Hypercholesterolemia
Conditions
Brief summary
Evaluation of the clinical profile (lipid efficacy, safety and PK) across a number of doses of CIVI 007, a PCSK9 inhibitor. Patients to be evaluated will be on a stable background of statin therapy with or without ezetimibe.
Interventions
DRUGCIVI 007
hypercholesterolemia agent
Sponsors
Civi Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Body mass index (BMI) between 18.0 and 40.0 2. Stable (\>4 weeks prior to the Screening Visit) dose of statin therapy with or without ezetimibe 3. Fasting low-density lipoprotein cholesterol (LDL-C): ≥100 mg/dL for those without cardiovascular disease, or ≥70 mg/dL for those with cardiovascular disease. 4. Fasting triglycerides (TGs) \<400 mg/dL Key
Exclusion criteria
1. Women who are pregnant, nursing or breast feeding 2. Currently prescribed a lipid lowering agent other than a statin or ezetimibe. 3. Clinically significant disorder or laboratory abnormality that could contraindicate the administration of study drug, affect compliance, interfere with study evaluations, or confound the interpretation of study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the Pharmacodynamic Effect of CIVI 007 | Baseline, D29, D57, D85 | Percent change from baseline in PCSK9 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the Lipid Efficacy of CIVI 007 | Baseline, Day 29, Day 57, Day 85 | Percent change from baseline in LDL-C |
| Assessment of CIVI 007 Adverse Events (AEs) | Baseline through 2 month follow-up | Incidence of any drug-related AEs |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CIVI 007, Dose A Subcutaneous (SC) injection of a PCSK9 inhibitor- low dose given twice
CIVI 007: hypercholesterolemia agent | 12 |
| CIVI 007, Dose B SC injection of PCSK9 inhibitor- dose titration
CIVI 007: hypercholesterolemia agent | 13 |
| CIVI 007, Dose C SC injection of PCSK9 inhibitor- high dose given twice
CIVI 007: hypercholesterolemia agent | 12 |
| Placebo Placebo SC injection matching PCSK9 inhibitor given twice
CIVI 007: hypercholesterolemia agent | 12 |
| Total | 49 |
Baseline characteristics
| Characteristic | CIVI 007, Dose A | CIVI 007, Dose B | CIVI 007, Dose C | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 8 Participants | 8 Participants | 36 Participants |
| Age, Continuous | 57.7 years STANDARD_DEVIATION 8.06 | 56.4 years STANDARD_DEVIATION 9.48 | 56.3 years STANDARD_DEVIATION 11.63 | 60.3 years STANDARD_DEVIATION 8.93 | 57.6 years STANDARD_DEVIATION 9.44 |
| Background statin therapy High intensity | 7 Participants | 5 Participants | 7 Participants | 7 Participants | 26 Participants |
| Background statin therapy Low intensity | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Background statin therapy Moderate intensity | 2 Participants | 6 Participants | 4 Participants | 3 Participants | 15 Participants |
| Background statin therapy None | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Body mass index | 30.75 kg/m2 STANDARD_DEVIATION 4.432 | 31.50 kg/m2 STANDARD_DEVIATION 4.403 | 31.05 kg/m2 STANDARD_DEVIATION 5.306 | 28.56 kg/m2 STANDARD_DEVIATION 3.893 | 30.48 kg/m2 STANDARD_DEVIATION 4.536 |
| Body mass index category less than 30 kg/m2 | 5 Participants | 5 Participants | 5 Participants | 9 Participants | 24 Participants |
| Body mass index category more or equal to 30 kg/m2 | 7 Participants | 8 Participants | 7 Participants | 3 Participants | 25 Participants |
| Childbearing potential, n | 1 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 13 Participants | 12 Participants | 12 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ezetimibe use | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Fasting LDL-C | 115.3 mg/dL STANDARD_DEVIATION 42.49 | 108.2 mg/dL STANDARD_DEVIATION 27.15 | 102.7 mg/dL STANDARD_DEVIATION 21.35 | 130.0 mg/dL STANDARD_DEVIATION 60.39 | 113.9 mg/dL STANDARD_DEVIATION 40.55 |
| Height | 171.0 cm STANDARD_DEVIATION 11.82 | 176.8 cm STANDARD_DEVIATION 10.58 | 174.9 cm STANDARD_DEVIATION 9 | 170.2 cm STANDARD_DEVIATION 10.4 | 173.3 cm STANDARD_DEVIATION 10.54 |
| PCSK9 | 377.13 ug/L STANDARD_DEVIATION 117.819 | 374.03 ug/L STANDARD_DEVIATION 106.523 | 467.03 ug/L STANDARD_DEVIATION 101.657 | 444.43 ug/L STANDARD_DEVIATION 150.172 | 414.81 ug/L STANDARD_DEVIATION 123.535 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 8 Participants | 10 Participants | 8 Participants | 35 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 3 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 9 Participants | 6 Participants | 31 Participants |
| Taking lower than recommended statin therapy? | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 8 Participants |
| Weight | 89.51 kg STANDARD_DEVIATION 12.011 | 98.55 kg STANDARD_DEVIATION 16.473 | 95.30 kg STANDARD_DEVIATION 18.659 | 82.56 kg STANDARD_DEVIATION 12.327 | 91.62 kg STANDARD_DEVIATION 15.924 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 8 / 12 | 10 / 13 | 6 / 12 | 9 / 12 |
| serious Total, serious adverse events | 1 / 12 | 0 / 13 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Assessment of the Pharmacodynamic Effect of CIVI 007
Percent change from baseline in PCSK9
Time frame: Baseline, D29, D57, D85
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 29 | -4.54 percentage change from baseline |
| Placebo | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 85 | -0.37 percentage change from baseline |
| Placebo | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 57 | -7.42 percentage change from baseline |
| Experimental: CIVI 007, Dose A | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 29 | -71.38 percentage change from baseline |
| Experimental: CIVI 007, Dose A | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 85 | -43.74 percentage change from baseline |
| Experimental: CIVI 007, Dose A | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 57 | -81.08 percentage change from baseline |
| Experimental: CIVI 007, Dose B | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 57 | -85.48 percentage change from baseline |
| Experimental: CIVI 007, Dose B | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 29 | -76.01 percentage change from baseline |
| Experimental: CIVI 007, Dose B | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 85 | -55.89 percentage change from baseline |
| Experimental: CIVI 007, Dose C | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 29 | -82.27 percentage change from baseline |
| Experimental: CIVI 007, Dose C | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 85 | -61.10 percentage change from baseline |
| Experimental: CIVI 007, Dose C | Assessment of the Pharmacodynamic Effect of CIVI 007 | Day 57 | -83.42 percentage change from baseline |
Comparison: Applying the LOCF method (Last Observation Carried Forward) did not result in any changes at Day 29 or Day 57 due to the lack of missing values and resulted in similar results at Day 85.p-value: <0.000195% CI: [-98.95, -70.18]ANCOVA
Comparison: Applying the LOCF method (Last Observation Carried Forward) did not result in any changes at Day 29 or Day 57 due to the lack of missing values and resulted in similar results at Day 85.p-value: <0.000195% CI: [-94.58, -66.29]ANCOVA
Comparison: Applying the LOCF method (Last Observation Carried Forward) did not result in any changes at Day 29 or Day 57 due to the lack of missing values and resulted in similar results at Day 85.p-value: <0.000195% CI: [-99, -70.75]ANCOVA
Secondary
Assessment of CIVI 007 Adverse Events (AEs)
Incidence of any drug-related AEs
Time frame: Baseline through 2 month follow-up
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Assessment of CIVI 007 Adverse Events (AEs) | Mild | 4 Participants |
| Placebo | Assessment of CIVI 007 Adverse Events (AEs) | Severe | 0 Participants |
| Placebo | Assessment of CIVI 007 Adverse Events (AEs) | Moderate | 1 Participants |
| Experimental: CIVI 007, Dose A | Assessment of CIVI 007 Adverse Events (AEs) | Mild | 2 Participants |
| Experimental: CIVI 007, Dose A | Assessment of CIVI 007 Adverse Events (AEs) | Severe | 1 Participants |
| Experimental: CIVI 007, Dose A | Assessment of CIVI 007 Adverse Events (AEs) | Moderate | 1 Participants |
| Experimental: CIVI 007, Dose B | Assessment of CIVI 007 Adverse Events (AEs) | Moderate | 3 Participants |
| Experimental: CIVI 007, Dose B | Assessment of CIVI 007 Adverse Events (AEs) | Mild | 5 Participants |
| Experimental: CIVI 007, Dose B | Assessment of CIVI 007 Adverse Events (AEs) | Severe | 0 Participants |
| Experimental: CIVI 007, Dose C | Assessment of CIVI 007 Adverse Events (AEs) | Mild | 1 Participants |
| Experimental: CIVI 007, Dose C | Assessment of CIVI 007 Adverse Events (AEs) | Severe | 0 Participants |
| Experimental: CIVI 007, Dose C | Assessment of CIVI 007 Adverse Events (AEs) | Moderate | 2 Participants |
Secondary
Assessment of the Lipid Efficacy of CIVI 007
Percent change from baseline in LDL-C
Time frame: Baseline, Day 29, Day 57, Day 85
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Assessment of the Lipid Efficacy of CIVI 007 | Day 29 | -0.86 percentage change from baseline |
| Placebo | Assessment of the Lipid Efficacy of CIVI 007 | Day 57 | -10.85 percentage change from baseline |
| Placebo | Assessment of the Lipid Efficacy of CIVI 007 | Day 85 | -10.08 percentage change from baseline |
| Experimental: CIVI 007, Dose A | Assessment of the Lipid Efficacy of CIVI 007 | Day 57 | -51.21 percentage change from baseline |
| Experimental: CIVI 007, Dose A | Assessment of the Lipid Efficacy of CIVI 007 | Day 29 | -52.37 percentage change from baseline |
| Experimental: CIVI 007, Dose A | Assessment of the Lipid Efficacy of CIVI 007 | Day 85 | -29.66 percentage change from baseline |
| Experimental: CIVI 007, Dose B | Assessment of the Lipid Efficacy of CIVI 007 | Day 57 | -61.18 percentage change from baseline |
| Experimental: CIVI 007, Dose B | Assessment of the Lipid Efficacy of CIVI 007 | Day 85 | -48.65 percentage change from baseline |
| Experimental: CIVI 007, Dose B | Assessment of the Lipid Efficacy of CIVI 007 | Day 29 | -56.44 percentage change from baseline |
| Experimental: CIVI 007, Dose C | Assessment of the Lipid Efficacy of CIVI 007 | Day 85 | -43.51 percentage change from baseline |
| Experimental: CIVI 007, Dose C | Assessment of the Lipid Efficacy of CIVI 007 | Day 57 | -59.18 percentage change from baseline |
| Experimental: CIVI 007, Dose C | Assessment of the Lipid Efficacy of CIVI 007 | Day 29 | -51.70 percentage change from baseline |
Comparison: Similar changes from baseline were observed for Day 29, Day 57, and Day 85 compared to Day 29, Day 57, and Day 85 LOCF.p-value: <0.000195% CI: [-63.06, -32.99]ANCOVA
Comparison: Similar changes from baseline were observed for Day 29, Day 57, and Day 85 compared to Day 29, Day 57, and Day 85 LOCF.p-value: <0.000195% CI: [-64.5, 34.69]ANCOVA
Comparison: Similar changes from baseline were observed for Day 29, Day 57, and Day 85 compared to Day 29, Day 57, and Day 85 LOCF.p-value: <0.000195% CI: [-67.34, -36.64]ANCOVA