Phosphorylcholine PC-mAb Effects in Subjects With Elevated Lipoprotein a

Double-blind, Randomised, Placebo-controlled, Multicentre, Phase IIa Study to Investigate the Effect of PC-mAb on Arterial Inflammation in Subjects With Elevated Lipoprotein a

Inflammation and abnormal amount of lipids in the blood are key factors for the development and progression of atherosclerosis (thickening of the artery wall) and cardiovascular disease. Lipoprotein (a) is a pro-inflammatory plasma lipoprotein that is believed to be a risk factor for cardiovascular diseases. Vascular inflammation generates a range of effects, including endothelial dysfunction and migration of white blood cells into the vessel wall, which results in increased risk of cardiovascular events.

This study is designed to assess the effects of multiple monthly intravenous infusions with the fully human antibody called PC-mAb, in subjects with elevated lipoprotein (a).

Study Overview

• Status: Terminated
• Conditions: Cardiovascular Diseases; Arterial Inflammation
• Intervention / Treatment: Drug: PC-mAb; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Department of Vascular Medicine, Academic Medical Center
• Sweden
  • Uppsala, Sweden, 75237
    • CTC Clinical Trial Consultants AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Major inclusion criterion:

• Lp(a) above 50 mg/dL at screening

Major exclusion criteria:

• Medical history of myocardial infarction (MI) or stroke within 12 months of screening
• Ongoing or paroxysmal atrial fibrillation
• Clinically overt heart failure
• Hypertension defined as ≥180/100 mmHg
• Diabetes mellitus
• Systemic autoimmune diseases requiring treatment
• Cancer, excluding basal cell carcinoma, within the last five years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PC-mAb; Phosphorylcholine human monoclonal antibody, i.v. infusions	Drug: PC-mAb; Monthly treatment for 3 months (4 administrations)
PLACEBO_COMPARATOR: Placebo; Placebo to PC-mAb, i.v. infusions	Drug: Placebo; Monthly treatment for 3 months (4 administrations)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monocyte function	Change in transendothelial migration (TEM) in monocytes isolated from treated subjects	From baseline (Day 1) to visit 11 (Day 85)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial inflammation	Change in tissue to background ratio (TBRmax) in common carotid arteries by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)	From baseline (Day 1) to visit 11 (Day 85)
Arterial stiffness	Change in pulse wave velocity (PWV) (m/sec)	From baseline (Day 1) to visit 11 (Day 85)
Adverse events (AEs)/serious AEs (SAEs)	Incidence of AEs/SAEs	From baseline (Day 1) to visit 11 (Day 85)
Vital signs, height	in cm	At screening (Day -63 to -1)
Vital signs, body weight	in kg	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
Vital signs, blood pressure	in mmHg	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
Vital signs, hear rate	in bpm	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
Vital signs, body temperature	in °C	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
Physical examination including review of all organ systems	Any abnormalities will be recorded	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
Electrocardiogram (ECG), PR (PQ)	12-lead ECG; PR (PQ) interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
ECG, QRS	12-lead ECG; QRS interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
ECG, QT	12-lead ECG; QT interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)
ECG, QTcF	12-lead ECG; QTcF interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded	At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143)

Collaborators and Investigators

• Sponsor: Athera Biotechnologies AB
• Investigators: Principal Investigator: Eric SG Stroes, MD, Prof., Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 11, 2017
• Primary Completion (ACTUAL): March 19, 2018
• Study Completion (ACTUAL): July 3, 2018

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (ACTUAL): October 25, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 6, 2018
• Last Update Submitted That Met QC Criteria: July 4, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Lipoprotein a; Phosphorylcholine human monoclonal antibody
• Additional Relevant MeSH Terms: Pathologic Processes; Vascular Diseases; Vasculitis; Cardiovascular Diseases; Inflammation; Arteritis
• Other Study ID Numbers: ATH3G10-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No