NCT01854918: OSLER-2

Open-label Extension Study of Evolocumab (AMG 145) in Adults With Hyperlipidemia and Mixed Dyslipidemia

Completed Phase 3 Results posted Last updated 11 June 2019

What this trial tests

Phase 3 trial testing Evolocumab in Hyperlipidemia and Mixed Dyslipidemia in 3,681 participants. Completed in 31 May 2018.

Timeline

23 April 2013

Primary endpoint
31 May 2018

31 May 2018

Quick facts

Lead sponsor	Amgen
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	3,681
Start date	23 April 2013
Primary completion	31 May 2018
Estimated completion	31 May 2018
Sites	363 locations across Hong Kong, Italy, Japan, Taiwan, Poland, South Korea, Denmark, New Zealand

Drugs / interventions tested

• Evolocumab (EVOLOCUMAB) — full drug profile →
• Standard of Care

Conditions studied

• Hyperlipidemia and Mixed Dyslipidemia — all drugs for Hyperlipidemia and Mixed Dyslipidemia →

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 85, any sex, with Hyperlipidemia and Mixed Dyslipidemia. 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.

Number of Participants With Adverse Events Primary · 48 weeks in the SOC-controlled period and up to 2 years in the All-IP period

Adverse event (AE) severity assessments were made using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading, version 4.0, where grade 1 = mild AE, grade 2 = moderate AE, Grade 3 = severe AE, grade 4 = life-threatening AE and Grade 5 = death due to AE.

All adverse events

Group	Value	95% CI
Year 1: Standard of Care	796
Year 1: Evolocumab + Standard of Care	1655
Years 2-3: SOC / Evolocumab + SOC	929
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	1789

Adverse events ≥ grade 2

Group	Value	95% CI
Year 1: Standard of Care	519
Year 1: Evolocumab + Standard of Care	1070
Years 2-3: SOC / Evolocumab + SOC	700
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	1339

Adverse events ≥ grade 3

Group	Value	95% CI
Year 1: Standard of Care	124
Year 1: Evolocumab + Standard of Care	225
Years 2-3: SOC / Evolocumab + SOC	214
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	379

Adverse events ≥ grade 4

Group	Value	95% CI
Year 1: Standard of Care	7
Year 1: Evolocumab + Standard of Care	17
Years 2-3: SOC / Evolocumab + SOC	11
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	35

Serious adverse events

Group	Value	95% CI
Year 1: Standard of Care	104
Year 1: Evolocumab + Standard of Care	195
Years 2-3: SOC / Evolocumab + SOC	178
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	332

AEs leading to discontinuation of evolocumab

Group	Value	95% CI
Year 1: Standard of Care	0
Year 1: Evolocumab + Standard of Care	55
Years 2-3: SOC / Evolocumab + SOC	26
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	42

Fatal adverse events

Group	Value	95% CI
Year 1: Standard of Care	5
Year 1: Evolocumab + Standard of Care	5
Years 2-3: SOC / Evolocumab + SOC	3
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	16

Device related adverse events

Group	Value	95% CI
Year 1: Standard of Care	0
Year 1: Evolocumab + Standard of Care	57
Years 2-3: SOC / Evolocumab + SOC	25
Years 2-3: Evolocumab + SOC / Evolocumab + SOC	45

Percent Change From Baseline in LDL-C at Weeks 48 and 104 Secondary · Baseline of the parent study and weeks 48 amd 104

Week 48

Group	Value	95% CI
Standard of Care	7.43	± 38.93
Evolocumab + Standard of Care	-51.59	± 28.88

Week 104

Group	Value	95% CI
Standard of Care	-49.96	± 33.29
Evolocumab + Standard of Care	-50.31	± 30.34

Change From Baseline in LDL-C at Weeks 48 and 104 Secondary · Baseline of the parent study and weeks 48 amd 104

Week 48

Group	Value	95% CI
Standard of Care	0.4	± 43.9
Evolocumab + Standard of Care	-68.8	± 46.6

Week 104

Group	Value	95% CI
Standard of Care	-66.4	± 50.1
Evolocumab + Standard of Care	-67.2	± 46.6

Adverse events — posted to ClinicalTrials.gov

Time frame: 48 weeks in the SOC-controlled period and up to 2 years in the All-IP period.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Year 1: Standard of Care

Serious: 104/1227 (8%)

Deaths: 5/1227

Year 1: Evolocumab + Standard of Care

Serious: 195/2454 (8%)

Deaths: 5/2454

Years 2-3: SOC / Evolocumab + SOC

Serious: 181/1197 (15%)

Deaths: 5/1197

Years 2-3: Evolocumab + SOC / Evolocumab + SOC

Serious: 344/2391 (14%)

Deaths: 16/2391

Years 2-3: Total

Serious: 525/3588 (15%)

Deaths: 21/3588

Serious adverse events (497 terms)

Reaction	System	Year 1: Standard of Care	Year 1: Evolocumab + Stand…	Years 2-3: SOC / Evolocuma…	Years 2-3: Evolocumab + SO…	Years 2-3: Total
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—
Angina unstable	Cardiac disorders	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—	—
Transient ischaemic attack	Nervous system disorders	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—
Diverticulitis	Infections and infestations	—	—	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—	—
Inguinal hernia	Gastrointestinal disorders	—	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Year 1: Standard of Care	Year 1: Evolocumab + Stand…	Years 2-3: SOC / Evolocuma…	Years 2-3: Evolocumab + SO…	Years 2-3: Total
Nasopharyngitis	Infections and infestations	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—

Most-reported serious reactions: Osteoarthritis, Angina pectoris, Non-cardiac chest pain, Pneumonia, Acute myocardial infarction, Angina unstable, Atrial fibrillation, Intervertebral disc protrusion.

Data from ClinicalTrials.gov NCT01854918 adverse events section.

Sponsor's own description

This study will contribute to the evaluation of long-term safety, tolerability and efficacy of evolocumab (AMG 145) in adults with hyperlipidemia and adults with mixed dyslipidemia.

Publications & conference data

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

1. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events.
   Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, et al · · 2015 · cited 1125× · PMID 25773607 · DOI 10.1056/nejmoa1500858
2. 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
3. Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study.
   Kastelein JJ, Nissen SE, Rader DJ, Hovingh GK, et al · · 2016 · cited 56× · PMID 26757788 · DOI 10.1093/eurheartj/ehv707
4. PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database.
   di Mauro G, Zinzi A, Scavone C, Mascolo A, et al · · 2021 · cited 32× · PMID 33351170 · DOI 10.1007/s40264-020-01021-3
5. Comparison of PCSK9 Inhibitor Evolocumab vs Ezetimibe in Statin-Intolerant Patients: Design of the Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 3 (GAUSS-3) Trial.
   Nissen SE, Dent-Acosta RE, Rosenson RS, Stroes E, et al · · 2016 · cited 32× · PMID 26946077 · DOI 10.1002/clc.22518
6. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies.
   Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, et al · · 2020 · cited 28× · PMID 32114889 · DOI 10.1161/jaha.119.014129
7. PCSK9 inhibitors in the prevention of cardiovascular disease.
   Latimer J, Batty JA, Neely RD, Kunadian V. · · 2016 · cited 28× · PMID 27095708 · DOI 10.1007/s11239-016-1364-1
8. What Lessons Have We Learned and What Remains to be Clarified for PCSK9 Inhibitors? A Review of FOURIER and ODYSSEY Outcomes Trials.
   Furtado RHM, Giugliano RP. · · 2020 · cited 21× · PMID 32026310 · DOI 10.1007/s40119-020-00163-w