A Dose Titration Study to Assess the Effects of SAR407899 in Patients With MVA and/or Persistent Stable Angina Despite Angiographically Successful PCI

NCT03236311 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: ACT146562016-000629-38U1111-1182-1709
• Study Type: interventional
• Target: 10
• Locations: 5 countries
• Sites: 10

Brief 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). 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.

Conditions

Microvascular Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Baseline, Week 4

• Pharmacokinetic Parameter: SAR407899 Plasma Concentration

  Day 1, 8, 15, 22, and Day 29

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo for 4 weeks.

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).

Drug: SAR407899; Drug: Adenosine; Drug: Regadenoson; Drug: 13N-ammonia; Drug: 82Rubidium

Interventions

SAR407899 DRUG

Pharmaceutical form: Capsule Route of administration: Oral

SAR407899

Placebo DRUG

Pharmaceutical form: Capsule Route of administration: Oral

Placebo

Adenosine DRUG

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Placebo; SAR407899

Regadenoson DRUG

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Placebo; SAR407899

13N-ammonia DRUG

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Placebo; SAR407899

82Rubidium DRUG

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Placebo; SAR407899

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (10)

Investigational Site Number 8400003

Los Angeles, California, 90048, United States

Location

Investigational Site Number 8400001

Jacksonville, Florida, 32209, United States

Location

Investigational Site Number 8400013

Wellington, Florida, 33449, United States

Location

Investigational Site Number 8400008

Baltimore, Maryland, 21287, United States

Location

Investigational Site Number 8400006

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 8400010

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 2080001

København NV, 2400, Denmark

Location

Investigational Site Number 5280001

Nijmegen, 6525 GA, Netherlands

Location

Investigational Site Number 4100002

Seoul, 03722, South Korea

Location

Investigational Site Number 7520001

Lund, 221 85, Sweden

Location

MeSH Terms

Interventions

Adenosine; regadenoson

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

The study was prematurely terminated due to small number of participants entering randomization.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2017
• First Posted: August 1, 2017
• Study Start: October 12, 2017
• Primary Completion: July 23, 2018
• Study Completion: July 23, 2018
• Last Updated: March 24, 2022
• Results First Posted: July 11, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

KR (1); NL (1); DK (1); SE (1); US (6)