Safety and Efficacy of APL180 in Healthy Volunteers and Patients With Coronary Heart Disease (CHD)

A First-in-human, Randomized, Double-blind, Placebo-controlled, Single-ascending Dose (Healthy Volunteers and CHD Patients) and Multiple Dose (CHD Patients) Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL180

The purpose of this study is to determine: (1) the safety and pharmacokinetics of APL180 administered as a single intravenous infusion in healthy volunteers, and (2) the safety, pharmacokinetics and pharmacodynamics of single and multiple daily intravenous infusions of APL018 in patients with CHD

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Drug: Placebo; Drug: APL180

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • Novartis Investigator Site
• Denmark
  • Birkeroed, Denmark
    • Novartis Investigator Site
• Israel
  • Jerusalem, Israel
    • Novartis Investigator Site
  • Tel-Aviv, Israel
    • Novartis Investigator Site
  • Tzrifin, Israel
    • Novartis Investigator Site
• Netherlands
  • Groningen, Netherlands
    • Novartis Investigator Site
• South Africa
  • Bloemfontein, South Africa
    • Novartis Investigator Site
  • George, South Africa
    • Novartis Investigator Site
  • Port Elizabeth, South Africa
    • Novartis Investigator Site
• United Kingdom
  • Harrow, United Kingdom
    • Novartis Investigator Site
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female healthy volunteers (ages 18-55 years) and patients with CHD (ages 18 to 75 years) on stable statin therapy for at least 8 weeks, with normal liver and kidney function.
• Women who are post-menopausal, surgically sterile, or practicing effective contraception. Additional birth control details to be provided at screening.
• Body mass index (BMI) must be within the range of 20 to 35 for CHD patients or CHD equivalents.
• Clinical CHD:
• Myocardial infarction (MI), angina, revascularization (e.g. CABG, stent) at least 6 months prior to inclusion
• CHD equivalents:
• symptomatic carotid artery disease (e.g. transient ischemic attack or stroke of carotid origin) or peripheral artery disease or abdominal aortic aneurysm or Diabetes Mellitus (HbA1c ≤9)
• 20% 10 year risk of CHD (Framingham point score: ≥16 (men), ≥23 (women))
• Other clinical forms of atherosclerotic disease including >50 percent stenosis on angiography or ultrasound
• Male subjects, when sexually active, using one form of highly effective contraception (e.g. condom)

Exclusion Criteria for both healthy volunteers and patients:

• Smokers (use of tobacco products in the previous 3 months). Smokers who report cigarette use of more then 10 cigarette per day or have a urinary cotinine level greater then 500 ng/ml.
• Pregnancy.
• Use of any prescription drugs within four (4) weeks prior dosing, or over-the-counter (OTC) medication (vitamins, herbal supplements, dietary supplements) within two (2) weeks prior to dosing. Significant illness within two weeks prior to dosing.
• Significant illness within two weeks prior to dosing.
• A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome.
• History of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug or any allergic reaction to prior receipt of protein therapies or vaccines.
• Presence of NYHA Class III or IV CHF or unstable angina pectoris.
• MI or within angioplasty (including stenting), acute coronary syndrome (ACS), unstable angina or arterial embolic disease within 6 months prior to dosing.
• Use of certain medications prohibited by the protocol.
• Uncontrolled diabetes (HbA1c > 9).
• Uncontrolled hypertension (Systolic BP >160 mm Hg and/or Diastolic BP >100 mmHg on two consecutive measurements).
• Liver or kidney disease confirmed by abnormal lab values or function.
• Serum creatine kinase CK (CPK) total > 2x.
• CHD equivalent patients with a history of early positive exercise stress test.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: APL180
Placebo Comparator: 2	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability, pharmacokinetics and effects on biomarkers of HDL function of APL180 after a single and 7-daily infusions in healthy volunteers (HV) and in patients with coronary heart disease (CHD)	throughout the study

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic/pharmacodynamic relationship after a single and 7 daily infusions in CHD patients	throughout the study

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

Helpful Links

• Results for CAPL180A2201 from the Novartis Clinical Trials website

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: December 5, 2007
• First Submitted That Met QC Criteria: December 5, 2007
• First Posted (Estimate): December 6, 2007

Study Record Updates

• Last Update Posted (Actual): December 24, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Apolipoprotein A-I,; Atherosclerosis,; HDL,; Inflammation,
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: CAPL180A2201