Early Alzheimer's Disease
Conditions
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.
Interventions
DRUGObicetrapib
10mg obicetrapib
Sponsors
NewAmsterdam Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Open-label
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Cerebrospinal Fluid (CSF) | 24 weeks | Mean percent change from screening (V1) to end of treatment (V6) in ApoA-I in CSF |
| Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Plasma | 24 weeks | Mean percent change in ApoA-I in plasma from baseline (V2) to week 24 (V6) |
| Mean Percent Change in Apolipoprotein-E (ApoE) in Cerebrospinal Fluid (CSF) | 24 weeks | Mean percent change from screening (V1) to end of treatment (V6) in ApoE |
| Mean Percent Change in Apolipoprotein-E (ApoE) in Plasma | 24 weeks | Mean percent change from baseline (V2) to week 24 (V6) in plasma in ApoE |
| Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Baseline | 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) |
| Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Week 24 | Week 24 | Small high-density lipoprotein (s-HDL) particle concentration in CSF measured by Ion Mobility Assay (https://doi.org/10.1002/alz.12649) |
| Small HDL (s-HDL) Particle Concentration in Plasma at Baseline | 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 |
| Small HDL (s-HDL) Particle Concentration in Plasma at Week 24 | 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 |
| Mean Percent Change in Cholesterol Efflux Capacity in Cerebrospinal Fluid (CSF) | 24 weeks | Mean percent change in cholesterol efflux capacity in CSF from screening (V1) to week 24 (V6) |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10mg Obicetrapib 10mg obicetrapib (5mg tablets) administered orally daily for 24 weeks
Obicetrapib: 10mg obicetrapib | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | 10mg Obicetrapib | — |
|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 6.2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 12 Participants | — |
| Sex: Female, Male Male | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 9 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
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
Time frame: 24 weeks
Population: Analysis of PD endpoints in CSF were conducted on 12 patients as the lumbar puncture for one patient was unsuccessful at End of Treatment (Day 168, Visit 6) and no CSF was available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10mg Obicetrapib | Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Cerebrospinal Fluid (CSF) | -8.4 percent change from screening visit | Standard Deviation 13.6 |
p-value: 0.425Wilcoxon (Mann-Whitney)
Primary
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)
Time frame: 24 weeks
Population: For the PD endpoints in plasma, analyses were conducted on all 13 patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10mg Obicetrapib | Mean Percent Change in Apolipoprotein A-I (ApoA-I) in Plasma | 37.5 percent change from baseline | Standard Deviation 25.2 |
p-value: 0.0002Wilcoxon (Mann-Whitney)
Primary
Mean Percent Change in Apolipoprotein-E (ApoE) in Cerebrospinal Fluid (CSF)
Mean percent change from screening (V1) to end of treatment (V6) in ApoE
Time frame: 24 weeks
Population: Analysis of PD endpoints in CSF were conducted on 12 patients as the lumbar puncture for one patient was unsuccessful at End of Treatment (Day 168, Visit 6) and no CSF was available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10mg Obicetrapib | Mean Percent Change in Apolipoprotein-E (ApoE) in Cerebrospinal Fluid (CSF) | 3.9 percent change from screening | Standard Deviation 10.3 |
p-value: 0.0424Wilcoxon (Mann-Whitney)
Primary
Mean Percent Change in Apolipoprotein-E (ApoE) in Plasma
Mean percent change from baseline (V2) to week 24 (V6) in plasma in ApoE
Time frame: 24 weeks
Population: For the PD endpoints in plasma, analyses were conducted on all 13 patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10mg Obicetrapib | Mean Percent Change in Apolipoprotein-E (ApoE) in Plasma | 47.8 percent change from baseline | Standard Deviation 46.9 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Primary
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)
Time frame: 24 weeks
Population: Analysis of PD endpoints in CSF were conducted on 12 patients as the lumbar puncture for one patient was unsuccessful at End of Treatment (Day 168, Visit 6) and no CSF was available for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10mg Obicetrapib | Mean Percent Change in Cholesterol Efflux Capacity in Cerebrospinal Fluid (CSF) | 1.9 percent change from screening | Standard Deviation 24.1 |
p-value: 0.556Wilcoxon (Mann-Whitney)
Primary
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)
Time frame: baseline
Population: Analysis of PD endpoints in CSF were conducted on 12 patients as the lumbar puncture for one patient was unsuccessful at End of Treatment (Day 168, Visit 6) and no CSF was available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10mg Obicetrapib | Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Baseline | 0.542 average relative abundance | Standard Deviation 0.138 |
Primary
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)
Time frame: Week 24
Population: Analysis of PD endpoints in CSF were conducted on 12 patients as the lumbar puncture for one patient was unsuccessful at End of Treatment (Day 168, Visit 6) and no CSF was available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10mg Obicetrapib | Small HDL (s-HDL) Particle Concentration in Cerebrospinal Fluid (CSF) at Week 24 | 0.542 average relative abundance | Standard Deviation 0.106 |
Primary
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
Time frame: baseline
Population: Due to a non-optimal sample preparation procedure, a number of the samples allocated for the small HDL-C particle analysis were lost and therefore no samples were assessed for this measure.
Primary
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
Time frame: Week 24
Population: Due to a non-optimal sample preparation procedure, a number of the samples allocated for the small HDL-C particle analysis were lost and therefore no samples were assessed for this measure.