NCT02833844

Safety, Tolerability and Efficacy on Low Density Lipoprotein Cholesterol (LDL-C) of Evolocumab in Participants With Human Immunodeficiency Virus (HIV) and Hyperlipidemia/Mixed Dyslipidemia

Completed Phase 3 Results posted Last updated 22 July 2022

What this trial tests

Phase 3 trial testing Evolocumab in Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection in 467 participants. Completed in 27 January 2020.

Timeline

22 May 2017

Primary endpoint
9 July 2019

27 January 2020

Quick facts

Lead sponsor	Amgen
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	467
Start date	22 May 2017
Primary completion	9 July 2019
Estimated completion	27 January 2020
Sites	78 locations across France, Italy, South Africa, Greece, Belgium, United Kingdom, Poland, Romania

Drugs / interventions tested

• Evolocumab (EVOLOCUMAB) — full drug profile →
• Placebo

Conditions studied

• Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection — all drugs for Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection →

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Subjects With Hyperlipidemia, Dyslipidemia and HIV Infection. 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.

Percent Change From Baseline in LDL-C at Week 24 Primary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	1.68	± 2.03
Double-Blind Evolocumab	-55.23	± 1.52

Change From Baseline in LDL-C at Week 24 Secondary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	-2.3	± 3.1
Double-Blind Evolocumab	-77.5	± 2.3

Percentage of Participants Acheiving LDL-C < 70 mg/dL (1.8 mmol/L) at Week 24 Secondary · Week 24

Group	Value	95% CI
Double-Blind Placebo	7.9	4.6 – 13.4
Double-Blind Evolocumab	73.3	68.0 – 78.0

Percentage of Participants With an LDL-C Response (50% Reduction of LDL-C From Baseline) at Week 24 Secondary · Baseline, Week 24

Group	Value	95% CI
Double-Blind Placebo	0.7	0.1 – 3.7
Double-Blind Evolocumab	72.5	67.2 – 77.3

Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (HDL-C) at Week 24 Secondary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	2.86	± 1.74
Double-Blind Evolocumab	-48.07	± 1.31

Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 24 Secondary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	2.59	± 1.50
Double-Blind Evolocumab	-45.14	± 1.13

Percent Change From Baseline in Total Cholesterol (TC) at Week 24 Secondary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	2.34	± 1.40
Double-Blind Evolocumab	-35.78	± 1.06

Percent Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 24 Secondary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	10.35	± 3.34
Double-Blind Evolocumab	-16.44	± 2.57

Percent Change From Baseline in Triglycerides at Week 24 Secondary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	13.21	± 3.80
Double-Blind Evolocumab	-9.25	± 2.89

Percent Change From Baseline in HDL-C at Week 24 Secondary · Bseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	2.73	± 1.57
Double-Blind Evolocumab	11.08	± 1.20

Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 24 Secondary · Baseline, Week 24

Least squares mean is from the repeated measures model which includes treatment group, statin stratification factor, scheduled visit and the interaction of treatment with scheduled visit as covariates. (Hepatitis C stratification factor is not included in the model due to low participant numbers.)

Group	Value	95% CI
Double-Blind Placebo	12.34	± 3.54
Double-Blind Evolocumab	-9.81	± 2.65

Adverse events — posted to ClinicalTrials.gov

Time frame: Double-blind Treatment (DBT) Period: From randomization (for all-cause mortality) or first dose of study drug (for adverse events) to up to week 24. Open-label Extension (OLE) Period: From the start of the OLE (week 24) to end of study (week 52) for all-cause mortality; and from first dose of study drug in the OLE up to 30 days after last dose, or end of study, whichever was earlier, for adverse events.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-Blind Placebo

Serious: 8/157 (5%)

Deaths: 0/157

Double-Blind Evolocumab

Serious: 10/307 (3%)

Deaths: 0/310

Double-Blind Placebo/Open-Label Evolocumab

Serious: 8/152 (5%)

Deaths: 0/152

Double-Blind Evolocumab/Open-Label Evolocumab

Serious: 14/299 (5%)

Deaths: 2/303

Serious adverse events (52 terms)

Reaction	System	Double-Blind Placebo	Double-Blind Evolocumab	Double-Blind Placebo/Open-…	Double-Blind Evolocumab/Op…
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Arteriosclerosis coronary artery	Cardiac disorders	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—
Coronary artery stenosis	Cardiac disorders	—	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—	—
Ventricular tachycardia	Cardiac disorders	—	—	—	—
Anal fistula	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—	—
Staphylococcal infection	Infections and infestations	—	—	—	—
Tracheobronchitis	Infections and infestations	—	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—
Diabetic ketoacidosis	Metabolism and nutrition disorders	—	—	—	—
Flank pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	—	—	—	—
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—
Subarachnoid haemorrhage	Nervous system disorders	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Hypertensive emergency	Vascular disorders	—	—	—	—

Other adverse events (15 terms — click to expand)

Reaction	System	Double-Blind Placebo	Double-Blind Evolocumab	Double-Blind Placebo/Open-…	Double-Blind Evolocumab/Op…
Influenza like illness	General disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—

Most-reported serious reactions: Osteoarthritis, Angina pectoris, Arteriosclerosis coronary artery, Atrial fibrillation, Cardiac failure congestive, Coronary artery stenosis, Myocardial ischaemia, Ventricular tachycardia.

Data from ClinicalTrials.gov NCT02833844 adverse events section.

Sponsor's own description

The study is divided into 2 parts. The first part of the study will be double-blinded and will last for 24 weeks. During this time, participants will be randomized in a ratio of 2:1 to receive either evolocumab once monthly (QM) or placebo QM. The second part of the study is a 24-week open label extension period. During this time all participants will receive evolocumab QM.

The clinical hypothesis is that subcutaneous evolocumab QM will be well tolerated and will result in greater reduction of low density lipoprotein cholesterol (LDL-C), defined as percent change from baseline at Week 24, compared with placebo QM in human immunodeficiency virus (HIV)-positive participants with hyperlipidemia or mixed dyslipidemia.

Publications & conference data

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

1. 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
2. Cardiovascular risk and dyslipidemia among persons living with HIV: a review.
   Maggi P, Di Biagio A, Rusconi S, Cicalini S, et al · · 2017 · cited 99× · PMID 28793863 · DOI 10.1186/s12879-017-2626-z
3. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.
   Schmidt AF, Pearce LS, Wilkins JT, Overington JP, et al · · 2017 · cited 78× · PMID 28453187 · DOI 10.1002/14651858.cd011748.pub2
4. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.
   Schmidt AF, Carter JL, Pearce LS, Wilkins JT, et al · · 2020 · cited 56× · PMID 33078867 · DOI 10.1002/14651858.cd011748.pub3
5. Evolocumab in HIV-Infected Patients With Dyslipidemia: Primary Results of the Randomized, Double-Blind BEIJERINCK Study.
   Boccara F, Kumar PN, Caramelli B, Calmy A, et al · · 2020 · cited 46× · PMID 32234462 · DOI 10.1016/j.jacc.2020.03.025
6. Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update.
   Kaddoura R, Orabi B, Salam AM. · · 2020 · cited 18× · PMID 32939318 · DOI 10.1080/21556660.2020.1801452
7. Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period.
   Boccara F, Caramelli B, Calmy A, Kumar P, et al · · 2022 · cited 12× · PMID 35025817 · DOI 10.1097/qad.0000000000003175