HyperlipidemiaPhase 1NCT01133522
Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Evolocumab (AMG 145) in Adults With Hyperlipidemia on Stable Doses of a Statin
A Phase 1 study testing Evolocumab in people with Hyperlipidemia, run by Amgen.
Trial summary
The purpose of the study is to evaluate the safety and tolerability of multiple doses of evolocumab when given as an add-on to stable statin therapy. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hyperlipidemia
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2010to 14 Sep 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ages 18 to 70 years (inclusive) at the time of screening with hyperlipidemia
- Body mass index (BMI) ≥18 and ≤ 35 kg/m^2 at the time of screening
- Low-density lipoprotein cholesterol (LDL-C) level of 70-220 mg/dL (inclusive) at screening as measured by direct assay
- For Cohorts 1-5: On a stable dose of rosuvastatin (Crestor) < 40 mg/day, atorvastatin (Lipitor) < 80 mg/day, or simvastatin (Zocor) 20-80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
- For Cohort 6: On a stable dose of rosuvastatin (Crestor) 40 mg/day or atorvastatin (Lipitor) 80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
- For Cohort 7: Diagnosis of heterozygous familial hypercholesterolemia, based on a score of ≥ 9 points using the World health Organization (WHO) criteria
Who cannot join
- Diagnosis of homozygous familial hypercholesterolemia
- History of heart failure, coronary artery bypass graft, or cardiac arrhythmia
- History of acute coronary syndrome (e.g. myocardial infarction, hospitalization for unstable angina) or percutaneous coronary intervention, within 12 months prior to enrollment
- Planned cardiac surgery or revascularization
- Known aortic, peripheral vascular or cerebrovascular disease (including history of stroke or transient ischemic attack)
- Diabetes mellitus with any of the following:
Show all 10Show fewer
- known microvascular or macrovascular disease
- HbA1c > 8.0% at screening
- use of any hypoglycemic medication other than metformin
- Uncontrolled hypertension (systolic blood pressure ≥ 150 or diastolic blood pressure ≥ 90 mmHg) either on or off therapy at screening or at baseline
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 145 in Subjects With Hyperlipidemia on Stable Doses of a Statin
The purpose of the study is to evaluate the safety and tolerability of multiple doses of evolocumab when given as an add-on to stable statin therapy.
Read the detailed description
Participants receiving low-to-moderate-dose statins were randomized in a 1:3 ratio to receive subcutaneous placebo or evolocumab and enrolled sequentially into one of 5 dose-escalation cohorts:
- Evolocumab 14 mg/placebo once weekly (QW) × 6 doses
- Evolocumab 35 mg/placebo once weekly (QW) × 6 doses
- Evolocumab 140 mg/placebo every 2 weeks (Q2W) × 3 doses
- Evolocumab 280 mg/placebo every 2 weeks (Q2W) × 3 doses
- Evolocumab 420 mg/placebo every 4 weeks (Q2W) × 2 doses.
Participants receiving high-dose statins were randomized 1:3 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 6).
Participants diagnosed with familial hypercholesterolemia (HeFH) were randomized 1:2 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 7).
- Conditions
- Hyperlipidemia
- Being tested
- Evolocumab, Placebo
- Keywords
- AMG145, Multiple Dose, Statin, Ascending
- Medical subject headings
- Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabBiological
Also called AMG 145, Repatha
Administered by subcutaneous injection
PlaceboBiological
Administered by subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab | Experimental | Participants received one of 5 dose levels of evolocumab administered as multiple subcutaneous doses. Receives: Biological: Evolocumab |
| Placebo | Placebo comparator | Participants received matching placebo dose regimens by subcutaneous injection. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
The relationship of each adverse event to the investigational product was assessed by the investigator.
A serious adverse event (SAE) is defined as an adverse event that
- is fatal
- is life threatening (places the subject at immediate risk of death)
- requires in-patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- is a congenital anomaly/birth defect
- other significant medical hazard.
Measured: From the first dose of study drug until Day 85
Number of Participants With Anti-Evolocumab Antibodies
Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies
Measured: From the first dose of study drug until Day 85
Secondary outcomes (4)
Maximum Observed Plasma Concentration (Cmax) of Evolocumab
Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 800 ng/mL.
Measured: Day 1, predose and Days 4, 8, 15, 22, 29, 36, 40, 43, 50, 57, 64, 71, 78, and 85
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Evolocumab
Area under the unbound evolocumab serum concentration-time curve from time of last dose to time of last quantifiable concentration following the last dose of evolocumab.
Measured: Day 29 predose (last dose for Cohorts 3-7) and Days 36 (predose for Cohorts 1 and 2), 40, 43, 50, 57, 64, 71, 78, and 85
Percent Change From Baseline to End of the Dosing Interval in LDL-C
Measured: Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group
Percent Change From Baseline to End of the Dosing Interval in PCSK9
Serum PCSK9 concentrations were determined by using a qualified enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 15 ng/mL.
Measured: Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2010 (estimated)
- Study start1 Jun 2010
- Primary completion14 Sep 2011
- Study completion14 Sep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperlipidemiaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01133522
- Sponsor's protocol ID
- 20080398
- Status last verified
- Nov 2018
- First submitted
- 27 May 2010
- Last updated
- 2 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Dias CS, Shaywitz AJ, Wasserman SM, Smith BP, Gao B, Stolman DS, Crispino CP, Smirnakis KV, Emery MG, Colbert A, Gibbs JP, Retter MW, Cooke BP, Uy ST, Matson M, Stein EA. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol. 2012 Nov 6;60(19):1888-98. doi: 10.1016/j.jacc.2012.08.986. Epub 2012 Oct 17.
PubMed 23083772
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 145 in Subjects With Hyperlipidemia on Stable Doses of a Statin
- ClinicalTrials.gov ID
- NCT01133522
- Acronym / sponsor ID
- 20080398
- Conditions
- Hyperlipidemia
- Keywords
- AMG145, Multiple Dose, Statin, Ascending
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2010 (actual)
- Primary completion
- 14 Sep 2011 (actual)
- Study completion
- 14 Sep 2011 (actual)
- First posted
- 31 May 2010 (estimated)
- Results
- Posted 22 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate the safety and tolerability of multiple doses of evolocumab when given as an add-on to stable statin therapy.
Detailed description
Participants receiving low-to-moderate-dose statins were randomized in a 1:3 ratio to receive subcutaneous placebo or evolocumab and enrolled sequentially into one of 5 dose-escalation cohorts:
- Evolocumab 14 mg/placebo once weekly (QW) × 6 doses
- Evolocumab 35 mg/placebo once weekly (QW) × 6 doses
- Evolocumab 140 mg/placebo every 2 weeks (Q2W) × 3 doses
- Evolocumab 280 mg/placebo every 2 weeks (Q2W) × 3 doses
- Evolocumab 420 mg/placebo every 4 weeks (Q2W) × 2 doses.
Participants receiving high-dose statins were randomized 1:3 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 6).
Participants diagnosed with familial hypercholesterolemia (HeFH) were randomized 1:2 to receive subcutaneous placebo or evolocumab 140 mg every 2 weeks × 3 doses (Cohort 7).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Evolocumab | Experimental | Biological: EvolocumabParticipants received one of 5 dose levels of evolocumab administered as multiple subcutaneous doses. |
| Placebo | Placebo comparator | Biological: PlaceboParticipants received matching placebo dose regimens by subcutaneous injection. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women ages 18 to 70 years (inclusive) at the time of screening with hyperlipidemia
- Body mass index (BMI) ≥18 and ≤ 35 kg/m^2 at the time of screening
- Low-density lipoprotein cholesterol (LDL-C) level of 70-220 mg/dL (inclusive) at screening as measured by direct assay
- For Cohorts 1-5: On a stable dose of rosuvastatin (Crestor) < 40 mg/day, atorvastatin (Lipitor) < 80 mg/day, or simvastatin (Zocor) 20-80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
- For Cohort 6: On a stable dose of rosuvastatin (Crestor) 40 mg/day or atorvastatin (Lipitor) 80 mg/day for ≥ 1 month prior to enrollment and expected to remain on this dose for the remainder of the study
Key exclusion criteria (10 listed)
- Diagnosis of homozygous familial hypercholesterolemia
- History of heart failure, coronary artery bypass graft, or cardiac arrhythmia
- History of acute coronary syndrome (e.g. myocardial infarction, hospitalization for unstable angina) or percutaneous coronary intervention, within 12 months prior to enrollment
- Planned cardiac surgery or revascularization
- Known aortic, peripheral vascular or cerebrovascular disease (including history of stroke or transient ischemic attack)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabAlso: AMG 145, RepathaAdministered by subcutaneous injection | Biological | Evolocumab |
| PlaceboAdministered by subcutaneous injection | Biological | Placebo |
Primary outcome
Number of Participants With Adverse Events
Time frame: From the first dose of study drug until Day 85
The relationship of each adverse event to the investigational product was assessed by the investigator. A serious adverse event (SAE) is defined as an adverse event that * is fatal * is life threatening (places the subject at immediate risk of death) * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * other significant medical hazard.
Number of Participants With Anti-Evolocumab Antibodies
Time frame: From the first dose of study drug until Day 85
Serum samples were analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-evolocumab binding antibodies. Positive samples were subsequently tested in a receptor-ligand binding bioassay for anti-evolocumab neutralizing antibodies
4 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) of Evolocumab
Time frame: Day 1, predose and Days 4, 8, 15, 22, 29, 36, 40, 43, 50, 57, 64, 71, 78, and 85
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Evolocumab
Time frame: Day 29 predose (last dose for Cohorts 3-7) and Days 36 (predose for Cohorts 1 and 2), 40, 43, 50, 57, 64, 71, 78, and 85
Percent Change From Baseline to End of the Dosing Interval in LDL-C
Time frame: Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group
Percent Change From Baseline to End of the Dosing Interval in PCSK9
Time frame: Baseline and Day 43 for QW and Q2W groups or Day 57 for Q4W group
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23083772Dias CS, Shaywitz AJ, Wasserman SM, Smith BP, Gao B, Stolman DS, Crispino CP, Smirnakis KV, Emery MG, Colbert A, Gibbs JP, Retter MW, Cooke BP, Uy ST, Matson M, Stein EA. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol. 2012 Nov 6;60(19):1888-98. doi: 10.1016/j.jacc.2012.08.986. Epub 2012 Oct 17.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Evolocumab in people with Hyperlipidemia, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: From the first dose of study drug until Day 85). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01133522, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2018.