Clinical trial NCT05161715: Proof-of-concept, Open-label Study in Patients With Early Alzheimer's Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Early Alzheimer's Disease
Lead sponsor: NewAmsterdam Pharma
Sponsor class: INDUSTRY
First posted: 2021-12-17
Enrollment: 13
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Cerebrospinal Fluid (CSF)
timeFrame: 24 weeks
measure: Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Plasma
timeFrame: 24 weeks
measure: Mean Percent Change in Apolipoprotein-E (ApoE) in Cerebrospinal Fluid (CSF)
timeFrame: 24 weeks
measure: Mean Percent Change in Apolipoprotein-E (ApoE) in Plasma
timeFrame: 24 weeks
measure: Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Baseline
timeFrame: baseline
measure: Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Week 24
timeFrame: Week 24
measure: Small HDL (s-HDL) Particle Concentration in Plasma at Baseline
timeFrame: baseline
measure: Small HDL (s-HDL) Particle Concentration in Plasma at Week 24
timeFrame: Week 24
measure: Mean Percent Change in Cholesterol Efflux Capacity in Cerebrospinal Fluid (CSF)
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Brain Research Center Amsterdam
Study officials:
affiliation: NewAmsterdam Pharma
name: Marc Ditmarsch, MD
role: STUDY_DIRECTOR
References: