Trial Outcomes & Findings for Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of SAR440340 (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT03546907)

Last Updated: 2022-11-22

Results Overview

Moderate exacerbations events were recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations events were defined as AECOPD requiring hospitalization, emergency medical care visit or resulting in death. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

343 participants

Primary outcome timeframe

From Baseline up to Week 52

Results posted on

2022-11-22

Participant Flow

The study was conducted at 83 centers in 10 countries, out of which 78 centers randomized at least 1 participant. A total of 653 participants were screened from 16-July-2018 to 01-April-2019, of which 310 participants were screen failures mainly due to selection criteria not met.

A total of 343 participants were randomized and treated in this study. Participants were randomized in 1:1 ratio to receive treatment SAR440340 and matching placebo for SAR440340.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to SAR440340 administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W). Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, End of Treatment \[EOT\] visit occurred 2 weeks after last administration of investigational medicinal product \[IMP\] i.e., at Week 52).	SAR440340 Participants received SAR440340 300 milligrams (mg) administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).
Overall Study STARTED	171	172
Overall Study COMPLETED	154	151
Overall Study NOT COMPLETED	17	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to SAR440340 administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W). Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, End of Treatment \[EOT\] visit occurred 2 weeks after last administration of investigational medicinal product \[IMP\] i.e., at Week 52).	SAR440340 Participants received SAR440340 300 milligrams (mg) administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).
Overall Study Lack of Efficacy	1	1
Overall Study Withdrawal by Subject	8	9
Overall Study Adverse events (AEs)	7	10
Overall Study Other-unspecified	1	1

Baseline Characteristics

Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of SAR440340 (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=171 Participants Participants received placebo matched to SAR440340 administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	SAR440340 n=172 Participants Participants received SAR440340 300 mg administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	Total n=343 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 6.5 • n=5 Participants	63.7 years STANDARD_DEVIATION 6.8 • n=7 Participants	63.9 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	73 Participants n=7 Participants	149 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	99 Participants n=7 Participants	194 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	0 Participants n=5 Participants	1 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	169 Participants n=5 Participants	170 Participants n=7 Participants	339 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age at diagnosis of chronic obstructive pulmonary disease (COPD)	55.5 years STANDARD_DEVIATION 8.0 • n=5 Participants	55.4 years STANDARD_DEVIATION 7.8 • n=7 Participants	55.4 years STANDARD_DEVIATION 7.9 • n=5 Participants
Mean number of moderate COPD exacerbations experienced within 1 year before screening visit	1.8 exacerbations STANDARD_DEVIATION 1.2 • n=5 Participants	1.8 exacerbations STANDARD_DEVIATION 1.1 • n=7 Participants	1.8 exacerbations STANDARD_DEVIATION 1.2 • n=5 Participants
Mean number of severe COPD exacerbations experienced within 1 year before screening visit	0.4 exacerbations STANDARD_DEVIATION 0.6 • n=5 Participants	0.3 exacerbations STANDARD_DEVIATION 0.6 • n=7 Participants	0.4 exacerbations STANDARD_DEVIATION 0.6 • n=5 Participants
Number of participants with smoking history Current	82 Participants n=5 Participants	74 Participants n=7 Participants	156 Participants n=5 Participants
Number of participants with smoking history Former	89 Participants n=5 Participants	98 Participants n=7 Participants	187 Participants n=5 Participants
Predicted baseline post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)	49.02 percent predicted FEVI STANDARD_DEVIATION 12.18 • n=5 Participants	49.62 percent predicted FEVI STANDARD_DEVIATION 12.34 • n=7 Participants	49.32 percent predicted FEVI STANDARD_DEVIATION 12.25 • n=5 Participants
Baseline COPD assessment test (CAT) score	21.66 score on a scale STANDARD_DEVIATION 5.23 • n=5 Participants	21.89 score on a scale STANDARD_DEVIATION 5.84 • n=7 Participants	21.78 score on a scale STANDARD_DEVIATION 5.54 • n=5 Participants
Standard of care background therapy LABA+LAMA	26 Participants n=5 Participants	23 Participants n=7 Participants	49 Participants n=5 Participants
Standard of care background therapy ICS+LABA	34 Participants n=5 Participants	33 Participants n=7 Participants	67 Participants n=5 Participants
Standard of care background therapy ICS+LAMA	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Standard of care background therapy ICS+LABA+LAMA	111 Participants n=5 Participants	115 Participants n=7 Participants	226 Participants n=5 Participants
Baseline blood eosinophil count	0.25 Giga cells per liter STANDARD_DEVIATION 0.19 • n=5 Participants	0.27 Giga cells per liter STANDARD_DEVIATION 0.24 • n=7 Participants	0.26 Giga cells per liter STANDARD_DEVIATION 0.22 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline up to Week 52

Population: Analysis was performed on modified intent-to-treat (mITT) population that included all randomized participants who had received at least 1 dose of IMP, analyzed according to the treatment group allocated by randomization.

Outcome measures

Outcome measures
Measure	Placebo n=171 Participants Participants received placebo matched to SAR440340 administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	SAR440340 n=172 Participants Participants received SAR440340 300 mg administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).
Annualized Rate of Moderate to Severe Acute Exacerbation Events in Chronic Obstructive Pulmonary Disease (AECOPD) Participants	1.610 exacerbation per participant-year Interval 1.318 to 1.968	1.301 exacerbation per participant-year Interval 1.052 to 1.61

SECONDARY outcome

Timeframe: From Baseline to Week 16 through Week 24

Population: Analysis was performed on mITT population.

FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. A mixed-effect model with repeated measures (MMRM) was first used to model the change from baseline at each post randomization timepoint up to Week 24, then the predicted values of Week 16 to Week 24 were averaged to provide an overall assessment of change from baseline in FEV1.

Outcome measures

Outcome measures
Measure	Placebo n=171 Participants Participants received placebo matched to SAR440340 administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	SAR440340 n=172 Participants Participants received SAR440340 300 mg administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).
Average Change in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) From Baseline to Week 16 Through Week 24	0.0 liters Standard Error 0.02	0.06 liters Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Analysis was performed on mITT population. Here, 'Overall number of participants analyzed ' signifies number of participants with available data for this outcome measure.

FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Post-bronchodilator FEV1 referred to the spirometry performed within 30 minutes after administration of bronchodilator (4 puffs of salbutamol/albuterol \[100 micrograms {mcg}\] or ipratropium bromide \[20 mcg\]).

Outcome measures

Outcome measures
Measure	Placebo n=163 Participants Participants received placebo matched to SAR440340 administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	SAR440340 n=165 Participants Participants received SAR440340 300 mg administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).
Change From Baseline in Post-bronchodilator Forced Expiratory Volume (FEV1) in 1 Second at Week 24	0.01 liters Standard Deviation 0.22	0.04 liters Standard Deviation 0.24

SECONDARY outcome

Timeframe: From Baseline up to 52 weeks

Population: Analysis was performed on mITT population.

The time to first moderate or severe exacerbation was defined as onset date of first moderate or severe AECOPD minus randomization date + 1. The median time to first severe exacerbation was derived from Kaplan-Meier estimates. Moderate exacerbations events were recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations events were defined as AECOPD requiring hospitalization, emergency medical care visit or resulting in death.

Outcome measures

Outcome measures
Measure	Placebo n=171 Participants Participants received placebo matched to SAR440340 administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	SAR440340 n=172 Participants Participants received SAR440340 300 mg administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).
Time to First Moderate or Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)	199.0 days Interval 139.0 to 266.0	277.0 days Interval 204.0 to Here, 'NA' signifies that the upper limit of 95% confidence interval was not computable because the curve that represents the upper confidence limits for the survivor function lies above 0.5.

Adverse Events

Placebo

Serious events: 36 serious events

Other events: 78 other events

Deaths: 2 deaths

SAR440340

Serious events: 29 serious events

Other events: 60 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=171 participants at risk Participants received placebo matched to SAR440340 administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	SAR440340 n=172 participants at risk Participants received SAR440340 300 mg administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).
Infections and infestations Bronchitis	8.2% 14/171 • Number of events 17 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.	9.3% 16/172 • Number of events 20 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.
Infections and infestations Nasopharyngitis	17.0% 29/171 • Number of events 43 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.	16.3% 28/172 • Number of events 40 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.
Infections and infestations Upper Respiratory Tract Infection	8.2% 14/171 • Number of events 17 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.	7.6% 13/172 • Number of events 17 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.
Nervous system disorders Headache	13.5% 23/171 • Number of events 35 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.	8.1% 14/172 • Number of events 24 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.
Vascular disorders Hypertension	6.4% 11/171 • Number of events 12 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.	1.7% 3/172 • Number of events 3 • From first administration of IMP up to 22 weeks after last dose of IMP (i.e., minimum up to 46 weeks and a maximum of up to 72 weeks) regardless of seriousness or relationship to IMP Analysis was performed on safety population that included all randomized participants who received at least 1 injection of IMP.

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.
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