HypercholesterolemiaPhase 2NCT01812707
Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan
A Phase 2 study testing Alirocumab and Atorvastatin in people with Hypercholesterolemia, run by Sanofi at 4 sites in Japan.
Trial summary
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9). Primary Objective of the study: To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in… Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- Alirocumab and Atorvastatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 4 sitesJapan
- Study dates
- Mar 2013to Jan 2014
- Phase
- Phase 2
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit.
- OR
- Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy.
Who cannot join
- LDL-C <100 mg/dL (<2.59 mmol/L)
- at screening visit for participants who were being treated with stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening OR
- at the end of the 6-week run-in period on atorvastatin for participants receiving a lipid lowering treatment other than atorvastatin, or not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening
- Participants with type 1 diabetes
- Participants with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening.
- The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
4 sites in 1 country.
Japan4 sites
Investigational Site Number 392002
Koganeishi
Investigational Site Number 392001
Shinjuku-Ku
Investigational Site Number 392003
Suita-Shi
Investigational Site Number 392004
Suita-Shi
About this study
Official title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Evaluating the Efficacy and Safety of Three Doses of SAR236553 (REGN727) Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥100 mg/dL (≥2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).
Primary Objective of the study:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥100 mg/dL (≥2.59 mmol/L) on ongoing stable atorvastatin therapy.
Secondary Objectives:
- To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
- To evaluate the safety and tolerability of alirocumab
- To evaluate the development of anti-alirocumab antibodies
- To evaluate the pharmacokinetics of alirocumab
Read the detailed description
The duration of study participation depended on the status of the participant at screening: 21 to 27 weeks including a screening/run-in period of 1 to 7 weeks, a double-blind treatment period of 12 weeks, followed by an 8-week follow-up period.
- Conditions
- Hypercholesterolemia
- Being tested
- Alirocumab, Placebo (for alirocumab), Atorvastatin
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
Also called SAR236553, RGEN727
Two SC injections in the abdomen only
Placebo (for alirocumab)Drug
Two subcutaneous (SC) injections in the abdomen only
Route of administration: subcutaneous injection (1 mL) in the abdomen
AtorvastatinDrug
Orally once daily at a stable dose of 5 to 20 mg as background therapy
Route of administration: oral administration in the evening
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Placebo (for alirocumab); Drug: Atorvastatin |
| Alirocumab 50 mg Q2W | Experimental | Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Atorvastatin |
| Alirocumab 75 mg Q2W | Experimental | Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Atorvastatin |
| Alirocumab 150 mg Q2W | Placebo comparator | Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.
Measured: Baseline to Week 12 (LOCF)
Secondary outcomes (6)
Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Measured: Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Measured: Baseline to Week 12 (LOCF)
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis
Measured: Week 12 (LOCF)
Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Measured: Baseline to Week 12 (LOCF)
Percent Change From Baseline in Fasting Triglycerides and Lipoprotein (a) at Week 12 - On-Treatment Analysis
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).
Measured: Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis
Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.
Measured: From Baseline to Week 12 (LOCF)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2013 (estimated)
- Study startMar 2013
- Primary completionJan 2014
- Study completionJan 2014
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 (2)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by SanofiThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01812707
- Sponsor's protocol ID
- DFI12361
- Other IDs
- U1111-1134-4749
- Status last verified
- Aug 2015
- First submitted
- 14 Mar 2013
- Last updated
- 4 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara-Dinet MT. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016 Jul 1;118(1):56-63. doi: 10.1016/j.amjcard.2016.04.011. Epub 2016 Apr 21.
PubMed 27184170Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
PubMed 30183102
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Evaluating the Efficacy and Safety of Three Doses of SAR236553 (REGN727) Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥100 mg/dL (≥2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy
- ClinicalTrials.gov ID
- NCT01812707
- Acronym / sponsor ID
- DFI12361
- Conditions
- Hypercholesterolemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Mar 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 18 Mar 2013 (estimated)
- Results
- Posted 24 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).
Primary Objective of the study:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥100 mg/dL (≥2.59 mmol/L) on ongoing stable atorvastatin therapy.
Secondary Objectives:
- To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
- To evaluate the safety and tolerability of alirocumab
- To evaluate the development of anti-alirocumab antibodies
- To evaluate the pharmacokinetics of alirocumab
Detailed description
The duration of study participation depended on the status of the participant at screening: 21 to 27 weeks including a screening/run-in period of 1 to 7 weeks, a double-blind treatment period of 12 weeks, followed by an 8-week follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo (for alirocumab), Drug: AtorvastatinPlacebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose. |
| Alirocumab 50 mg Q2W | Experimental | Drug: Alirocumab, Drug: AtorvastatinAlirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Alirocumab 75 mg Q2W | Experimental | Drug: Alirocumab, Drug: AtorvastatinAlirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Alirocumab 150 mg Q2W | Placebo comparator | Drug: Alirocumab, Drug: AtorvastatinAlirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit.
- OR
- Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy.
Key exclusion criteria (6 listed)
- LDL-C <100 mg/dL (<2.59 mmol/L)
- Participants with type 1 diabetes
- Participants with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening.
- The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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 |
|---|---|---|
| AlirocumabAlso: SAR236553, RGEN727Two SC injections in the abdomen only | Drug | Alirocumab 150 mg Q2W, Alirocumab 50 mg Q2W, Alirocumab 75 mg Q2W |
| Placebo (for alirocumab)Two subcutaneous (SC) injections in the abdomen only Route of administration: subcutaneous injection (1 mL) in the abdomen | Drug | Placebo |
| AtorvastatinOrally once daily at a stable dose of 5 to 20 mg as background therapy Route of administration: oral administration in the evening | Drug | Alirocumab 150 mg Q2W, Alirocumab 50 mg Q2W, Alirocumab 75 mg Q2W, Placebo |
Primary outcome
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.
6 secondary outcomes
Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis
Time frame: Week 12 (LOCF)
Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Percent Change From Baseline in Fasting Triglycerides and Lipoprotein (a) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis
Time frame: From Baseline to Week 12 (LOCF)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27184170Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara-Dinet MT. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016 Jul 1;118(1):56-63. doi: 10.1016/j.amjcard.2016.04.011. Epub 2016 Apr 21.
- Derived from this study: PubMed 30183102Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
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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.
Clinical Sciences & Operations study director
Sanofi
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alirocumab and Atorvastatin in people with Hypercholesterolemia, run by Sanofi at 4 sites in Japan.
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 3 inclusion and 6 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 4 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Sep 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?
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis (time frame: Baseline to Week 12 (LOCF)). 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 NCT01812707, which also lists 2 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 4 Oct 2016.