GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound (GLAGOV)

• ClinicalTrials.gov Identifier: NCT01813422
• Recruitment Status: Completed
• First Posted: March 19, 2013
• Results First Posted: January 4, 2018
• Last Update Posted: February 20, 2019
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: March 15, 2013
• First Posted Date: March 19, 2013
• Results First Submitted Date: December 4, 2017
• Results First Posted Date: January 4, 2018
• Last Update Posted Date: February 20, 2019
• Actual Study Start Date: April 18, 2013
• Actual Primary Completion Date: July 12, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 4, 2017)

Change From Baseline in Percent Atheroma Volume at Week 78 [ Time Frame: Baseline and week 78 ]

Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. The extent of atherosclerosis was expressed as percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery, calculated as the percentage of the total vessel volume occupied by atheroma.

• Original Primary Outcome Measures (submitted: March 15, 2013): Nominal change in PAV from baseline to 78 weeks post randomization, as determined by intravascular ultrasound (IVUS) [ Time Frame: 78 weeks ]

Current Secondary Outcome Measures (submitted: December 4, 2017)

• Change From Baseline in Total Atheroma Volume at Week 78 [ Time Frame: Baseline and week 78 ]
  Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. Total atheroma volume (TAV) in a ≥ 40 mm segment of the targeted coronary artery was calculated as the average plaque area over the number of images that were evaluated by IVUS multiplied by the median vessel length to compensate for differences in segment length between participants.
• Percentage of Participants With Regression in Percent Atheroma Volume [ Time Frame: Baseline and week 78 ]
  Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. The extent of atherosclerosis was expressed as percent atheroma volume (PAV) in a ≥ 40 mm segment of one targeted (imaged) coronary artery, calculated as the percentage of the total vessel volume occupied by atheroma. Regression in PAV was defined as any reduction from baseline in PAV.
• Percentage of Participants With Regression in Total Atheroma Volume [ Time Frame: Baseline and week 78 ]
  Intravascular ultrasound (IVUS) was used to visualize the extent of atherosclerotic plaques in the coronary artery lumen. Total atheroma volume (TAV) in a ≥ 40 mm segment of the targeted coronary artery was calculated as the average plaque area over the number of images that were evaluated by IVUS multiplied by the median vessel length to compensate for differences in segment length between participants. Regression in TAV was defined as any reduction from baseline in TAV.

Original Secondary Outcome Measures (submitted: March 15, 2013)

• Percentage of subjects demonstrating regression (any reduction from baseline) in PAV [ Time Frame: 78 weeks ]
• Nominal change in normalized total atheroma volume (TAV) from baseline to 78 weeks [ Time Frame: 78 weeks ]
• Percentage of subjects demonstrating regression (any reduction from baseline) in TAV [ Time Frame: 78 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound
• Official Title: A Double-blind, Randomized, Multi-center, Placebo-controlled, Parallel-group Study to Determine the Effects of Evolocumab (AMG 145) Treatment on Atherosclerotic Disease Burden as Measured by Intravascular Ultrasound in Subjects Undergoing Coronary Catheterization
• Brief Summary: This study will evaluate whether low-density lipoprotein (LDL-C) lowering with evolocumab (AMG 145) results in greater change from baseline in percent atheroma volume (PAV) at week 78 than placebo in adults with coronary artery disease taking lipid lowering therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypercholesterolemia

Intervention

• Biological: Evolocumab
  Administered by subcutaneous injection
  Other Names:

  • AMG 145
  • Repatha®
• Drug: Placebo
  Administered by subcutaneous injection

Study Arms

• Placebo Comparator: Placebo
  Participants received placebo to evolocumab administered by subcutaneous injection once a month for 76 weeks.
  Intervention: Drug: Placebo
• Experimental: Evolocumab
  Participants received 420 mg evolocumab administered by subcutaneous injection once a month for 76 weeks.
  Intervention: Biological: Evolocumab

Publications *

• Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016 Dec 13;316(22):2373-2384. doi: 10.1001/jama.2016.16951.
• Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJP, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Honda S, Shishikura D, Scherer DJ, Borgman M, Brennan DM, Wolski K, Nissen SE. Effect of Evolocumab on Coronary Plaque Composition. J Am Coll Cardiol. 2018 Oct 23;72(17):2012-2021. doi: 10.1016/j.jacc.2018.06.078.
• Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
• Puri R, Nissen SE, Somaratne R, Cho L, Kastelein JJ, Ballantyne CM, Koenig W, Anderson TJ, Yang J, Kassahun H, Wasserman SM, Scott R, Borgman M, Nicholls SJ. Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV). Am Heart J. 2016 Jun;176:83-92. doi: 10.1016/j.ahj.2016.01.019. Epub 2016 Feb 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 21, 2015): 970
• Original Estimated Enrollment (submitted: March 15, 2013): 950
• Actual Study Completion Date: July 29, 2016
• Actual Primary Completion Date: July 12, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Clinical indication for coronary angiography
• Subjects already taking statin therapy, niacin or ezetimibe at screening must have been on a stable dose for at least 4 weeks prior to screening LDL-C. Subjects not taking lipid-regulating therapy must enter the study via a lipid stabilization period. Subjects who are intolerant to statins must meet statin intolerance entry criteria
• Fasting LDL-C ≥ 80 mg/dL (2.07 mmol/L) with or without additional risk factors, or, LDL-C ≥ 60 -< 80 mg/dL (1.55-2.07 mmol/L) in the presence of one major or three minor risk factors

Subjects must meet the following criteria at the qualifying coronary catheterization procedure:

• Evidence of coronary heart disease (at least one lesion in a native coronary artery that has > 20% reduction in lumen diameter) or prior percutaneous intervention (PCI)
• Left main coronary artery < 50% reduction in lumen diameter by visual estimation
• Target coronary artery for IVUS must be accessible to the IVUS catheter, must not have a > 50% reduction in lumen diameter within the target segment (and at least 40 mm in length); cannot have undergone prior PCI or coronary artery bypass graft (CABG) and is not a candidate for intervention over the next 18 months. It may not be a bypass graft, bypassed vessel or culprit vessel for previous myocardial infarction (MI).

Exclusion Criteria:

• Coronary artery bypass graft surgery < 6 weeks prior to the qualifying IVUS
• New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction less than 30%
• Uncontrolled cardiac arrhythmia that is not controlled by medications in the 3 months prior to randomization
• Known hemorrhagic stroke
• Uncontrolled hypertension at randomization
• Fasting Triglycerides ≥ 400 mg/dL (4.5 mmol/L) at screening
• Type 1 diabetes or poorly controlled type 2 diabetes (hemoglobin A1c [HbA1c] > 9%) at screening.
• Moderate to severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73m²) at screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Philippines, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01813422
• Other Study ID Numbers: 20120153; 2012-004208-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: February 2019