Phase 2
N=32
Multiple Ascending Doses of MEDI6012 in Subjects With Stable Atherosclerotic Cardiovascular Disease
Atherosclerosis · Cardiovascular Disease
Bottom Line
View on ClinicalTrials.gov: NCT03004638 ↗Enrolled (actual)
32
Serious AEs
3.1%
Results posted
Nov 2018
Primary outcome: Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) — 3; 3; 3; 4 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MEDI6012 40 mg (Drug); Placebo (Drug); MEDI6012 120 mg (Drug); MEDI6012 300 mg (Drug); Placebo IV Push (Drug); MEDI6012 IV Push (Drug)
- Age
- Adult, Older Adult · 60+ yrs
- Sex
- All
- Sponsor
- MedImmune LLC
- Primary completion
- Nov 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
3; 3; 3; 4; 0; 3 | — |
| PRIMARY Number of Participants With Abnormal Clinical Laboratory Evaluations Reported as TEAEs |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Vital Signs Reported as TEAEs |
1; 1; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiogram Reported as TEAEs |
0; 0; 1; 0; 0; 0 | — |
| PRIMARY Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for High-density Lipoprotein-cholesterol (HDL-C) |
-6.72; 1355.64; 2874.86; 6465.05; 266.68; 1803.12 | — |
| PRIMARY Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for High-density Lipoprotein-cholesterol Ester (HDL-CE) |
-23.75; 1161.47; 2580.51; 5710.09; 273.03; 1597.12 | — |
| PRIMARY Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Cholesterol Ester |
373.04; 2267.37; 4047.38; 9004.31; 371.75; 2649.56 | — |
| SECONDARY Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein A1 |
821.33; 2440.48; 3740.59; 5302.87; -20.42; 2399.42 | — |
| SECONDARY Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Low-density Lipoprotein Cholesterol (LDL-C). |
-55.96; 1125.45; 1043.39; 3056.76; -78.79; 1364.12 | — |
| SECONDARY Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein B |
-82.95; -40.06; 145.42; -374.38; -239.17; 73.01 | — |
| SECONDARY Change From Baseline in Serum Concentration for MEDI6012 Mass |
0.0000; 16.2684; 0.0000; 0.0000; 0.0000; 3.8646 | — |
| SECONDARY Change From Baseline in Serum Concentration for Total LCAT Activity |
0.2046; 0.0282; 0.6710; 0.9720; 0.0000; 0.5503 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of MEDI6012 |
9.17; 27.5; 83.7; 75.1; 9.63; 27.1 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI6012 |
0.0417; 0.0417; 0.0417; 0.000696; 14.0417; 14.0417 | — |
| SECONDARY Accumulation Ratio (Rac) of MEDI6012 |
1.09; 1.01; 1.02; 0.897; 1.16; 1.21 | — |
| SECONDARY Terminal Half-life (t1/2) of MEDI6012 |
2.7; 1.79; 2.52; 2.6 | — |
| SECONDARY Area Under the Concentration Time Curve to Last Measurable Time Point (AUClast) of MEDI6012 |
10.9; 35.2; 152; 8.98; 48.3; 205 | — |
| SECONDARY Number of Participants With Positive Anti-Drug Antibodies for MEDI6012 |
0; 0; 0; 0; 0; 0 | — |
Summary
To evaluate the safety pharmacokinetics, and pharmacodynamics of repeat weekly dosing of MEDI6012 in subjects with stable atherosclerosis.
Eligibility Criteria
Inclusion Criteria
- Non-childbearing potential
- Diagnosis of stable atherosclerotic CVD
- Currently receiving a stable dose of Statin
Exclusion Criteria
- Unstable cardiovascular condition within 3 months of screening
- Elective arterial revascularization with in the past month
- Any planned arterial revascularization
- Body mass index 45
- Clinically significant ECG that may interfere with the interpretation of serial ECG and QT interval changes at screening
- Chronic kidney disease defined by estimated glomerular filtration rate of less than 30 mL/mim/1.73m2
- Triglycerides greater than 500 mg/dL, LDL-C greater than 160 mg/dL, or HDL-C greater than 60 for males, or 65 for females
- Clinically significant vital sign abnormalities
- Genetic disorder of cholesterol metabolism
- History of overt liver disease
- Poorly controlled endocrine disorder (Diabetes or Thyroid disorder)
- Current or recent use of systemic corticosteroids
- Recent or ongoing infection or febrile illness
- History of active malignancy within 5 years
- History of alcohol or recreational substance abuse in the past 6 months
- Concurrent enrollment in another clinical study of any investigational drug therapy or use of any biologicals within 6 months prior to screening or within 5 half-lives of an investigational agent or biologic, whichever is longer.
Data sourced from ClinicalTrials.gov (NCT03004638). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.