Idiopathic Pulmonary Fibrosis
Conditions
Keywords
idiopathic pulmonary fibrosis, VAY736
Brief summary
The purpose of this study was to investigate the safety, tolerability and efficacy of VAY736 as potential therapy for the treatment of idiopathic pulmonary fibrosis (IPF).
Detailed description
This was an exploratory (non-confirmatory) randomized, patient-, investigator-, sponsor- blinded, placebo controlled study of VAY736 in IPF patients. This study investigated the safety and efficacy of 300 mg VAY736 administered subcutaneously (s.c.) every 4 weeks for 48 weeks. Participants were randomized in a 1:1 ratio on top of local standard of care (SOC), to receive VAY736 or placebo. Randomized subjects entered the treatment epoch (for up to 48 weeks), followed by two follow-up epochs: the PK/safety follow-up epoch and the PD/safety follow-up epoch. The PK/safety follow-up epoch lasted for 20 weeks. When the PK/safety follow-up epoch was completed, participants in the placebo arm were discharged from the study; but participants in the active arm (those who had received VAY736) continued into the PD/safety follow-up epoch. Participants in the PD/safety follow-up epoch were followed until B-cell recovery (in the peripheral blood), defined as: B cells \>=50/μL or B cells \>= 80% of baseline (whichever occurred first). If a participant had not recovered his/her B-cells after a period of 2 years from the last dose of VAY736, then this participant was discharged from the study.
Interventions
DRUGVAY736
300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks
DRUGPlacebo
Placebo administered subcutaneously every 4 weeks for 48 weeks
DRUGStandard of Care (SoC)
Background standard-of-care treatment for IPF: nintedanib, pirfenidone, or no background therapy
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of definite or probable IPF within 5 years of the screening visit * Forced Vital Capacity (FVC) 40-90% predicted (inclusive) * Diffusing Capacity of the Lungs (DLCO), corrected for hemoglobin, 25-79% predicted (inclusive) * Forced Expiratory Volume in first second (FEV1)/FVC \>70% * Unlikely to die from cause other than IPF within the next 3 years, in the opinion of the investigator * Unlikely to undergo lung transplantation during this trial
Exclusion criteria
* Emphysema \> fibrosis on screening high-resolution computed tomography (must be confirmed by central reader) * History of major organ, hematopoietic stem cell or bone marrow transplant * Clinically diagnosed acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) or other significant clinical worsening within 3 months of randomization * New York Heart Association (NYHA) class III/IV Congestive Heart Failure (CHF), Ejection Fraction (EF) \<25% * Current smoker * Prior use of any B-cell depleting therapy (e.g., rituximab, ofatumumab, or other anti-CD20 mAb, anti-CD40, anti-CD19,anti-CD22 mAb, anti-CD52 mAb, or anti-BAFF mAb)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC). | From baseline up to 48 weeks post first dose of study treatment | FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events | Up to 48 weeks post first dose of study treatment | IPF-related mortality events were defined as deaths due to IPF related cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided. |
| Percentage of Participants With Progression-free Survival (PFS) Events | Up to 48 weeks post first dose of study treatment | PFS events were divided into: 1) PFS1 events including progression (relative reduction in FVC ≥ 10%) or death due to all causes, and 2) PFS2 events including progression (relative reduction in FVC ≥ 10%) or death due to IPF-related causes. Kaplan-Meier estimates of the percentage of participants with the event of interest (PFS1 events or PFS2 events) along with 80% two-sided confidence intervals using Greenwood's formula are provided. |
| Percentage of Participants With Disease Progression Events | Up to 48 weeks post first dose of study treatment | The following disease progression events were considered: a) relative reduction in FVC ≥ 10%; b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15%; c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided. |
| Percentage of Participants With Composite Events | Up to 48 weeks post first dose of study treatment | Composite events were defined as: 1) death (all-cause mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 1); and 2) Death (IPF-related mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 2). Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided. |
| Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs | From baseline up to 48 weeks post first dose of study treatment | DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. DLCO was determined according to ATS guidelines. Change from baseline to end of treatment epoch (48 weeks of treatment) in diffusing capacity of the lung for carbon monoxide (DLCO) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date. |
| Percentage of Participants With All-cause Mortality Events | Up to 48 weeks post first dose of study treatment | All-cause mortality events were defined as deaths due to any cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided. |
| Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product | From baseline up to 48 weeks post first dose of study treatment | Distance saturation product is the product of distance walked and lowest oxygen saturation during the 6-min walk test. Change from baseline to end of treatment epoch (48 weeks of treatment) in distance saturation product was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date. |
| Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air) | From baseline up to 48 weeks post first dose of study treatment | Change from baseline to end of treatment epoch (48 weeks of treatment) in resting oxygen saturation (on room air) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date. |
| Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 1, 29, 85, 169, 253 and 337 | Number of participants with positive serum anti-VAY736 antibodies. A bridging ELISA method that is designed to detect the presence of anti-VAY736 antibodies in human serum was used. |
| Ctrough of VAY736 From the Serum Concentration-time Data | At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337 | The lowest serum concentration of VAY736 observed during a dosing interval at steady state (Ctrough) was determined |
| Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD) | From baseline up to 48 weeks post first dose of study treatment | A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The distance walked in six minutes (6MWD) was recorded. Change from baseline to end of treatment epoch (48 weeks of treatment) in 6MWD was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date. |
Countries
Canada, Germany, Ireland, Italy, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted across 16 centers in 6 countries.
Pre-assignment details
A total of 142 participants were screened of which 30 participants were randomized. 1 participant in the VAY736 arm did not receive treatment as the patient withdrew consent before first dosing. Treatment epoch (duration of up to 48 weeks) was followed by: i) PK/safety follow-up epoch with duration of 20 weeks, and ii) PD/safety follow-up (only for participants who had received VAY736) until participants met pre-specified criteria for B-Cell recover or up to 2 years from the last dose of VAY736.
Participants by arm
| Arm | Count |
|---|---|
| VAY736 Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy | 13 |
| Placebo Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy | 16 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| PD/Safety Follow-up Epoch | Lost to Follow-up | 1 | 0 |
| PD/Safety Follow-up Epoch | Subject/Guardian decision | 1 | 0 |
| Treatment Epoch | Adverse Event | 0 | 1 |
| Treatment Epoch | Discontinued early with reason other selected | 1 | 1 |
| Treatment Epoch | Study terminated by sponsor | 2 | 2 |
| Treatment Epoch | Subject/Guardian decision | 4 | 0 |
| Treatment Epoch | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | VAY736 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69.7 Years STANDARD_DEVIATION 9.3 | 68.3 Years STANDARD_DEVIATION 8.15 | 68.9 Years STANDARD_DEVIATION 8.55 |
| Race/Ethnicity, Customized White | 13 Participants | 16 Participants | 29 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 13 | 0 / 16 | 1 / 29 |
| other Total, other adverse events | 13 / 13 | 15 / 16 | 28 / 29 |
| serious Total, serious adverse events | 5 / 13 | 9 / 16 | 14 / 29 |
Outcome results
Primary
Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).
FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
Time frame: From baseline up to 48 weeks post first dose of study treatment
Population: Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAY736 | Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC). | 0.039 Liter (L) | Standard Error 0.1116 |
| Placebo | Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC). | -0.023 Liter (L) | Standard Error 0.0773 |
p-value: 0.324880% CI: [-0.115, 0.241]MMRM
Secondary
Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs
DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. DLCO was determined according to ATS guidelines. Change from baseline to end of treatment epoch (48 weeks of treatment) in diffusing capacity of the lung for carbon monoxide (DLCO) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
Time frame: From baseline up to 48 weeks post first dose of study treatment
Population: Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAY736 | Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs | -1.954 mililiter/minute/millimeter Mercury | Standard Error 1.0816 |
| Placebo | Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs | -1.033 mililiter/minute/millimeter Mercury | Standard Error 0.7244 |
p-value: 0.757680% CI: [-2.615, 0.774]MMRM
Secondary
Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD)
A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The distance walked in six minutes (6MWD) was recorded. Change from baseline to end of treatment epoch (48 weeks of treatment) in 6MWD was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
Time frame: From baseline up to 48 weeks post first dose of study treatment
Population: Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAY736 | Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD) | 19.743 Meter (m) | Standard Error 53.5268 |
| Placebo | Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD) | -12.479 Meter (m) | Standard Error 28.94 |
p-value: 0.301880% CI: [-47.572, 112.015]MMRM
Secondary
Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product
Distance saturation product is the product of distance walked and lowest oxygen saturation during the 6-min walk test. Change from baseline to end of treatment epoch (48 weeks of treatment) in distance saturation product was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
Time frame: From baseline up to 48 weeks post first dose of study treatment
Population: Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAY736 | Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product | 9.746 Meter% (m%) | Standard Error 52.2985 |
| Placebo | Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product | -19.420 Meter% (m%) | Standard Error 28.3755 |
p-value: 0.31480% CI: [-48.22, 106.553]MMRM
Secondary
Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air)
Change from baseline to end of treatment epoch (48 weeks of treatment) in resting oxygen saturation (on room air) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
Time frame: From baseline up to 48 weeks post first dose of study treatment
Population: Pharmacodynamic (PD) analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data. Only participants with a value at both Baseline and end of treatment (48 weeks post-first dose of treatment) were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAY736 | Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air) | -0.117 Percentage (%) | Standard Error 1.0179 |
| Placebo | Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air) | -1.887 Percentage (%) | Standard Error 0.9415 |
p-value: 0.126980% CI: [-0.219, 3.759]MMRM
Secondary
Ctrough of VAY736 From the Serum Concentration-time Data
The lowest serum concentration of VAY736 observed during a dosing interval at steady state (Ctrough) was determined
Time frame: At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337
Population: Overall number of participants analyzed represents the Pharmacokinetic (PK) analysis set including all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement who received at least one dose of VAY736 and with no protocol deviations that impact on PK data. The number of participants analyzed in each row represents the number of participants with a valid value in the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 1 | 0.00 nanogram (ng) / mililiter (mL) | Standard Deviation 0 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 29 | 676.79 nanogram (ng) / mililiter (mL) | Standard Deviation 499.931 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 57 | 779.89 nanogram (ng) / mililiter (mL) | Standard Deviation 645.363 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 85 | 786.63 nanogram (ng) / mililiter (mL) | Standard Deviation 501.225 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 113 | 771.88 nanogram (ng) / mililiter (mL) | Standard Deviation 623.268 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 141 | 1316.05 nanogram (ng) / mililiter (mL) | Standard Deviation 877.24 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 169 | 1019.00 nanogram (ng) / mililiter (mL) | Standard Deviation 587.097 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 197 | 985.50 nanogram (ng) / mililiter (mL) | Standard Deviation 495.652 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 225 | 1271.10 nanogram (ng) / mililiter (mL) | Standard Deviation 863.055 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 253 | 998.57 nanogram (ng) / mililiter (mL) | Standard Deviation 947.343 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 281 | 705.00 nanogram (ng) / mililiter (mL) | Standard Deviation 997.021 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 309 | 827.40 nanogram (ng) / mililiter (mL) | Standard Deviation 678.836 |
| VAY736 | Ctrough of VAY736 From the Serum Concentration-time Data | Day 337 | 688.50 nanogram (ng) / mililiter (mL) | Standard Deviation 1172.124 |
Secondary
Number of Participants With Positive Serum Anti-VAY736 Antibodies
Number of participants with positive serum anti-VAY736 antibodies. A bridging ELISA method that is designed to detect the presence of anti-VAY736 antibodies in human serum was used.
Time frame: Day 1, 29, 85, 169, 253 and 337
Population: Immunogenicity (IG) analysis set including all participants with at least one available valid (i.e. not flagged for exclusion) IG concentration measurement, who received any study drug and with no protocol deviations that impact on IG data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAY736 | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 169 | 0 Participants |
| VAY736 | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 85 | 1 Participants |
| VAY736 | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 253 | 2 Participants |
| VAY736 | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 29 | 1 Participants |
| VAY736 | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 337 | 0 Participants |
| VAY736 | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 1 | 1 Participants |
| Placebo | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 337 | 0 Participants |
| Placebo | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 1 | 3 Participants |
| Placebo | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 85 | 1 Participants |
| Placebo | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 169 | 2 Participants |
| Placebo | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 253 | 1 Participants |
| Placebo | Number of Participants With Positive Serum Anti-VAY736 Antibodies | Day 29 | 2 Participants |
Secondary
Percentage of Participants With All-cause Mortality Events
All-cause mortality events were defined as deaths due to any cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
Time frame: Up to 48 weeks post first dose of study treatment
Population: PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VAY736 | Percentage of Participants With All-cause Mortality Events | 8.3 Percentage of participants |
| Placebo | Percentage of Participants With All-cause Mortality Events | 0 Percentage of participants |
p-value: 0.868Log Rank
Secondary
Percentage of Participants With Composite Events
Composite events were defined as: 1) death (all-cause mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 1); and 2) Death (IPF-related mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 2). Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
Time frame: Up to 48 weeks post first dose of study treatment
Population: PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAY736 | Percentage of Participants With Composite Events | Composite Endpoint 1 | 81.0 Percentage of participants |
| VAY736 | Percentage of Participants With Composite Events | Composite Endpoint 2 | 79.2 Percentage of participants |
| Placebo | Percentage of Participants With Composite Events | Composite Endpoint 1 | 66.3 Percentage of participants |
| Placebo | Percentage of Participants With Composite Events | Composite Endpoint 2 | 66.3 Percentage of participants |
Comparison: Composite Endpoint 2p-value: 0.54980% CI: [0.6, 1.9]Log Rank
Comparison: Composite Endpoint 1p-value: 0.61180% CI: [0.6, 2]Log Rank
Secondary
Percentage of Participants With Disease Progression Events
The following disease progression events were considered: a) relative reduction in FVC ≥ 10%; b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15%; c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
Time frame: Up to 48 weeks post first dose of study treatment
Population: PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAY736 | Percentage of Participants With Disease Progression Events | FVC | 57.1 Percentage of participants |
| VAY736 | Percentage of Participants With Disease Progression Events | DLCO | 73.8 Percentage of participants |
| VAY736 | Percentage of Participants With Disease Progression Events | 6MWD | 38.3 Percentage of participants |
| Placebo | Percentage of Participants With Disease Progression Events | FVC | 31.9 Percentage of participants |
| Placebo | Percentage of Participants With Disease Progression Events | DLCO | 56.1 Percentage of participants |
| Placebo | Percentage of Participants With Disease Progression Events | 6MWD | 75.0 Percentage of participants |
Comparison: FVCp-value: 0.86380% CI: [0.9, 5.6]Log Rank
Comparison: DLCOp-value: 0.45780% CI: [0.4, 2]Log Rank
Comparison: 6MWDp-value: 0.01980% CI: [0.1, 0.6]Log Rank
Secondary
Percentage of Participants With Progression-free Survival (PFS) Events
PFS events were divided into: 1) PFS1 events including progression (relative reduction in FVC ≥ 10%) or death due to all causes, and 2) PFS2 events including progression (relative reduction in FVC ≥ 10%) or death due to IPF-related causes. Kaplan-Meier estimates of the percentage of participants with the event of interest (PFS1 events or PFS2 events) along with 80% two-sided confidence intervals using Greenwood's formula are provided.
Time frame: Up to 48 weeks post first dose of study treatment
Population: PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAY736 | Percentage of Participants With Progression-free Survival (PFS) Events | PFS1 | 61.0 Percentage of participants |
| VAY736 | Percentage of Participants With Progression-free Survival (PFS) Events | PFS2 | 57.1 Percentage of participants |
| Placebo | Percentage of Participants With Progression-free Survival (PFS) Events | PFS1 | 31.9 Percentage of participants |
| Placebo | Percentage of Participants With Progression-free Survival (PFS) Events | PFS2 | 31.9 Percentage of participants |
Comparison: PFS1p-value: 0.92180% CI: [1.1, 6.3]Log Rank
Comparison: PFS2p-value: 0.86380% CI: [0.9, 5.6]Log Rank
Secondary
Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events
IPF-related mortality events were defined as deaths due to IPF related cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood's formula are provided.
Time frame: Up to 48 weeks post first dose of study treatment
Population: PD analysis set including participants with available PD data and no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VAY736 | Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events | 0 Percentage of participants |
| Placebo | Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events | 0 Percentage of participants |