Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
Primary Objective: To evaluate, in comparison with placebo, the efficacy of 2 dose levels/regimens of SAR156597 administered subcutaneously during 52 weeks on lung function of participants with Idiopathic Pulmonary Fibrosis (IPF). Secondary Objectives: To evaluate the efficacy of 2 dose levels/regimens of SAR156597 compared to placebo on IPF disease progression. To evaluate the safety of 2 dose levels/regimens of SAR156597 compared to placebo in participants with IPF.
Detailed description
The total study duration of study was expected up to 68 weeks (screening period of 4 weeks, treatment period of 52 weeks, and 12 weeks of follow up).
Interventions
DRUGSAR156597
Pharmaceutical form: solution for injection Route of administration: subcutaneous
DRUGplacebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Adult male or female participants. * Documented diagnosis of IPF according to the current 2011 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/ American Latin Thoracic Association (ATS/ERS/JRS/ALAT) guidelines. * Signed written informed consent.
Exclusion criteria
* Age less than or equal to 40 years. * IPF disease diagnosis greater than 5 years. * Forced vital capacity (FVC) less than (\<) 40 percent (%) of predicted value. * Carbon monoxide diffusing lung capacity (DLCO) corrected for hemoglobin \<30% of predicted value. * Severe chronic obstructive bronchitis as characterized by forced expiratory volume in 1 second /forced vital capacity (FEV1/FVC) \<0.70. * Need for 24 hours of oxygen therapy or oxygen saturation \<88% after 10 minutes breathing ambient air at rest. * Known diagnosis of significant respiratory disorders other than IPF. * Pulmonary artery hypertension requiring a specific treatment. * Currently listed and/or anticipated for lung transplantation within the next 6 months (on an active list). * History of vasculitis or connective tissue disorders. * Known human immunodeficiency virus or chronic viral hepatitis. * Participants with active tuberculosis or incompletely treated latent tuberculosis infection. * Use of any cytotoxic/immunosuppressive agent including but not limited to azathioprine, cyclophosphamide, methotrexate, and cyclosporine within 4 weeks prior to screening. * Use of any cytokine modulators (etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab, rituximab) within 12 weeks or 5 half-lives of screening (24 weeks for rituximab and 24 months for alefacept). * Use of any investigational drug within 1 month of screening, or 5 half-lives, if known ( whichever was longer), or within 12 weeks for stem cell therapy. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 | Baseline, Week 52 | FVC is a standard pulmonary function parameter measured by spirometry and used to quantify respiratory capacity (inspiration and expiration). It is a widely used objective measure of disease status in participants with Idiopathic Pulmonary Fibrosis (IPF). The primary variable was recorded as percent (%) of predicted value, which takes into account the height, gender, and age of the participant. The outcome measure measured the change in lung function from baseline at week 52. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression: Kaplan-Meier Estimates of Probability of Disease Progression at Week 52 | From randomization to disease progression (up to Week 52) | Disease progression was defined as the time from randomization to the first occurrence of any of the following events: decrease in absolute percent predicted FVC greater than or equal to (\>=) 10%, decrease in absolute percent predicted Carbon monoxide diffusing lung capacity \>=15%, lung transplant, or death. The median time to disease progression was not estimated because the number of occurrence of events was too low in the SAR156597 200 mg arms. |
| Time to Event: Kaplan-Meier Estimates of Probability of All Cause Mortality (Deaths) at Week 52 | From randomization up to Week 52 | All-cause mortality was considered for this outcome measure which was defined as the time from randomization to the date of death. The median time to event was not estimated because the number of all cause mortality was too low in the SAR156597 200 mg arms. |
Countries
Argentina, Australia, Canada, Chile, Colombia, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Mexico, Portugal, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 101 active centers in 19 countries. A total of 652 participants were screened between May 2015 and May 2016, of whom, 327 participants were randomized in 1:1:1 ratio to placebo: SAR156597 200 milligram (mg) once every 2 weeks (q2w): SAR156597 200 mg once every week (qw).
Pre-assignment details
Participants were stratified at the moment of randomization according to background therapy (participants with background anti-fibrotic therapy with either pirfenidone or nintedanib versus participants without background anti-fibrotic therapy).
Participants by arm
| Arm | Count |
|---|---|
| Placebo qw Participants received one injection of placebo (matched to SAR156597) subcutaneously qw for 52 weeks. | 110 |
| SAR156597 200mg q2w Participants received one injection of SAR156597 200 mg subcutaneously q2w alternating with placebo (matched to SAR156597) for 52 weeks. | 109 |
| SAR156597 200mg qw Participants received one injection of SAR156597 200 mg subcutaneously qw for 52 weeks. | 108 |
| Total | 327 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 8 | 16 |
| Overall Study | Other than specified above | 6 | 3 | 7 |
| Overall Study | Poor compliance to protocol | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo qw | SAR156597 200mg q2w | SAR156597 200mg qw | Total |
|---|---|---|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 8.6 | 67.4 years STANDARD_DEVIATION 7.2 | 68.0 years STANDARD_DEVIATION 7.6 | 68.1 years STANDARD_DEVIATION 7.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 7 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 105 Participants | 104 Participants | 99 Participants | 308 Participants |
| Sex: Female, Male Female | 22 Participants | 32 Participants | 27 Participants | 81 Participants |
| Sex: Female, Male Male | 88 Participants | 77 Participants | 81 Participants | 246 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 109 | 6 / 108 | 13 / 108 |
| other Total, other adverse events | 81 / 109 | 86 / 108 | 79 / 108 |
| serious Total, serious adverse events | 26 / 109 | 27 / 108 | 46 / 108 |
Outcome results
Primary
Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
FVC is a standard pulmonary function parameter measured by spirometry and used to quantify respiratory capacity (inspiration and expiration). It is a widely used objective measure of disease status in participants with Idiopathic Pulmonary Fibrosis (IPF). The primary variable was recorded as percent (%) of predicted value, which takes into account the height, gender, and age of the participant. The outcome measure measured the change in lung function from baseline at week 52.
Time frame: Baseline, Week 52
Population: Modified intent-to-treat (mITT) population: All participants who received at least 1 study injection, had valid baseline percent predicted FVC measurement, and had at least 1 post-baseline percent predicted FVC measurement. Here, 'Overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 | -5.81 percent predicted FVC | Standard Error 0.74 |
| SAR156597 200mg q2w | Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 | -5.24 percent predicted FVC | Standard Error 0.73 |
| SAR156597 200mg qw | Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 | -6.31 percent predicted FVC | Standard Error 0.75 |
Comparison: A hierarchical testing procedure was used to control type I error. Testing was done sequentially in order the outcome measures were reported. Analyzed using Mixed Model for Repeated Measurements (MMRM) with fixed categorical effects of treatment arm, stratification factor (with/without background therapy), time point, treatment-by-time point interaction, stratification factor-by-treatment-by-time point interaction, and continuous fixed covariate of percent predicted FVC baseline.p-value: =0.633995% CI: [-2.56, 1.56]Mixed Models Analysis
Comparison: A hierarchical testing procedure was used to control type I error. Testing was performed sequentially in the order outcome measures were reported (q2w dose group compared to placebo). Analysis was performed using MMRM with fixed categorical effects of treatment arm, stratification factor (with/without background therapy), time point, treatment-by-time point interaction, stratification factor-by-treatment-by-time point interaction, and continuous fixed covariate of percent predicted FVC baseline.p-value: =0.587495% CI: [-1.47, 2.6]Mixed Models Analysis
Secondary
Time to Disease Progression: Kaplan-Meier Estimates of Probability of Disease Progression at Week 52
Disease progression was defined as the time from randomization to the first occurrence of any of the following events: decrease in absolute percent predicted FVC greater than or equal to (\>=) 10%, decrease in absolute percent predicted Carbon monoxide diffusing lung capacity \>=15%, lung transplant, or death. The median time to disease progression was not estimated because the number of occurrence of events was too low in the SAR156597 200 mg arms.
Time frame: From randomization to disease progression (up to Week 52)
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo qw | Time to Disease Progression: Kaplan-Meier Estimates of Probability of Disease Progression at Week 52 | 0.512 probability of disease progression |
| SAR156597 200mg q2w | Time to Disease Progression: Kaplan-Meier Estimates of Probability of Disease Progression at Week 52 | 0.460 probability of disease progression |
| SAR156597 200mg qw | Time to Disease Progression: Kaplan-Meier Estimates of Probability of Disease Progression at Week 52 | 0.537 probability of disease progression |
Secondary
Time to Event: Kaplan-Meier Estimates of Probability of All Cause Mortality (Deaths) at Week 52
All-cause mortality was considered for this outcome measure which was defined as the time from randomization to the date of death. The median time to event was not estimated because the number of all cause mortality was too low in the SAR156597 200 mg arms.
Time frame: From randomization up to Week 52
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo qw | Time to Event: Kaplan-Meier Estimates of Probability of All Cause Mortality (Deaths) at Week 52 | 0.09 probability of deaths |
| SAR156597 200mg q2w | Time to Event: Kaplan-Meier Estimates of Probability of All Cause Mortality (Deaths) at Week 52 | 0.08 probability of deaths |
| SAR156597 200mg qw | Time to Event: Kaplan-Meier Estimates of Probability of All Cause Mortality (Deaths) at Week 52 | 0.13 probability of deaths |