adverse events were also collected from participants at week 42, 16 weeks after last dose. After the amendment, adverse events were collected up to week 30, the final study visit, or 30 days after the last dose. Subjects' adverse events were recorded from the date of screening until 30 days after the last study drug dose.

Other adverse events

Additional Information

Chief Medical Officer

Synaptogenix, Inc.

Phone: 973 242-0005

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor has the right to the primary publication. Following primary publication, the PI may publish results from the Study but must submit the publication to Sponsor for approval at least 60 days prior to journal submission. If there is patentable subject matter in the proposed publication, publication shall be delayed to allow for the preparation of a patent application. If primary manuscript is not submitted within 12 months after end of the Study, PI may publish own Study results.
Publication restrictions are in place

Restriction type: OTHER