Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Idiopathic Pulmonary Fibrosis, IPF, Idiopathic Interstitial Pneumonia, Interstitial Lung Disease, Lung Fibrosis
Brief summary
To evaluate the safety and tolerability of pamrevlumab in participants with IPF, and the efficacy of pamrevlumab in slowing the loss of forced vital capacity (FVC) and the progression of IPF in these participants.
Detailed description
The study has been amended in February 2016 to further allow for the enrollment of a subgroup of participants (N=60) who will be allowed to receive treatment with approved IPF therapy with pirfenidone or with nintedanib as concomitant therapy. These additional participants will be stratified by background therapy, randomized to pamrevlumab or placebo, and followed up for 24 weeks. The main objective of the study remains safety. Pharmacokinetic (PK) samples to assess drug concentrations will also be collected. This sub-study portion only applies to a select United States centers. Enrollment for the main study was completed on 29 June 2016. Enrollment for the sub-study was completed on 16 December 2016.
Interventions
DRUGPamrevlumab
Solution for infusion
DRUGPlacebo
Solution for infusion
DRUGSub-Study: Pirfenidone
Pirfenidone concomitant therapy will not be provided by the Sponsor.
DRUGSub-Study: Nintedanib
Nintedanib concomitant therapy will not be provided by the Sponsor.
Sponsors
FibroGen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, Investigators, and study staff were blinded to treatment assignments and did not have access to the randomization codes. The high-resolution computed tomography (HRCT) readers were blinded to treatment assignments.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 40 to 80 years, inclusive. 2. Diagnosis of IPF as defined by current international guidelines. Each participant must have 1 of the following: (1) Usual Interstitial Pneumonia (UIP) Pattern on an available high-resolution computed tomography (HRCT) scan; or (2) Possible UIP Pattern on an available HRCT scan and surgical lung biopsy within 4 years of Screening showing UIP Pattern. 3. History of IPF of ≤5 years duration with onset defined as the date of the first diagnosis of IPF by HRCT or surgical lung biopsy. 4. Interstitial pulmonary fibrosis defined by HRCT scan at Screening, with evidence of ≥10% to \<50% parenchymal fibrosis (reticulation) and \<25% honeycombing, within the whole lung, as determined by the HRCT central reader. 5. FVC percent of predicted value ≥55% at Screening. 6. Female participants of childbearing potential (including those \<1 year postmenopausal) must be willing to use a medically acceptable method of contraception, for example, an oral contraceptive, depot progesterone, or intrauterine device. Male participants with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (for example, condom) if not surgically sterile (for example, vasectomy). 7. For sub-study only: Receiving treatment for IPF with a stable dose of pirfenidone or with a stable dose of nintedanib for at least 3 months before Screening initiation and willing to continue treatment with pirfenidone or with nintedanib according to the corresponding approved label and the prescribing physician, including all listed safety requirements (for example, liver function tests, avoidance of sunlight and sunlamp exposure and wearing of sunscreen and protective clothing daily for pirfenidone, and smoking cessation).
Exclusion criteria
1. Women who are pregnant or nursing. 2. Infiltrative lung disease other than IPF, including any of the other types of idiopathic interstitial pneumonias (Travis, 2013); lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs; other types of occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including vasculitis and connective tissue diseases. 3. HRCT scan findings at Screening are inconsistent with UIP Pattern, as determined by the HRCT central reader. 4. Pathology diagnosis on surgical lung biopsy is anything other than UIP Pattern, as determined by the local pathologist. 5. The Investigator judges that there has been sustained improvement in the severity of IPF during the 12 months prior to Screening, based on changes in FVC, diffusing capacity of the lung for carbon monoxide (DLCO), and/or HRCT scans of the chest. 6. Clinically important abnormal laboratory tests. 7. Upper or lower respiratory tract infection of any type within 4 weeks of the first Screening visit. 8. Acute exacerbation of IPF within 3 months of the first Screening visit. 9. Use of medications to treat IPF within 5 half-lives of Day 1 dosing. If monoclonal antibodies were used, the last dose of the antibody must be at least 4 weeks before Day 1 dosing. This applies to participants enrolled in Main Study only. 10. Use of any investigational drugs, including any investigational drugs for IPF, within 4 weeks prior to Day 1 dosing. 11. History of cancer diagnosis of any type in the 3 years preceding Screening, excluding non-melanomatous skin cancer, localized bladder cancer, or in situ cancers. 12. Diffusing capacity (DLCO) less than 30% of predicted value. 13. History of allergic or anaphylactic reaction to human, humanized, chimeric, or murine monoclonal antibodies. 14. Previous treatment with FG-3019. 15. Body weight greater than 130 kilograms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48 | Baseline (Screening and Day 1), Week 48 | FVC in liters was measured during the spirometry assessments at screening and during the randomized treatment period at Day 1 and every 12 weeks. The FVC (% predicted) was calculated for the corresponding gender-race-age group. The least squares (LS) mean change from Baseline to Week 48 (end of the randomized treatment period) in FVC (% predicted) is presented. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Other statistical analysis data is reported in the statistical analysis section. Observed data from all visits were included in the model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With IPF Progression Events up to Week 48 | Baseline (Screening and Day 1) up to Week 48 | IPF progression events included death from any cause or absolute decline in FVC (% predicted) value of ≥10%, confirmed by repeat spirometry. Classification of FVC (% predicted) declined ≥10% was based on observed and imputed data. Missing data in FVC (% predicted) were imputed using the predicted values from the random coefficient module with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope as random effect. |
| Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Baseline (Day 1), Week 24 and Week 48 | HRQoL was assessed by the SGRQ to measure health impairment, and includes 17 questions in 3 domains: Symptoms, Activity and Impacts. The domain and total scores range from 0 to 100, with 0 indicating the best and 100 indicating the worst possible health status. Missing data at post-baseline visits were imputed as the predicted values from the random coefficient model which included treatment, visit, visit-by-treatment interaction, and Baseline SGRQ score as fixed effects and linear slope of visit as random effect. |
| Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 | Baseline (Screening), Week 24 and Week 48 | The extent of pulmonary fibrosis was measured by HRCT scans of the chest at screening and at Weeks 24 and 48, to determine the HRCT QLF score. Each lung was divided into 5 lobes (right upper, right middle, right lower, left upper, left lower). For the quantitative HRCT analyses, a computer read the images and quantified the percent (%) and volume (mL) of fibrosis for the whole lung by averaging the scores from each of 5 lung lobes. Baseline was defined as the Screening evaluation. Missing data were imputed using the multiple imputation (MI) method to handle missing values. |
| Number of Participants With a Respiratory-Related Death | Week 55 | Investigators determined whether a death was respiratory-related. |
| Number of Participants With No Decline in FVC (% Predicted) at Week 48 | Baseline (Day 1) to Week 48. | FVC in liters was measured during the spirometry assessments. The FVC (% predicted) was calculated for the corresponding gender-race-age group. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Classification of 'No decline' is based on observed and imputed data. Missing data in FVC (% predicted) are imputed using the predicted values from the random coefficient model with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope of visit as random effect. |
| Number of Participants With a Respiratory-Related Hospitalization | Week 55 | Respiratory-related hospitalizations were reported by participants and recorded by the Investigators. |
Countries
Australia, Bulgaria, Canada, India, New Zealand, South Africa, United States
Participant flow
Recruitment details
Adult participants with a history of idiopathic pulmonary fibrosis (IPF) ≤5 years duration and a forced vital capacity (FVC) predicted value ≥55% at screening were randomized to receive pamrevlumab or placebo.
Pre-assignment details
This Phase 2 study was conducted at 44 study centers in 7 countries from July 2013 to November 2017.
Participants by arm
| Arm | Count |
|---|---|
| Pamrevlumab Participants received pamrevlumab 30 mg/kg by IV infusion every 3 weeks for a total of 16 infusions over 45 weeks. | 50 |
| Placebo Participants received placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 16 infusions over 45 weeks. | 53 |
| Sub-Study: Pamrevlumab+Pirfenidone Participants received pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with pamrevlumab in all active comparator participants was administered at a dose of 15 mg/kg for the first 2 dose administrations. If these were well tolerated, all following study drug administrations were at 30 mg/kg.
Pirfenidone was dosed according to the instructions in the label and the prescribing physician. | 24 |
| Sub-Study:Placebo+Pirfenidone Participants received placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with placebo in all active comparator participants were administered at a dose of 15 mg/kg for the first 2 dose administrations. If these were well tolerated, all following study drug administrations were at 30 mg/kg.
Pirfenidone was dosed according to the instructions in the label and the prescribing physician. | 12 |
| Sub-Study:Pamrevlumab+Nintedanib Participants received pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with pamrevlumab in all active comparator participants was administered at a dose of 15 mg/kg for the first 2 dose administrations. If these were well tolerated, all following study drug administrations were at 30 mg/kg.
Nintedanib was dosed according to the instructions in the label and the prescribing physician. | 15 |
| Sub-Study: Placebo+Nintedanib Participants received placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with placebo in all active comparator participants were administered at a dose of 15 mg/kg for the first 2 dose administrations. If these were well tolerated, all following study drug administrations were at 30 mg/kg.
Nintedanib was dosed according to the instructions in the label and the prescribing physician. | 6 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 2 | 3 | 1 | 0 | 0 | 0 |
| Overall Study | Other (Unspecified reason) | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 6 | 6 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 3 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Sub-Study: Placebo+Nintedanib | Total | Pamrevlumab | Placebo | Sub-Study: Pamrevlumab+Pirfenidone | Sub-Study:Placebo+Pirfenidone | Sub-Study:Pamrevlumab+Nintedanib |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 4.62 | 68.5 years STANDARD_DEVIATION 6.82 | 68.3 years STANDARD_DEVIATION 7.05 | 68.4 years STANDARD_DEVIATION 7.2 | 68.6 years STANDARD_DEVIATION 6.27 | 68.4 years STANDARD_DEVIATION 5.5 | 71.1 years STANDARD_DEVIATION 7.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 101 Participants | 49 Participants | 52 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 59 Participants | 1 Participants | 1 Participants | 24 Participants | 12 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Asian | 0 Participants | 8 Participants | 5 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Other | 0 Participants | 9 Participants | 4 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race White | 6 Participants | 142 Participants | 41 Participants | 44 Participants | 24 Participants | 12 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 43 Participants | 17 Participants | 10 Participants | 7 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 117 Participants | 33 Participants | 43 Participants | 17 Participants | 8 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 50 | 3 / 53 | 1 / 24 | 0 / 12 | 0 / 15 | 0 / 6 |
| other Total, other adverse events | 42 / 50 | 41 / 53 | 19 / 24 | 12 / 12 | 14 / 15 | 6 / 6 |
| serious Total, serious adverse events | 12 / 50 | 8 / 53 | 2 / 24 | 1 / 12 | 0 / 15 | 1 / 6 |
Outcome results
Primary
Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48
FVC in liters was measured during the spirometry assessments at screening and during the randomized treatment period at Day 1 and every 12 weeks. The FVC (% predicted) was calculated for the corresponding gender-race-age group. The least squares (LS) mean change from Baseline to Week 48 (end of the randomized treatment period) in FVC (% predicted) is presented. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Other statistical analysis data is reported in the statistical analysis section. Observed data from all visits were included in the model.
Time frame: Baseline (Screening and Day 1), Week 48
Population: Randomized participants who met all protocol eligibility criteria (ITT population). Data for the participants who were included in the pamrevlumab and placebo arms in the Main Study were collected for this Outcome Measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pamrevlumab | Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48 | Baseline | 74.51 % predicted FVC | Standard Error 1.682 |
| Pamrevlumab | Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48 | Change from Baseline at Week 48 | -2.71 % predicted FVC | Standard Error 0.624 |
| Placebo | Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48 | Baseline | 72.82 % predicted FVC | Standard Error 1.512 |
| Placebo | Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48 | Change from Baseline at Week 48 | -7.20 % predicted FVC | Standard Error 1.664 |
Comparison: The absolute LS mean treatment difference (pamrevlumab - placebo) for change from Baseline to Week 48 in FVC (% predicted) is presented.p-value: =0.033195% CI: [0.35, 8.3]Random coefficient regression
Secondary
Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48
HRQoL was assessed by the SGRQ to measure health impairment, and includes 17 questions in 3 domains: Symptoms, Activity and Impacts. The domain and total scores range from 0 to 100, with 0 indicating the best and 100 indicating the worst possible health status. Missing data at post-baseline visits were imputed as the predicted values from the random coefficient model which included treatment, visit, visit-by-treatment interaction, and Baseline SGRQ score as fixed effects and linear slope of visit as random effect.
Time frame: Baseline (Day 1), Week 24 and Week 48
Population: Randomized participants who met all protocol eligibility criteria (ITT population) and who also had a baseline and at least 1 follow-up value. Data for the participants who were included in the pamrevlumab and placebo arms in the Main Study were collected for this Outcome Measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Symptoms Score at Baseline | 48.32 score on a scale | Standard Error 3.194 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Symptoms Score Change from Baseline at Week 24 | -0.36 score on a scale | Standard Error 2.045 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Symptoms Score Change from Baseline at Week 48 | -3.06 score on a scale | Standard Error 2.336 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Activity Score at Baseline | 55.69 score on a scale | Standard Error 4.038 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Activity Score Change from Baseline at Week 24 | -0.05 score on a scale | Standard Error 1.889 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Activity Score Change from Baseline at Week 48 | -4.06 score on a scale | Standard Error 2.432 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Impacts Score at Baseline | 31.38 score on a scale | Standard Error 3.361 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Impacts Score Change from Baseline at Week 24 | -1.08 score on a scale | Standard Error 1.518 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Impacts Score Change from Baseline at Week 48 | -1.77 score on a scale | Standard Error 2.306 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Total Score at Baseline | 41.75 score on a scale | Standard Error 3.229 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Total Score Change from Baseline at Week 24 | -0.63 score on a scale | Standard Error 1.22 |
| Pamrevlumab | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Total Score Change from Baseline at Week 48 | -2.75 score on a scale | Standard Error 1.729 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Total Score Change from Baseline at Week 24 | -0.73 score on a scale | Standard Error 1.899 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Symptoms Score at Baseline | 50.43 score on a scale | Standard Error 2.579 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Impacts Score at Baseline | 31.28 score on a scale | Standard Error 2.766 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Symptoms Score Change from Baseline at Week 24 | -1.74 score on a scale | Standard Error 2.205 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Total Score at Baseline | 43.55 score on a scale | Standard Error 2.39 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Symptoms Score Change from Baseline at Week 48 | 1.56 score on a scale | Standard Error 2.675 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Impacts Score Change from Baseline at Week 24 | -0.50 score on a scale | Standard Error 2.238 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Activity Score at Baseline | 60.46 score on a scale | Standard Error 2.803 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Total Score Change from Baseline at Week 48 | 2.46 score on a scale | Standard Error 2.719 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Activity Score Change from Baseline at Week 24 | 0.26 score on a scale | Standard Error 1.948 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Impacts Score Change from Baseline at Week 48 | 3.04 score on a scale | Standard Error 3.106 |
| Placebo | Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48 | Activity Score Change from Baseline at Week 48 | 1.35 score on a scale | Standard Error 2.599 |
Secondary
Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48
The extent of pulmonary fibrosis was measured by HRCT scans of the chest at screening and at Weeks 24 and 48, to determine the HRCT QLF score. Each lung was divided into 5 lobes (right upper, right middle, right lower, left upper, left lower). For the quantitative HRCT analyses, a computer read the images and quantified the percent (%) and volume (mL) of fibrosis for the whole lung by averaging the scores from each of 5 lung lobes. Baseline was defined as the Screening evaluation. Missing data were imputed using the multiple imputation (MI) method to handle missing values.
Time frame: Baseline (Screening), Week 24 and Week 48
Population: Randomized participants who met all protocol eligibility criteria (ITT population) and who also had a baseline fibrosis evaluation. Data for the participants who were included in the pamrevlumab and placebo arms in the Main Study were collected for this Outcome Measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pamrevlumab | Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 | Baseline | 13.9 Percent of fibrosis | Standard Error 1.44 |
| Pamrevlumab | Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 | Change from Baseline at Week 24 | 0.8 Percent of fibrosis | Standard Error 0.34 |
| Pamrevlumab | Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 | Change from Baseline at Week 48 | 2.7 Percent of fibrosis | Standard Error 0.47 |
| Placebo | Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 | Baseline | 14.7 Percent of fibrosis | Standard Error 1.09 |
| Placebo | Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 | Change from Baseline at Week 24 | 2.6 Percent of fibrosis | Standard Error 0.55 |
| Placebo | Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 | Change from Baseline at Week 48 | 6.0 Percent of fibrosis | Standard Error 1.15 |
Comparison: The absolute LS mean treatment difference (pamrevlumab - placebo) for change from Baseline to Week 24 in QLF score is presented.p-value: =0.023695% CI: [-3.3, -0.2]ANCOVA with MI
Comparison: The absolute LS mean treatment difference (pamrevlumab - placebo) for change from Baseline to Week 48 in QLF score is presented.p-value: =0.072995% CI: [-6.6, 0.3]ANCOVA with MI
Secondary
Number of Participants With a Respiratory-Related Death
Investigators determined whether a death was respiratory-related.
Time frame: Week 55
Population: Randomized participants who received any amount of study medication (Safety Population). Data for the participants who were included in the pamrevlumab and placebo arms in the Main Study were collected for this Outcome Measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants With a Respiratory-Related Death | 2 Participants |
| Placebo | Number of Participants With a Respiratory-Related Death | 3 Participants |
Secondary
Number of Participants With a Respiratory-Related Hospitalization
Respiratory-related hospitalizations were reported by participants and recorded by the Investigators.
Time frame: Week 55
Population: Randomized participants who received any amount of study medication (Safety Population). Data for the participants who were included in the pamrevlumab and placebo arms in the Main Study were collected for this Outcome Measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants With a Respiratory-Related Hospitalization | 5 Participants |
| Placebo | Number of Participants With a Respiratory-Related Hospitalization | 7 Participants |
Secondary
Number of Participants With IPF Progression Events up to Week 48
IPF progression events included death from any cause or absolute decline in FVC (% predicted) value of ≥10%, confirmed by repeat spirometry. Classification of FVC (% predicted) declined ≥10% was based on observed and imputed data. Missing data in FVC (% predicted) were imputed using the predicted values from the random coefficient module with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope as random effect.
Time frame: Baseline (Screening and Day 1) up to Week 48
Population: Randomized participants who met all protocol eligibility criteria (ITT population). Data for the participants who were included in the pamrevlumab and placebo arms in the Main Study were collected for this Outcome Measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants With IPF Progression Events up to Week 48 | 5 Participants |
| Placebo | Number of Participants With IPF Progression Events up to Week 48 | 16 Participants |
Comparison: The absolute treatment difference (pamrevlumab - placebo) for percentage of participants with IPF progression at Week 48 is presented.p-value: =0.013395% CI: [-36.6, -6.2]Regression, Logistic
Secondary
Number of Participants With No Decline in FVC (% Predicted) at Week 48
FVC in liters was measured during the spirometry assessments. The FVC (% predicted) was calculated for the corresponding gender-race-age group. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Classification of 'No decline' is based on observed and imputed data. Missing data in FVC (% predicted) are imputed using the predicted values from the random coefficient model with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope of visit as random effect.
Time frame: Baseline (Day 1) to Week 48.
Population: Randomized participants who met all protocol eligibility criteria (ITT population). Data for the participants who were included in the pamrevlumab and placebo arms in the Main Study were collected for this Outcome Measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pamrevlumab | Number of Participants With No Decline in FVC (% Predicted) at Week 48 | 11 Participants |
| Placebo | Number of Participants With No Decline in FVC (% Predicted) at Week 48 | 13 Participants |