Subjects With Hyperlipidemia, DyslipidemiaPhase 3ANITSCHKOWNCT02729025
Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation in Patients With Elevated Lipoprotein(a) (Lp(a))
A Phase 3 study testing Evolocumab in people with Subjects With Hyperlipidemia, Dyslipidemia, run by Amgen at 15 sites in 3 countries.
Trial summary
A study to assess the effects of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibition on the arterial wall inflammation in patients with elevated lipoprotein(a). Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Subjects With Hyperlipidemia, Dyslipidemia
- 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
- 129 participants
- Where
- 15 sitesin 3 countries
- Study dates
- 14 Apr 2016to 5 Apr 2018
- Phase
- Phase 3
- 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 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fasting lipoprotein(a) (Lp(a)) 50 mg/dL or more at screening 1
- Fasting Low-density lipoprotein-cholesterol (LDL-C) 100 mg/dL or more at screening 1
- Lipid lowering therapy including statin dose unchanged for at least 8 weeks prior to screening
- Target-to-background ratio (TBR) maximum higher than 1.6 (either right, left carotid or thoracic aorta) on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT).
Who cannot join
- Currently receiving, or less than 4 weeks since receiving, treatment in another investigational device or drug study(ies), or participating in other investigational procedures
- Known diagnosis of diabetes mellitus or screening fasting serum glucose ≥ 126 mg/dL or hemoglobin A1C (HbA1C) ≥ 6.5%
- Subject with a history of homozygous familial hypercholesterolemia
- History of a Cardiovascular event
- Subject currently undergoing lipid apheresis
- Known contraindications or limitations to FDG-PET/ CT (scanner weight limit, devices that can cause image artifacts, or carotid/aortic stents/grafts
- Subject has had exposure to investigational drugs targeting Lp(a) within the last 12 months, prior to Screening
- Other Exclusion Criteria May Apply.
Trial locations and contacts
15 sites in 3 countries.
15 sites in 3 countries
Netherlands6 sites
Research Site
Amsterdam, 1105 AZ
Research Site
Apeldoorn, 7334 DZ
Research Site
Nijmegen, 6525 GA
Research Site
Rotterdam, 3015 CE
Research Site
Venlo, 5912 BL
Research Site
Waalwijk, 5141 BM
United States5 sites
Research Site
Hurst, Texas, 76054
Research Site
Las Vegas, Nevada, 89118
Research Site
Miami, Florida, 33144
Research Site
Mooresville, North Carolina, 28117
Research Site
Philadelphia, Pennsylvania, 19141
Canada4 sites
Research Site
Chicoutimi, Quebec, G7H 7K9
Research Site
Newmarket, Ontario, L3Y 5G8
Research Site
Québec, Quebec, G1V 4W2
Research Site
Toronto, Ontario, M9V 4B4
About this study
Official title: A RaNdomized Double-blInd Placebo ConTrolled Study Characterizing THe Effects of PCSK9 Inhibition On Arterial Wall Inflammation in Patients With Elevated Lp(a) (ANITSCHKOW)
A study to assess the effects of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibition on the arterial wall inflammation in patients with elevated lipoprotein(a).
- Being tested
- Evolocumab, Placebo
- Keywords
- Hyperlipidemia, Dyslipidemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition, Arterial Wall Inflamation, Elevated lipoprotein a
- Medical subject headings
- Dyslipidemias, Hyperlipidemias, Hypercholesterolemia, Autosomal Dominant, 3, Inhibition, Psychological
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called Repatha, AMG 145
Administered subcutaneously once a month using an autoinjector/pen.
PlaceboDrug
Administered subcutaneously once a month using an autoinjector/pen.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks. Receives: Drug: Placebo |
| Evolocumab 420 mg QM | Experimental | Participants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks. Receives: Drug: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16
Arterial inflammation was assessed using 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Arterial 18F-FDG uptake is correlated with arterial macrophage content and predicts cardiovascular events. Images were analyzed by an experienced radiologist blinded to all patient characteristics.
The maximum standardized uptake value was calculated as a time- and dose- corrected tissue radioactivity divided by body weight in the index and the target-to-background ratio (TBR) was calculated from the ratio of the standardized uptake value of the artery compared to mean background venous activity. The average maximum TBR for the most diseased segment (MDS) was calculated from a group of 3 contiguous slices (approximately 1.5 cm), centered on the slice with the highest maximum TBR in the index vessel. The index vessel was defined as the vessel (either the right or left carotid or aorta) with the highest mean TBR at baseline.
Measured: Baseline and week 16
Secondary outcomes (3)
Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16
Measured: Baseline and week 16
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16
Measured: Baseline and week 16
Percent Change From Baseline in Apolipoprotein B Concentration at Week 16
Measured: Baseline and week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study start14 Apr 2016
- Primary completion5 Apr 2018
- Study completion5 Apr 2018
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 (4)Papers the sponsor has linked to this study.
- Other trials for Subjects With Hyperlipidemia, DyslipidemiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 129 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
- NCT02729025
- Sponsor's protocol ID
- 20130293
- Other IDs
- 2015-003731-35, 2015
- Acronym
- ANITSCHKOW
- Status last verified
- Sep 2022
- First submitted
- 8 Mar 2016
- Last updated
- 23 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Stiekema LCA, Stroes ESG, Verweij SL, Kassahun H, Chen L, Wasserman SM, Sabatine MS, Mani V, Fayad ZA. Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment. Eur Heart J. 2019 Sep 1;40(33):2775-2781. doi: 10.1093/eurheartj/ehy862.
PubMed 30561610Schmidt 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.
PubMed 33078867Zhang X, Stiekema LCA, Stroes ESG, Groen AK. Metabolic effects of PCSK9 inhibition with Evolocumab in subjects with elevated Lp(a). Lipids Health Dis. 2020 May 11;19(1):91. doi: 10.1186/s12944-020-01280-0.
PubMed 32393252Stiekema LCA, Prange KHM, Hoogeveen RM, Verweij SL, Kroon J, Schnitzler JG, Dzobo KE, Cupido AJ, Tsimikas S, Stroes ESG, de Winther MPJ, Bahjat M. Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a). Eur Heart J. 2020 Jun 21;41(24):2262-2271. doi: 10.1093/eurheartj/ehaa171.
PubMed 32268367
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A RaNdomized Double-blInd Placebo ConTrolled Study Characterizing THe Effects of PCSK9 Inhibition On Arterial Wall Inflammation in Patients With Elevated Lp(a) (ANITSCHKOW)
- ClinicalTrials.gov ID
- NCT02729025
- Acronym / sponsor ID
- ANITSCHKOW / 20130293
- Keywords
- Hyperlipidemia, Dyslipidemia, Proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibition, Arterial Wall Inflamation, Elevated lipoprotein a
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 14 Apr 2016 (actual)
- Primary completion
- 5 Apr 2018 (actual)
- Study completion
- 5 Apr 2018 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Posted 23 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to assess the effects of proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibition on the arterial wall inflammation in patients with elevated lipoprotein(a).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo to evolocumab by subcutaneous injection once a month (QM) for 12 weeks. |
| Evolocumab 420 mg QM | Experimental | Drug: EvolocumabParticipants received 420 mg evolocumab by subcutaneous injection once a month (QM) for 12 weeks. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Fasting lipoprotein(a) (Lp(a)) 50 mg/dL or more at screening 1
- Fasting Low-density lipoprotein-cholesterol (LDL-C) 100 mg/dL or more at screening 1
- Lipid lowering therapy including statin dose unchanged for at least 8 weeks prior to screening
- Target-to-background ratio (TBR) maximum higher than 1.6 (either right, left carotid or thoracic aorta) on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT).
Key exclusion criteria (8 listed)
- Currently receiving, or less than 4 weeks since receiving, treatment in another investigational device or drug study(ies), or participating in other investigational procedures
- Known diagnosis of diabetes mellitus or screening fasting serum glucose ≥ 126 mg/dL or hemoglobin A1C (HbA1C) ≥ 6.5%
- Subject with a history of homozygous familial hypercholesterolemia
- History of a Cardiovascular event
- Subject currently undergoing lipid apheresis
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: Repatha, AMG 145Administered subcutaneously once a month using an autoinjector/pen. | Drug | Evolocumab 420 mg QM |
| PlaceboAdministered subcutaneously once a month using an autoinjector/pen. | Drug | Placebo |
Primary outcome
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16
Time frame: Baseline and week 16
Arterial inflammation was assessed using 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Arterial 18F-FDG uptake is correlated with arterial macrophage content and predicts cardiovascular events. Images were analyzed by an experienced radiologist blinded to all patient characteristics. The maximum standardized uptake value was calculated as a time- and dose- corrected tissue radioactivity divided by body weight in the index and the target-to-background ratio (TBR) was calculated from the ratio of the standardized uptake value of the artery compared to mean background venous activity. The average maximum TBR for the most diseased segment (MDS) was calculated from a group of 3 contiguous slices (approximately 1.5 cm), centered on the slice with the highest maximum TBR in the index vessel. The index vessel was defined as the vessel (either the right or left carotid or aorta) with the highest mean TBR at baseline.
3 secondary outcomes
Percent Change From Baseline in Lipoprotein(a) Concentration at Week 16
Time frame: Baseline and week 16
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration at Week 16
Time frame: Baseline and week 16
Percent Change From Baseline in Apolipoprotein B Concentration at Week 16
Time frame: Baseline and week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30561610Stiekema LCA, Stroes ESG, Verweij SL, Kassahun H, Chen L, Wasserman SM, Sabatine MS, Mani V, Fayad ZA. Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment. Eur Heart J. 2019 Sep 1;40(33):2775-2781. doi: 10.1093/eurheartj/ehy862.
- Derived from this study: PubMed 33078867Schmidt 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.
- Derived from this study: PubMed 32393252Zhang X, Stiekema LCA, Stroes ESG, Groen AK. Metabolic effects of PCSK9 inhibition with Evolocumab in subjects with elevated Lp(a). Lipids Health Dis. 2020 May 11;19(1):91. doi: 10.1186/s12944-020-01280-0.
- Derived from this study: PubMed 32268367Stiekema LCA, Prange KHM, Hoogeveen RM, Verweij SL, Kroon J, Schnitzler JG, Dzobo KE, Cupido AJ, Tsimikas S, Stroes ESG, de Winther MPJ, Bahjat M. Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a). Eur Heart J. 2020 Jun 21;41(24):2262-2271. doi: 10.1093/eurheartj/ehaa171.
- 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
15 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Evolocumab in people with Subjects With Hyperlipidemia, Dyslipidemia, run by Amgen at 15 sites in 3 countries.
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 4 inclusion and 8 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 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Netherlands, United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 23 Apr 2019). 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?
Percent Change From Baseline in Maximum Target-to-background Ratio in the Most Diseased Segment of the Index Vessel at Week 16 (time frame: Baseline and week 16). 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 NCT02729025, which also lists 4 linked publications.
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 23 Sep 2022.