Proof of Mechanism Study of MLN1202 on Atherosclerotic Inflammation in Participants With Stable Atherosclerotic Cardiovascular Disease

NCT02388971 | Withdrawn Phase 2

• 2 other identifiers: MLN1202-2006U1111-1159-5742
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the effect of MLN1202 on arterial inflammation in participants with stable atherosclerotic cardiovascular disease (CVD) who are receiving standard-of-care (SOC) therapy.

Conditions

Atherosclerotic Cardiovascular Disease

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• The change in arterial FDG uptake from MLN1202 treatment relative to placebo, comparing pretreatment and 3 month post-treatment time points

  The primary imaging endpoint of interest is the FDG uptake, measured as a target to background ratio (TBR) within the most diseased segment (MDS) of the index vessel.

  Baseline and 3 month post-treatment

Secondary Outcomes (5)

• The change in arterial FDG uptake from MLN1202 treatment relative to placebo, comparing pretreatment and 3 month post-treatment time points in subjects identified using a dominant model of the snip in the MCP-1 polymorphisms [MCP-1 -2518 (rs1024611)].

  Baseline and 3 month post-treatment

• Change from Baseline in Mean Carotid Vessel MDS TBR

  Baseline and Day 82

• Change from Baseline in Mean Active Segment TBR

  Baseline and Day 82

• Change from Baseline in Mean Index Vessel TBR

  Baseline and Day 82

• Change from Baseline in Mean Carotid Vessel TBR

  Baseline and Day 82

Study Arms (2)

MLN1202 Dose

EXPERIMENTAL

MLN1202 Dose, intravenously (IV), once on Days 1, 29 and 57.

Drug: MLN1202

MLN1202 Placebo

EXPERIMENTAL

MLN1202 placebo, intravenously (IV), once on Days 1, 29 and 57.

Drug: Placebo

Interventions

MLN1202 DRUG

MLN1202 solution

MLN1202 Dose

Placebo DRUG

MLN1202 placebo-matching solution

MLN1202 Placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form (including consent for pharmacogenomics \[PGx\] collection) and any required privacy authorization prior to the initiation of any study procedures.
• Is male or female and aged 35 to 80 years, inclusive at Screening.
• Has documented atherosclerotic vascular disease (eg, coronary artery disease (CAD), peripheral arterial disease, aortic atherosclerosis or abdominal aortic aneurysm (\<5 cm), carotid disease, or cerebrovascular disease) and has been clinically stable for at least 3 months prior to Screening. Documentation sufficient to demonstrate presence of atherosclerotic vascular disease will include one or more of the following:
• i. History of myocardial infarction.
• ii. History of stroke.
• iii. Framingham score indicating \>20% 10-year risk in an individual who is age \>55.
• iv. Documentation of atherosclerotic disease by objective diagnostic testing.
• Are willing to undergo 2, 2-deoxy-2-\[\^18F\]-fluoro-D-g1ucose positron emission tomography (FDG PET)/CT scans, have a body weight compatible with their imaging center's PET/CT scanner table limits and be able to tolerate the imaging procedure.
• Are statin naïve or are taking a stable statin dose AND, if taking a statin, are not on a high dose of a high-potency statin. A high-dose of high potency statin is defined as atorvastatin ≥40 mg/day or rosuvastatin ≥20 mg/day. Furthermore, statin dose must be stable for at least 6 weeks prior to Screening FDG PET /CT scan and must not be changed during the remainder of the study.

You may not qualify if:

• Has a history or clinical manifestations of:
• a) Type 1 diabetes mellitus.
• b) Significant heart failure (eg, New York Heart Association class III or IV).
• c) Active or chronic liver disease.
• d) Any chronic systemic inflammatory condition requiring ongoing therapy with anti-inflammatory drugs.
• e) Any history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of this study.
• f) Any infection requiring antibiotic therapy within 6 weeks prior to Screening FDG PET/CT.
• g) Any acute infection within 2 weeks of Screening FDG PET/CT scan.
• h) Impaired renal function (estimated creatinine clearance \<60 ml/min as calculated by the Cockcroft Gault formula). Re-testing may be allowed on a case by case basis.
• Requires ongoing therapy with any systemic anti-inflammatory drugs (except nonsteroidal anti-inflammatory drug \[NSAIDs\]), including systemic anti-inflammatory steroids, methotrexate, colchicine, anti-inflammatory biologics, or any other compound that in the opinion of the investigator has a substantial anti-inflammatory effect.
• Has received treatment with systemic immunosuppressant or systemic anti- inflammatory medications within 6 weeks prior to Screening FDG PET/CT scan.
• Has a history of hypersensitivity or allergies to any component of the study medication or history of hypersensitivity to monoclonal antibodies.
• Has any significant medical condition(s) which, in the investigator's opinion, may interfere with the participant's optimal participation in the study.
• Has poorly controlled blood glucose, defined for the purposes of this study as glycosylated hemoglobin (HbA1c) ≥7.75% at Screening.
• Screening FDG PET/CT scan has inadequate vascular uptake (target to background ratio \[TBR\] \<1.6) in all of the index vessels (ascending aorta, left carotid, right carotid) as assessed by the imaging core laboratory.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Atherosclerosis

Interventions

plozalizumab

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: March 17, 2015
• Study Start: April 1, 2016
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 10, 2015

Record last verified: 2015-12