Microvascular Coronary Artery DiseasePhase 2NCT03236311
A Dose Titration Study to Assess the Effects of SAR407899 in Patients With MVA and/or Persistent Stable Angina Despite Angiographically Successful PCI
A Phase 2 study testing SAR407899, Adenosine and Regadenoson in people with Microvascular Coronary Artery Disease, run by Sanofi at 10 sites in 5 countries.
Trial summary
Primary Objective: To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in participants with microvascular angina (MVA) and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Microvascular Coronary Artery Disease
- What is being tested?
- SAR407899, Adenosine and Regadenoson
- 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
- 10 participants
- Where
- 10 sitesin 5 countries
- Study dates
- 12 Oct 2017to 23 Jul 2018
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants not at childbearing potential >=18 year-old or legal age of majority.
- Female participant if she has undergone sterilization at least 3 months earlier or was post-menopausal.
- Post-menopausal status was defined by having no menses for 12 months without an alternative medical cause.
- In females not treated with hormonal replacement therapy (HRT), menopausal status was confirmed by a high follicle stimulating hormone (FSH) level greater than 40 international units per litre (IU/L).
- In females on HRT and whose menopausal status was in doubt (i.e. in women aged less than 45 years), a highly effective contraception methods was required. Contraception was used during the whole study and for at least seven days corresponding to time needed to eliminate study treatment.
- Symptomatic stable angina pectoris (typical or atypical symptoms with an average of at least bi-weekly episodes over the past month).
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- Participants with non-obstructive (<50% stenosis) coronary arteries or intermediate stenosis (between 50 and 70%) should have fractional flow reserve (FFR) >0.80 or instantaneous wave-free ratio (iFR) >0.89 on angiogram, documented within the previous 24 months*. In participants with stenting, a minimum diameter stenosis of <10% is required.
- or Coronary computed tomography angiography (CCTA) with finding of non-obstructive coronary arteries within the past 24 months in participants without previous percutaneous coronary intervention (PCI).
- Note: in cases of clinically suspected progression of atherosclerosis as per the Investigator, a more contemporary (i.e., 6 months) evidence should be provided.
- or CCTA performed during screening period, with finding of non-obstructive coronary arteries, in participants diagnosed with microvascular angina (MVA) and stable angina without previous PCI who did not have a coronary angiogram or CCTA in the previous 24 months but between 24 months to 5 years.
- Baseline global coronary flow reserve (CFR) (measured during the study) assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan <2.0.
Who cannot join
- Any use of nitrates (except short-acting nitrates) and/or dipyridamole and/or phosphodiesterase type 5 (PDE 5) inhibitors within one week prior to baseline PET scan or anticipated to be used during the study.
- Esophageal dysmotility or esophagitis.
- Participants with acute coronary syndrome (ACS) (myocardial infarction [MI] and/or unstable angina) in previous 3 months.
- Unsuccessful or incomplete coronary revascularization with residual obstructive stenosis or coronary artery disease (CAD) progression in native vessels as documented on invasive coronary angiography (>=50% stenosis) within 24 months of enrollment.
- Percutaneous coronary intervention performed at the time of an ACS (MI or unstable angina) in the previous 12 months.
- Recent PCI within the past 3 months.
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- Participants with history of coronary artery bypass grafting (CABG).
- Recent (<=3 months) major surgery (i.e. valvular surgery, surgery for congenital heart disease), stroke, transient ischemic attack [TIA], sustained ventricular arrhythmia, clinically significant structural heart disease (moderate-severe valvular disease, hypertrophic cardiomyopathy, congenital heart disease, pulmonary hypertension).
- Regional local flow abnormal perfusion defects at baseline PET scan*.
- Note: if contemporary evidence with invasive coronary angiography or CCTA demonstrates non-obstructive coronary arteries or if the regional local flow abnormal perfusion defect on PET scan is consistent with previous studies then participant qualifies for the study.
- Participants with cardiac conduction abnormalities (second or third degree atrioventricular [AV] block, sick sinus syndrome, symptomatic bradycardia, sinus node disease) except in participants fitted with a functioning pacemaker.
- History or known carotid stenosis:
- Carotid stenosis (>50%) or
- History of carotid stenosis in participants with previous symptoms.
- Contraindication or known hypersensitivity to adenosine or regadenoson.
- Contraindication to aminophylline.
- Contraindication to vasodilator stress PET scan and/or CCTA if CCTA needed during screening.
- Inability to discontinue treatment with methylxanthines treatment within 24 hours prior to PET scan.
- Participant unable to read, understand and fill a questionnaire without any help (eg, partially visually impaired or blind).
- Systolic blood pressure (SBP) <110 millimeter of mercury (mmHg) at baseline.
- Presence at baseline of symptomatic orthostatic hypotension (SBP decrease of 20 mmHg or more at Minute 3 or Minute 5 between seated and standing position), or asymptomatic orthostatic hypotension with a decrease in SBP equal or greater than 30 mmHg at Minute 3 or Minute 5 when changing from the seated to the standing position.
- Renal impairment with estimated glomerular filtration rate (eGFR) <50 milliliter/minute/1.73 square meter (mL/min/1.73 m^2) at screening and baseline.
- Drug-induced liver injury related criteria:
- Underlying hepatobiliary disease.
- Alanine Aminotransferase (ALT) >3 times the upper limit of normal (ULN).
- 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
10 sites in 5 countries.
10 sites in 5 countries
United States6 sites
Investigational Site Number 8400008
Baltimore, Maryland, 21287
Investigational Site Number 8400006
Boston, Massachusetts, 02115
Investigational Site Number 8400001
Jacksonville, Florida, 32209
Investigational Site Number 8400003
Los Angeles, California, 90048
Investigational Site Number 8400010
Philadelphia, Pennsylvania, 19104
Investigational Site Number 8400013
Wellington, Florida, 33449
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Parallel Arm Dose Titration Study to Assess the Effects of SAR407899 in Patients With Microvascular Angina (MVA) and/or Persistent Stable Angina Despite Angiographically Successful Percutaneous Coronary Intervention (PCI)
Primary Objective:
To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in participants with microvascular angina (MVA) and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI).
Read more
Secondary Objectives:
- To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire physical limitation scale (SAQ-PL) in participants with MVA and/or persistent stable angina despite angiographically successful PCI.
- To assess the safety of SAR407899 in participants with MVA and/or persistent stable angina despite angiographically successful PCI with a focus on identified risks such as hypotension and orthostatic hypotension.
- To assess SAR407899 plasma concentrations in MVA participants and/or persistent stable angina despite angiographically successful PCI.
Read the detailed description
The total duration of study per participant was:
- up to 9 weeks for participants with previous coronary artery angiography or coronary computed tomography angiography (CCTA) within 24 months prior to screening with up to 4 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration. or
- up to 11 weeks for participants with previous coronary artery angiography or CCTA between 24 months and 5 years prior to screening who need CCTA during screening period with up to 6 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration.
- Conditions
- Microvascular Coronary Artery Disease
- Being tested
- SAR407899, Placebo, Adenosine, Regadenoson, 13N-ammonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR407899Drug
Pharmaceutical form: Capsule Route of administration: Oral
PlaceboDrug
Pharmaceutical form: Capsule Route of administration: Oral
AdenosineDrug
Pharmaceutical form: Solution for injection Route of administration: Intravenous
RegadenosonDrug
Pharmaceutical form: Solution for injection Route of administration: Intravenous
13N-ammoniaDrug
Pharmaceutical form: Solution for injection Route of administration: Intravenous
82RubidiumDrug
Pharmaceutical form: Solution for injection Route of administration: Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching placebo for 4 weeks. Receives: Drug: Placebo; Drug: Adenosine; Drug: Regadenoson; Drug: 13N-ammonia; Drug: 82Rubidium |
| SAR407899 | Experimental | SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase). Receives: Drug: SAR407899; Drug: Adenosine; Drug: Regadenoson; Drug: 13N-ammonia; Drug: 82Rubidium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4
Absolute change from baseline to Week 4 in uncorrected global CFR, as assessed by the central core laboratory. The global CFR is the ratio of absolute myocardial blood flow (MBF) at stress over that at rest. The MBF was assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.
Measured: Baseline, Week 4
Secondary outcomes (2)
Change From Baseline in Angina-induced Physical Limitation Assessed Using Seattle Angina Questionnaire Physical Limitation Scale (SAQ-PL) at Week 4
The SAQ-PL measures how common daily activities representing low, medium, and high exertional requirements were limited by angina (9 items). It was scored by assigning each response an ordinal value, beginning with 1 for the response that implied the 'lowest level of functioning' to 5 for 'not at all limited', and summing across the 9 items. The score of 9 items was then transformed to 0-100 range by subtracting the lowest possible scale score, dividing by the range of the scale and multiplying by 100. The range of scores was 0 to 100, with higher scores indicates better functioning. A change of 10 points was considered to be clinically important.
Measured: Baseline, Week 4
Pharmacokinetic Parameter: SAR407899 Plasma Concentration
Measured: Day 1, 8, 15, 22, and Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2017
- Study start12 Oct 2017
- Primary completion23 Jul 2018
- Study completion23 Jul 2018
Why it stopped: (Recruitment was early terminated due to slow recruitment. Not linked to any safety concern.)
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.
- Other trials for Microvascular Coronary Artery DiseaseStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03236311
- Sponsor's protocol ID
- ACT14656
- Other IDs
- 2016-000629-38, U1111-1182-1709, 2016
- Status last verified
- Mar 2022
- First submitted
- 24 Jul 2017
- Last updated
- 24 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Parallel Arm Dose Titration Study to Assess the Effects of SAR407899 in Patients With Microvascular Angina (MVA) and/or Persistent Stable Angina Despite Angiographically Successful Percutaneous Coronary Intervention (PCI)
- ClinicalTrials.gov ID
- NCT03236311
- Acronym / sponsor ID
- ACT14656
- Conditions
- Microvascular Coronary Artery Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: (Recruitment was early terminated due to slow recruitment. Not linked to any safety concern.)
- Enrolment
- 10 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 12 Oct 2017 (actual)
- Primary completion
- 23 Jul 2018 (actual)
- Study completion
- 23 Jul 2018 (actual)
- First posted
- 1 Aug 2017 (actual)
- Results
- Posted 11 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To assess the effects of SAR407899 on coronary vasomotor function using the coronary flow reserve (CFR) in participants with microvascular angina (MVA) and/or persistent stable angina despite angiographically successful percutaneous coronary intervention (PCI).
Secondary Objectives:
- To assess the effects of SAR407899 on quality of life using Seattle Angina Questionnaire physical limitation scale (SAQ-PL) in participants with MVA and/or persistent stable angina despite angiographically successful PCI.
- To assess the safety of SAR407899 in participants with MVA and/or persistent stable angina despite angiographically successful PCI with a focus on identified risks such as hypotension and orthostatic hypotension.
- To assess SAR407899 plasma concentrations in MVA participants and/or persistent stable angina despite angiographically successful PCI.
Detailed description
The total duration of study per participant was:
- up to 9 weeks for participants with previous coronary artery angiography or coronary computed tomography angiography (CCTA) within 24 months prior to screening with up to 4 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration. or
- up to 11 weeks for participants with previous coronary artery angiography or CCTA between 24 months and 5 years prior to screening who need CCTA during screening period with up to 6 weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up after the last investigational medicinal product administration.
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Drug: Adenosine, Drug: Regadenoson, Drug: 13N-ammonia, Drug: 82RubidiumMatching placebo for 4 weeks. |
| SAR407899 | Experimental | Drug: SAR407899, Drug: Adenosine, Drug: Regadenoson, Drug: 13N-ammonia, Drug: 82RubidiumSAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female participants not at childbearing potential >=18 year-old or legal age of majority.
- Female participant if she has undergone sterilization at least 3 months earlier or was post-menopausal.
- Post-menopausal status was defined by having no menses for 12 months without an alternative medical cause.
- In females not treated with hormonal replacement therapy (HRT), menopausal status was confirmed by a high follicle stimulating hormone (FSH) level greater than 40 international units per litre (IU/L).
- In females on HRT and whose menopausal status was in doubt (i.e. in women aged less than 45 years), a highly effective contraception methods was required. Contraception was used during the whole study and for at least seven days corresponding to time needed to eliminate study treatment.
Key exclusion criteria (26 listed)
- Any use of nitrates (except short-acting nitrates) and/or dipyridamole and/or phosphodiesterase type 5 (PDE 5) inhibitors within one week prior to baseline PET scan or anticipated to be used during the study.
- Esophageal dysmotility or esophagitis.
- Participants with acute coronary syndrome (ACS) (myocardial infarction [MI] and/or unstable angina) in previous 3 months.
- Unsuccessful or incomplete coronary revascularization with residual obstructive stenosis or coronary artery disease (CAD) progression in native vessels as documented on invasive coronary angiography (>=50% stenosis) within 24 months of enrollment.
- Percutaneous coronary intervention performed at the time of an ACS (MI or unstable angina) in the previous 12 months.
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 |
|---|---|---|
| SAR407899Pharmaceutical form: Capsule Route of administration: Oral | Drug | SAR407899 |
| PlaceboPharmaceutical form: Capsule Route of administration: Oral | Drug | Placebo |
| AdenosinePharmaceutical form: Solution for injection Route of administration: Intravenous | Drug | Placebo, SAR407899 |
| RegadenosonPharmaceutical form: Solution for injection Route of administration: Intravenous | Drug | Placebo, SAR407899 |
| 13N-ammoniaPharmaceutical form: Solution for injection Route of administration: Intravenous | Drug | Placebo, SAR407899 |
| 82RubidiumPharmaceutical form: Solution for injection Route of administration: Intravenous | Drug | Placebo, SAR407899 |
Primary outcome
Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4
Time frame: Baseline, Week 4
Absolute change from baseline to Week 4 in uncorrected global CFR, as assessed by the central core laboratory. The global CFR is the ratio of absolute myocardial blood flow (MBF) at stress over that at rest. The MBF was assessed by 13N-ammonia or 82Rubidium positron emission tomography (PET) scan.
2 secondary outcomes
Change From Baseline in Angina-induced Physical Limitation Assessed Using Seattle Angina Questionnaire Physical Limitation Scale (SAQ-PL) at Week 4
Time frame: Baseline, Week 4
Pharmacokinetic Parameter: SAR407899 Plasma Concentration
Time frame: Day 1, 8, 15, 22, and Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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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
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SAR407899, Adenosine and Regadenoson in people with Microvascular Coronary Artery Disease, run by Sanofi at 10 sites in 5 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 11 inclusion and 26 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: stopped early, as of the sponsor's last update on 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Denmark, Netherlands, South Korea, Sweden. 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 11 Jul 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?
Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4 (time frame: Baseline, Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Mar 2022.