Trial Outcomes & Findings for Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease (NCT NCT04552795)

Last Updated: 2024-08-09

Results Overview

The extent of 3TC target engagement was measured by calculating the change in reverse transcriptase activity in plasma of participants at baseline compared to week 24 using a modified version of the EnzCheck Reverse Transcriptase (RT) Assay.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Baseline to 24 weeks

Results posted on

2024-08-09

Participant Flow

Participants were recruited from University of Texas Health San Antonio outpatient clinics and through local flier/newspaper advertisements.

Participant milestones

Participant milestones
Measure	Open-Label 3TC 12 subjects will be administered a 300mg once daily oral tablet of 3TC for 24 weeks.
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-Label 3TC n=12 Participants 12 subjects will receive 3TC, 300-mg, daily for 24 weeks. 3TC: 12 subjects will be administered 3TC, 300mg once daily, via an oral tablet for 24 weeks.
Age, Customized Average age (min, max)	69.4 years n=99 Participants
Age, Customized Age group · <= 65 years of age	3 Participants n=99 Participants
Age, Customized Age group · 65 - 74 years of age	5 Participants n=99 Participants
Age, Customized Age group · 75 - 84 years of age	4 Participants n=99 Participants
Sex: Female, Male Female	9 Participants n=99 Participants
Sex: Female, Male Male	3 Participants n=99 Participants
Race/Ethnicity, Customized Race · White, non-Hispanic	9 Participants n=99 Participants
Race/Ethnicity, Customized Race · White, Hispanic	1 Participants n=99 Participants
Race/Ethnicity, Customized Race · African American	1 Participants n=99 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=99 Participants
Education Level	15.3 years STANDARD_DEVIATION 2.4 • n=99 Participants
Past Medical History <= 1 Comorbidities	2 Participants n=99 Participants
Past Medical History 2+ Comorbidities	10 Participants n=99 Participants
Duration of Symptoms Prior to Trial <= 1 year	1 Participants n=99 Participants
Duration of Symptoms Prior to Trial 1-2 years	2 Participants n=99 Participants
Duration of Symptoms Prior to Trial 3+ years	2 Participants n=99 Participants
Duration of Symptoms Prior to Trial Unknown	7 Participants n=99 Participants
Average BMI	25.2 kg/m^2 STANDARD_DEVIATION 4.6 • n=99 Participants
Concurrent Treatment with Donepezil	7 Participants n=99 Participants

PRIMARY outcome

Timeframe: Baseline to 24 weeks

Outcome measures

Outcome measures
Measure	Open-Label 3TC n=12 Participants 12 subjects administered once daily 300 mg 3TC for 24 weeks	POST-Treatment Values after 24 weeks of 3TC administration
Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants	-0.0074 Enzyme units Standard Error 0.03	—

PRIMARY outcome

Timeframe: 24 weeks

Population: Three subjects removed due to missed blood or CSF draw; one subject removed based on the ROUT method of outlier analysis.

CNS penetration was calculated based on the ratio of CSF to plasma levels of 3TC after 24 weeks of 3TC using High Performance Liquid Chromatography with tandem Mass Spectrometry (HPLC/MS/MS).

Outcome measures

Outcome measures
Measure	Open-Label 3TC n=7 Participants 12 subjects administered once daily 300 mg 3TC for 24 weeks	POST-Treatment Values after 24 weeks of 3TC administration
3TC CNS Penetration	0.502 ng/mL Interval 0.0215 to 0.85	—

SECONDARY outcome

Timeframe: Baseline to 24 weeks

The Preclinical Alzheimer Cognitive Composite (PACC-5) score is calculated as a mean normative Z-score across five measures, including MMSE (0-30), Logical Memory Delayed Recall (0-25), Digit-Symbol Coding Test (0-93), Category Fluency, and Free and Cued Selective Reminding Test (0-96). Although typically relegated to individuals with prodromal and asymptomatic disease, the PACC-5 was included given its sensitivity to Alzheimer's disease-specific cognitive change.To calculate the Z score for each patient; the formula is Z = (x - M)/SD, where x is the patient's verbal memory raw score and M and SD are the estimates from the previous step. Positive Z values indicate scores that are greater than the mean of the pooled sample, and negative values indicate scores that are less than the pooled mean.A Z-score of zero represents the mean for this study population. Negative values mean a worse outcome than the standard population.

Outcome measures

Outcome measures
Measure	Open-Label 3TC n=12 Participants 12 subjects administered once daily 300 mg 3TC for 24 weeks	POST-Treatment n=12 Participants Values after 24 weeks of 3TC administration
Change in Dementia Severity From Baseline to Week 24 of Treatment Based on the PACC-5 Z-score	-1.59 Z-score Interval -2.0 to -0.59	-1.59 Z-score Interval -2.0 to -1.2

SECONDARY outcome

Timeframe: Baseline to Week 24

Incidence of adverse and serious adverse events potentially due to study drug

Outcome measures

Outcome measures
Measure	Open-Label 3TC n=12 Participants 12 subjects administered once daily 300 mg 3TC for 24 weeks	POST-Treatment Values after 24 weeks of 3TC administration
Incidence of Treatment-Emergent Adverse Events No adverse events	11 Participants	—
Incidence of Treatment-Emergent Adverse Events Gastrointestinal bleeding due to peptic ulcer	1 Participants	—

SECONDARY outcome

Timeframe: Baseline to Week 24

Blood pressure, heart rate, temperature, and respiration, are measured and any significant change of any of these vital signs that show a significant change from the baseline value are reported as an event.

Outcome measures

Outcome measures
Measure	Open-Label 3TC n=12 Participants 12 subjects administered once daily 300 mg 3TC for 24 weeks	POST-Treatment Values after 24 weeks of 3TC administration
Incidence of Treatment-Emergent Abnormal Vital Signs	0 Events	—

Adverse Events

Open-Label 3TC

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open-Label 3TC n=12 participants at risk 12 subjects administered once daily 300 mg 3TC for 24 weeks
Gastrointestinal disorders Gastrointestinal bleeding	8.3% 1/12 • Number of events 12 • 28 weeks

Other adverse events

Other adverse events
Measure	Open-Label 3TC n=12 participants at risk 12 subjects administered once daily 300 mg 3TC for 24 weeks
Infections and infestations SARS-CoV-2 Infection	16.7% 2/12 • Number of events 2 • 28 weeks
Nervous system disorders Mild headache	16.7% 2/12 • Number of events 2 • 28 weeks
Nervous system disorders Mild fatigue	8.3% 1/12 • Number of events 1 • 28 weeks
Musculoskeletal and connective tissue disorders Mild muscle pain	8.3% 1/12 • Number of events 1 • 28 weeks

Additional Information

Bess Frost, PhD

UT Health San Antonio

Phone: 210-562-5037

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place