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NCT01813422: GLAGOV

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

Completed Phase 3 Results posted Last updated 20 February 2019
What this trial tests

Phase 3 trial testing Evolocumab in Hypercholesterolemia in 970 participants. Completed in 29 July 2016.

Timeline
18 April 2013
Primary endpoint
12 July 2016
29 July 2016

Quick facts

Lead sponsorAmgen
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment970
Start date18 April 2013
Primary completion12 July 2016
Estimated completion29 July 2016
Sites226 locations across Italy, Malaysia, Taiwan, Ireland, Poland, South Korea, Philippines, Denmark

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 99, any sex, with Hypercholesterolemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Percent Atheroma Volume at Week 78 Primary · 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.

GroupValue95% CI
Placebo0.053± 0.189
Evolocumab-0.955± 0.190
Change From Baseline in Total Atheroma Volume at Week 78 Secondary · 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.

GroupValue95% CI
Placebo-0.910± 1.214
Evolocumab-5.799± 1.216
Percentage of Participants With Regression in Percent Atheroma Volume Secondary · 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.

GroupValue95% CI
Placebo47.342.6 – 52.0
Evolocumab64.359.6 – 68.7
Percentage of Participants With Regression in Total Atheroma Volume Secondary · 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.

GroupValue95% CI
Placebo48.944.2 – 53.7
Evolocumab61.556.7 – 66.0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug until week 80. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 142/484 (29%)
Deaths:
Evolocumab
Serious: 135/484 (28%)
Deaths:

Serious adverse events (213 terms)

ReactionSystemPlaceboEvolocumab
Angina pectorisCardiac disorders
Coronary artery diseaseCardiac disorders
Non-cardiac chest painGeneral disorders
Angina unstableCardiac disorders
Acute myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Arteriosclerosis coronary arteryCardiac disorders
Coronary artery stenosisCardiac disorders
PneumoniaInfections and infestations
Myocardial infarctionCardiac disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Acute coronary syndromeCardiac disorders
Coronary artery occlusionCardiac disorders
Myocardial ischaemiaCardiac disorders
Vascular stent restenosisGeneral disorders
Back painMusculoskeletal and connective tissue disorders
SyncopeNervous system disorders
DepressionPsychiatric disorders
NephrolithiasisRenal and urinary disorders
HypotensionVascular disorders
AnaemiaBlood and lymphatic system disorders
Cardiac failureCardiac disorders
Coronary artery dissectionCardiac disorders
Other adverse events (5 terms — click to expand)

ReactionSystemPlaceboEvolocumab
MyalgiaMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
Chest painGeneral disorders
Angina pectorisCardiac disorders
HeadacheNervous system disorders

Most-reported serious reactions: Angina pectoris, Coronary artery disease, Non-cardiac chest pain, Angina unstable, Acute myocardial infarction, Atrial fibrillation, Arteriosclerosis coronary artery, Coronary artery stenosis.

Data from ClinicalTrials.gov NCT01813422 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Pleiotropic Effects of Statins on the Cardiovascular System.
    Oesterle A, Laufs U, Liao JK. · · 2017 · cited 919× · PMID 28057795 · DOI 10.1161/circresaha.116.308537
  2. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial.
    Nicholls SJ, Puri R, Anderson T, Ballantyne CM, et al · · 2016 · cited 826× · PMID 27846344 · DOI 10.1001/jama.2016.16951
  3. PCSK9 inhibitors: A new era of lipid lowering therapy.
    Chaudhary R, Garg J, Shah N, Sumner A. · · 2017 · cited 199× · PMID 28289523 · DOI 10.4330/wjc.v9.i2.76
  4. Effect of Evolocumab on Coronary Plaque Composition.
    Nicholls SJ, Puri R, Anderson T, Ballantyne CM, et al · · 2018 · cited 111× · PMID 30336824 · DOI 10.1016/j.jacc.2018.06.078
  5. Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.
    Bao X, Liang Y, Chang H, Cai T, et al · · 2024 · cited 101× · PMID 38185721 · DOI 10.1038/s41392-023-01690-3
  6. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol.
    Poirier S, Mayer G. · · 2013 · cited 59× · PMID 24115837 · DOI 10.2147/dddt.s36984
  7. PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis.
    Wang X, Wen D, Chen Y, Ma L, et al · · 2022 · cited 50× · PMID 35706032 · DOI 10.1186/s12933-022-01542-4
  8. Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol.
    Toth PP, Bray S, Villa G, Palagashvili T, et al · · 2022 · cited 35× · PMID 36073669 · DOI 10.1161/jaha.122.025551

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01813422.

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