Trial Outcomes & Findings for A Dose Titration Study to Assess the Effects of SAR407899 in Patients With MVA and/or Persistent Stable Angina Despite Angiographically Successful PCI (NCT NCT03236311)

Last Updated: 2022-03-24

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2022-03-24

Participant Flow

The study was conducted in United States, South Korea, Sweden, Netherlands and Denmark from 12 Oct 2017 to 23 Jul 2018.

A total of 10 participants who met all of the inclusion criteria and none of the exclusion criteria were randomized and enrolled in the study.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo for 4 weeks.	SAR407899 SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
Overall Study STARTED	5	5
Overall Study COMPLETED	5	2
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo for 4 weeks.	SAR407899 SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
Overall Study Study terminated by sponsor	0	2
Overall Study Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=5 Participants Matching placebo for 4 weeks.	SAR407899 n=5 Participants SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).	Total n=10 Participants Total of all reporting groups
Age, Continuous	64.8 years STANDARD_DEVIATION 9.3 • n=5 Participants	57.2 years STANDARD_DEVIATION 8.5 • n=7 Participants	61.0 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Analysis was performed on modified intent-to-treat (mITT) population that included all randomized participants analyzed according to the treatment group allocated by randomization; who received at least 1 dose or part of a dose of the investigational medicinal product (IMP) and with an evaluable primary efficacy endpoint.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Matching placebo for 4 weeks.	SAR407899 n=2 Participants SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
Change From Baseline in Uncorrected Global Coronary Flow Reserve (CFR) at Week 4	0.5 ratio Standard Deviation 0.6	0.2 ratio Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: As the number of participants randomized fell well below target (10 vs. 78), hence no data was collected and no analysis was performed.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: As the number of participants randomized fell well below target (10 vs. 78), hence no data was collected and no analysis was performed.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

SAR407899

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=5 participants at risk Matching placebo for 4 weeks.	SAR407899 n=5 participants at risk SAR407899 with dose titration over 4 weeks administration (3 week titration phase + 1 week maintenance phase).
Cardiac disorders Angina Pectoris	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 2 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Ear and labyrinth disorders Vertigo	20.0% 1/5 • Number of events 2 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Gastrointestinal disorders Abdominal Pain	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
General disorders Non-Cardiac Chest Pain	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Infections and infestations Hordeolum	20.0% 1/5 • Number of events 2 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Infections and infestations Nasopharyngitis	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Injury, poisoning and procedural complications Contusion	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Injury, poisoning and procedural complications Sports Injury	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Nervous system disorders Dizziness	40.0% 2/5 • Number of events 2 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	40.0% 2/5 • Number of events 5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Nervous system disorders Dizziness Postural	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 4 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	40.0% 2/5 • Number of events 2 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Nervous system disorders Migraine	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 2 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.
Skin and subcutaneous tissue disorders Dermatitis Allergic	0.00% 0/5 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.	20.0% 1/5 • Number of events 1 • Adverse events (AE) were collected from signature of the informed consent form up to the end of follow up (up to Week 5 post-treatment follow-up visit) Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during 'the treatment emergent period' (the time from the first dose of study drug administration up to 7 days after the last dose of study drug administration). Analysis was performed on the safety population which included all randomized participants who received at least one dose or part of a dose of the IMP.