Proof-of-concept, Open-label Study in Patients With Early Alzheimer's Disease

A Phase 2a, Proof-of-Concept, Open-Label Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Obicetrapib in Patients With Early Alzheimer's Disease (Hetero/Homozygote APOE4 Carriers)

A Phase 2a study in men and women with early Alzheimer's disease to evaluate the pharmacodynamics, pharmacokinetics and safety of obicetrapib therapy.

Study Overview

• Status: Completed
• Conditions: Early Alzheimer's Disease
• Intervention / Treatment: Drug: Obicetrapib

Detailed Description

This study will be a proof of concept, Phase 2a study in patients with early Alzheimer's disease (clinical diagnosis of Alzheimer's disease Stage 3 or 4 based on the National Institute on Aging Alzheimer's Association Research Framework criteria) to evaluate the Pharmacodynamic, cognitive effects, Pharmacokinetic, and safety and tolerability of obicetrapib therapy.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Brain Research Center Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• men & women 50-75 years
• post-menopausal or women not of child-bearing potential
• diagnosis of Alzheimer's disease based on National Institute for Aging:
• Biomarker classification A+T+N+ or A+T+N-
• Clinical Stage 3 or 4 with Clinical Dementia Rating score >/= 0.5 & </= 1; mini-mental state examination (MMSE) score >/=20
• Have an APOE genotype of E4/E4 or E3/E4
• not on or on stabilized AD medication
• Patient & study partner willing to sign consent

Exclusion Criteria:

• Other than AD, disorder that may impair cognition
• Contra-indication for MRI

• History of neurological, psychiatric or mental conditions;

  • history stroke
  • MI
  • Type 1 diabetes & Type 2 with HbA1c>8%
  • BP > 150/90 mmHg
  • renal or hepatic impaired
  • hyperaldosteronism
  • cancer
  • depression
  • laboratory abnormalities
  • not able to undergo lumbar puncture
  • taking certain medications including lipid altering

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10mg obicetrapib tablets; 10mg obicetrapib (5mg tablets) administered orally daily for 24 weeks	Drug: Obicetrapib; 10mg obicetrapib; Other Names: TA-8995

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Plasma	Mean percent change in ApoA-I in plasma from baseline (V2) to week 24 (V6)	24 weeks
Mean Percent Change in Apolipoprotein-E (ApoE) in Plasma	Mean percent change from baseline (V2) to week 24 (V6) in plasma in ApoE	24 weeks
Mean Percent Change in Cholesterol Efflux Capacity in Cerebrospinal Fluid (CSF)	Mean percent change in cholesterol efflux capacity in CSF from screening (V1) to week 24 (V6)	24 weeks
Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Cerebrospinal Fluid (CSF)	Mean percent change from screening (V1) to end of treatment (V6) in ApoA-I in CSF	24 weeks
Mean Percent Change in Apolipoprotein-E (ApoE) in Cerebrospinal Fluid (CSF)	Mean percent change from screening (V1) to end of treatment (V6) in ApoE	24 weeks
Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Baseline	Small high-density lipoprotein (s-HDL) particle concentration in cerebrospinal fluid (CSF) measured by Ion Mobility Assay (https://doi.org/10.1002/alz.12649)	baseline
Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Week 24	Small high-density lipoprotein (s-HDL) particle concentration in CSF measured by Ion Mobility Assay (https://doi.org/10.1002/alz.12649)	Week 24
Small HDL (s-HDL) Particle Concentration in Plasma at Baseline	Small high-density lipoprotein (s-HDL) particle concentration plasma measured by Ion Mobility Assay. For more information on the measurement used please refer to this article: https://doi.org/10.1002/alz.12649	baseline
Small HDL (s-HDL) Particle Concentration in Plasma at Week 24	Small high-density lipoprotein (s-HDL) particle concentration in plasma measured by Ion Mobility Assay at Week 24 For more information on the measurement used please refer to this article: https://doi.org/10.1002/alz.12649	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of obicetrapib	Change from baseline to steady-state blood levels of obicetrapib	24 weeks
CSF levels of obicetrapib	Change from baseline to steady-state CSF levels of obicetrapib	24 weeks

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma
• Investigators: Study Director: Marc Ditmarsch, MD, NewAmsterdam Pharma

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2022
• Primary Completion (Actual): May 9, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: TA-8995 AD-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No