Familial Hypoalphalipoproteinemia
Conditions
Keywords
Low HDL, Low apoA-I, ABCA-1 mutations, ApoA-I mutations
Brief summary
The purpose of this study is to assess the impact of 29 intravenous infusions of CER-001 vs. placebo, given at weekly (9 infusions) and biweekly (20 infusions) intervals on carotid vessel wall area as measured by 3TMRI, when administered to patients with familial primary hypoalphalipoproteinemia with proven CVD and appropriate background lipid-lowering therapy.
Detailed description
Subjects will be required to have acceptable baseline 3TMRI imaging of carotid arteries. Subjects meeting all eligibility criteria will be randomized to receive CER-001 or placebo (2:1 randomization scheme). Randomized subjects will return weekly for a total of 9 infusions and then biweekly for an additional 20 infusions. 3TMRI imaging of the carotid and femoral arteries will be performed at Week 8, Week 24 (primary endpoint) and Week 48. The total study duration from randomization can range from 50 to 54 weeks for patients completing the study as designed.
Interventions
DRUGCER-001
Recombinant human apoA-I/phospholipid complexes
DRUGPlacebo
0.9% Sodium Chloride Injection, USP
Sponsors
Cerenis Therapeutics, SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Male and female patients, aged 18 and above. * ApoA-I \< 70 mg/dL * Symptomatic or asymptomatic cardiovascular disease * Diagnosis of genetically confirmed HDL-c deficiency due to defects in genes coding for ABCA1 and/or ApoA-1 * Stable doses of lipid lowering therapies for at least 6 weeks prior to baseline procedures Main
Exclusion criteria
* Females of childbearing potential * Patients with LCAT mutations * Patients who experienced recent cardiovascular or cerebrovascular events * Hypertriglyceridemia (\>500 mg/dL) * Severe anemia (Hgb \< 10 g/dL) * Uncontrolled diabetes (HbA1c \>10%) * Congestive heart failure (NYHA class II or higher) * Contraindication for MRI scanning (e.g., implanted metal objects, claustrophobia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | Baseline to Week 24 | Change from baseline to Week 24 carotid MVWA; CER-001 versus placebo; measured by 3TMRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | Baseline to Week 8 | Change from baseline to Week 8 carotid MVWA; CER-001 versus placebo; measured by 3TMRI |
| Change in Target to Background Ratio (TBR) of the Carotid Artery | Baseline to Week 24 | Change from baseline to Week 24 in carotid TBR; CER-001 versus placebo; measured by FDG-PET |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Femoral MVWA | Baseline, Weeks 8, 24 and 48 | Assessed by 3TMRI; change from baseline; CER-001 versus placebo |
Countries
Belgium, Canada, France, Israel, Italy, Netherlands, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CER-001 CER-001 infusion; 9 weekly infusions followed by 20 biweekly infusions
CER-001: Recombinant human apoA-I/phospholipid complexes | 20 |
| Placebo Saline infusion; 9 weekly infusions followed by 20 biweekly infusions
Placebo: 0.9% Sodium Chloride Injection, USP | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
Baseline characteristics
| Characteristic | CER-001 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.65 years | 53.27 years | 53.79 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants | 7 Participants | 22 Participants |
| Mutation ABCA1 Mutation Only | 11 Participants | 5 Participants | 16 Participants |
| Mutation ApoA-I and ABCA1 Mutations | 1 Participants | 1 Participants | 2 Participants |
| Mutation ApoA-I Mutation Only | 8 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 7 Participants | 19 Participants |
| Race (NIH/OMB) White | 8 Participants | 3 Participants | 11 Participants |
| Region of Enrollment Belgium | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Canada | 3 participants | 3 participants | 6 participants |
| Region of Enrollment France | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Israel | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Italy | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Netherlands | 9 participants | 6 participants | 15 participants |
| Region of Enrollment United States | 2 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 13 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 | 0 / 26 |
| other Total, other adverse events | 19 / 20 | 9 / 10 | 9 / 26 |
| serious Total, serious adverse events | 4 / 20 | 0 / 10 | 0 / 26 |
Outcome results
Primary
Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery
Change from baseline to Week 24 carotid MVWA; CER-001 versus placebo; measured by 3TMRI
Time frame: Baseline to Week 24
Population: Modified Intent-to-Treat -- All patients randomized to treatment who have baseline and Week 24 carotid 3TMRI performed
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CER-001 | Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | -0.3 mm2 |
| Placebo | Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | 0.5 mm2 |
p-value: 0.18595% CI: [-1.9, 0.4]Mixed Models Analysis
Secondary
Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery
Change from baseline to Week 8 carotid MVWA; CER-001 versus placebo; measured by 3TMRI
Time frame: Baseline to Week 8
Population: Modified Intent-to-Treat -- All patients randomized to treatment who have baseline and Week 8 carotid 3TMRI performed
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CER-001 | Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | 0.2 mm2 |
| Placebo | Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | -0.5 mm2 |
p-value: 0.21795% CI: [-0.4, 1.8]Mixed Models Analysis
Secondary
Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery
Change from baseline to Week 48 carotid MVWA; CER-001 versus placebo; measured by 3TMRI
Time frame: Baseline to Week 48
Population: Modified Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CER-001 | Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | -0.1 mm2 |
| Placebo | Change in Mean Vessel Wall Area (MVWA) of the Carotid Artery | 0.1 mm2 |
p-value: 0.83295% CI: [-1.6, 1.3]Mixed Models Analysis
Secondary
Change in Target to Background Ratio (TBR) of the Carotid Artery
Change from baseline to Week 24 in carotid TBR; CER-001 versus placebo; measured by FDG-PET
Time frame: Baseline to Week 24
Population: Carotid MRIs were analyzed for TBR in very few patients. Carotid imaging was performed for during the study, but the images were not read, measured or analyzed for TBR by the central imaging lab following termination of the study and closure of the Sponsor company (Cerenis Therapeutics). No funds were made available by the company's Board of Directors to complete these activities. At that time, paired data (baseline and 24 week) was available for only five patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CER-001 | Change in Target to Background Ratio (TBR) of the Carotid Artery | 0.30 Ratio | Standard Deviation 0.16 |
| Placebo | Change in Target to Background Ratio (TBR) of the Carotid Artery | 0.35 Ratio | Standard Deviation 0.215 |
Other Pre-specified
Change in Femoral MVWA
Assessed by 3TMRI; change from baseline; CER-001 versus placebo
Time frame: Baseline, Weeks 8, 24 and 48
Population: Femoral imaging was performed for some patients during the study, but the images were not read, measured or analyzed for Mean Vessel Wall Area by the central imaging lab following termination of the study and closure of the Sponsor company (Cerenis Therapeutics). No funds were made available by the company's Board of Directors to complete these activities.