Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
This study is a Phase 2, randomized, double-blind, placebo controlled, pilot study designed to evaluate the efficacy and safety of PRM-151 administered through Week 24 to subjects with IPF.
Detailed description
PRM-151 is an anti-fibrotic immunomodulator being developed for treatment of fibrotic diseases.
Interventions
BIOLOGICALPRM-151
PRM 151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks
OTHERplacebo
Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Is aged 40-80 years. 2. Has IPF satisfying the American Thoracic Society/European Respiratory Society /Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) diagnostic criteria (Raghu, Collard et al. 2011). In the absence of a surgical lung biopsy, high-resolution computed tomography (HRCT) must be consistent with usual interstitial pneumonia (UIP) defined as meeting either criteria A, B, and C, or criteria A and C, or criteria B and C below: * Definite honeycomb lung destruction with basal and peripheral predominance. * Presence of reticular abnormality AND traction bronchiectasis consistent with fibrosis, with basal and peripheral predominance. * Atypical features are absent, specifically nodules and consolidation. Ground glass opacity, if present, is less extensive than reticular opacity pattern. 3. If on pirfenidone or nintedanib, subject must have been on a stable dose of pirfenidone or nintedanib for at least 3 months without increase in forced vital capacity (FVC)% predicted on two consecutive pulmonary function tests (PFTs), including screening PFTs. Subjects may not be on both pirfenidone and nintedanib. 4. If not currently receiving pirfenidone or nintedanib, subject must have been off pirfenidone or nintedanib for ≥ 4 weeks before baseline. 5. Has a FVC ≥ 50% and ≤ 90% of predicted. 6. Has a DLCO ≥ 25% and ≤ 90% of predicted. 7. Minimum distance on 6-Minute Walk Test (6MWT) of 150 meters. 8. Has a forced expiratory volume in 1 second (FEV1)/FVC ratio \> 0.70. 9. Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤ 55 years or 12 months if \> 55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception are defined in the protocol. 10. Has a life expectancy of at least 9 months 11. According to the investigator's best judgment, can comply with the requirements of the protocol. 12. Has provided written informed consent to participate in the study.
Exclusion criteria
1. Has emphysema ≥ 50% on HRCT or the extent of emphysema is greater than the extent of fibrosis according to reported results from the most recent HRCT. 2. Has a history of cigarette smoking within the previous 3 months. 3. Has received investigational therapy for IPF within 4 weeks before baseline. 4. Is receiving systemic corticosteroids equivalent to prednisone \> 10 mg/day or equivalent within 2 weeks of baseline. 5. Received azathioprine, cyclophosphamide, or cyclosporine A within 4 weeks of baseline. 6. Has a history of a malignancy within the previous 5 years, with the exception of basal cell skin neoplasms. In addition, a malignant diagnosis or condition first occurring prior to 5 years must be considered cured, inactive, and not under current treatment. 7. Has any concurrent condition other than IPF that, in the Investigator's opinion, is unstable and/or would impact the likelihood of survival for the study duration or the subject's ability to complete the study as designed, or may influence any of the safety or efficacy assessments included in the study. 8. Has baseline resting oxygen saturation of \< 89% on room air or supplemental oxygen. 9. Is unable to refrain from use of the following: * Short acting bronchodilators on the day of and within 12 hours of pulmonary function, DLCO, and 6 minute walk assessments. * Long acting bronchodilators on the day of and within 24 hours of these assessments. 10. Has a known post bronchodilator (short acting beta agonist \[SABA\] - albuterol or salbutamol) increase in FEV1 of \>10% and in FVC of \>7.5%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Vital Capacity (FVC) [% Predicted] | 0 to 28 weeks | Determine the effect size of PRM-151 relative to placebo in change from Baseline to Week 28 in mean FVC% predicted, pooling subjects on a stable dose of pirfenidone or nintedanib with subjects not on other treatment for IPF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Volume of Normal Lung on HRCT | 0 to 28 weeks | Mean change from baseline in volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software. |
| Change From Baseline in % of Normal Lung on HRCT (%) | 0 to 28 weeks | Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software. |
| Change From Baseline in 6-Minute Walk Distance (6MWD) | 0 to 28 weeks | — |
| Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT) | 0 to 28 weeks | Mean change from baseline in total lung volume on HRCT using quantitative imaging software. |
| Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT | 0 to 28 weeks | Mean change from baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software |
| Change From Baseline in % of Total Lung Volume of ILA on HRCT | 0 to 28 weeks | Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software |
| Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA | 0 to 28 weeks | Correlation between mean change from Baseline in FVC \[% predicted\] and mean change from Baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing by quantitative imaging software. |
| Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | 0 to 28 weeks | Pulmonary Function Tests for the Proportion (%) of subjects with a decline in FVC% predicted of ≥ 5% and ≥ 10% from Baseline to Week 28. |
| Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | 0 to 28 weeks | — |
| Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | 0 to 28 weeks | — |
| Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | 0 to 28 weeks | — |
| Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28. | 0 to 28 weeks | — |
| Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO). | 0 to 28 weeks | Pulmonary Function Tests to discern the mean change from Baseline to Week 28 in % predicted diffusion capacity of carbon monoxide (DLCO). |
| Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs) | 0 to 28 weeks | Tolerability/safety was assessed over the 28-week study period by the number of reported TEAEs |
| Percentage of Subjects Discontinuing Study Drug Due to AEs | 0 to 28 weeks | Tolerability/safety was assessed over the 28-week study period by the proportion of subjects who discontinued study drug due to AEs |
| Percentage of Subjects Reporting Serious Adverse Events (SAEs) | 0 to 28 weeks | Tolerability/safety was assessed over the 28-week study period by incidence of SAEs |
| Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability] | 0 to 28 weeks | Tolerability/safety was assessed over the 28-week study period by the number of reported serious respiratory decline AEs |
| Percentage of Subjects Reporting Respiratory Decline AEs | 0 to 28 weeks | Tolerability/safety was assessed over the 28-week study period by the number of reported respiratory decline AEs, defined as follows: * Unscheduled visits to a healthcare professional for respiratory status deterioration. * Urgent care visits for respiratory status deterioration. * Hospitalization due to a worsening or exacerbation of respiratory symptoms. |
| Percentage of Subjects With Infusion Related Reactions | 0 to 28 weeks | Infusion Related Reactions were defined as events of headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, shivers, hypertension, hypotension, lightheadedness, palpitations, urticaria and somnolence occurring between the start of a study treatment infusion and one hour after completion of the infusion. |
| All Cause Mortality | 0 to 28 weeks | Tolerability/safety was assessed over the 28-week study period by the incidence of all cause mortality |
| Mortality Due to Respiratory Deterioration | 0 to 28 weeks | Tolerability/safety was assessed over the 28-week study period by the incidence of mortality due to respiratory deterioration |
| Mortality Due to Disease Related Events | 0 to 28 weeks | Number of patients who died over the 28 week study period due to disease-related events (defined as cough, IPF exacerbation, IPF progression and respiratory decline AEs) |
| Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28. | 0 to 28 weeks | — |
Other
| Measure | Time frame |
|---|---|
| Change From Baseline in FVC Volume | 0 to 28 weeks |
Countries
Czechia, Germany, Italy, Netherlands, Spain, Switzerland, United States
Participant flow
Recruitment details
One hundred fifty-one (151) patients were screened for the study. Of these, one hundred seventeen (117) were found to be eligible and were randomized. One randomized patient dropped out of the study prior to receiving any study drug.
Participants by arm
| Arm | Count |
|---|---|
| PRM-151 10 mg/kg Dosing Every 4 Weeks
PRM-151: PRM 151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks | 77 |
| Placebo Dosing Every 4 weeks
placebo: Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks | 39 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open Label Extension | Study ongoing | 0 | 0 | 111 |
| Randomized Double Blind | Adverse Event | 3 | 1 | 0 |
| Randomized Double Blind | Disease progression | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | PRM-151 10 mg/kg | Placebo |
|---|---|---|---|
| 6MWD | 442.5 meters STANDARD_DEVIATION 101.7 | 434.8 meters STANDARD_DEVIATION 92.5 | 457.7 meters STANDARD_DEVIATION 117.7 |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 78 Participants | 53 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 24 Participants | 14 Participants |
| Comorbid Conditions Cardiac Disorders | 36 Participants | 29 Participants | 7 Participants |
| Comorbid Conditions Coronary Artery Disorders | 19 Participants | 15 Participants | 4 Participants |
| Comorbid Conditions Emphysema | 2 Participants | 2 Participants | 0 Participants |
| Comorbid Conditions GERD | 63 Participants | 47 Participants | 16 Participants |
| Comorbid Conditions Hypertension | 52 Participants | 38 Participants | 14 Participants |
| Comorbid Conditions Pulmonary Hypertension | 4 Participants | 1 Participants | 3 Participants |
| FEV1/FVC | 81.3 Percentage of FEV1/FVC STANDARD_DEVIATION 4.9 | 81.2 Percentage of FEV1/FVC STANDARD_DEVIATION 5.1 | 81.6 Percentage of FEV1/FVC STANDARD_DEVIATION 4.7 |
| FVC | 2743 mL STANDARD_DEVIATION 635 | 2733 mL STANDARD_DEVIATION 630 | 2763 mL STANDARD_DEVIATION 654 |
| FVC [% predicted] | 67.6 Percentage of predicted FVC STANDARD_DEVIATION 11 | 67.7 Percentage of predicted FVC STANDARD_DEVIATION 10.9 | 67.4 Percentage of predicted FVC STANDARD_DEVIATION 11.4 |
| Hemoglobin-corrected DLCO | 41.2 Percentage of predicted DLCO STANDARD_DEVIATION 9.7 | 40.1 Percentage of predicted DLCO STANDARD_DEVIATION 9.1 | 43.2 Percentage of predicted DLCO STANDARD_DEVIATION 10.5 |
| IPF Therapy Status at Baseline Concurrent IPF Therapy | 91 Participants | 61 Participants | 30 Participants |
| IPF Therapy Status at Baseline Concurrent nintedanib | 30 Participants | 22 Participants | 8 Participants |
| IPF Therapy Status at Baseline Concurrent pirfenidone | 61 Participants | 39 Participants | 22 Participants |
| IPF Therapy Status at Baseline IPF therapy naiive | 15 Participants | 8 Participants | 7 Participants |
| IPF Therapy Status at Baseline No concurrent IPF therapy | 25 Participants | 16 Participants | 9 Participants |
| Race/Ethnicity, Customized Ethnicity/Race Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity/Race Black/African | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity/Race Hispanic | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity/Race White | 113 Participants | 74 Participants | 39 Participants |
| Sex: Female, Male Female | 22 Participants | 12 Participants | 10 Participants |
| Sex: Female, Male Male | 94 Participants | 65 Participants | 29 Participants |
| SpO2 at rest | 95.6 Percentage of SpO2 STANDARD_DEVIATION 2 | 95.6 Percentage of SpO2 STANDARD_DEVIATION 2.1 | 95.5 Percentage of SpO2 STANDARD_DEVIATION 1.8 |
| Weight | 86.5 kg STANDARD_DEVIATION 14.5 | 86.1 kg STANDARD_DEVIATION 15.2 | 87.5 kg STANDARD_DEVIATION 13.4 |
| Years since IPF diagnosis, mean (SD) | 3.79 years STANDARD_DEVIATION 2.32 | 3.74 years STANDARD_DEVIATION 2.16 | 3.90 years STANDARD_DEVIATION 2.62 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 1 / 39 |
| other Total, other adverse events | 58 / 77 | 28 / 39 |
| serious Total, serious adverse events | 6 / 77 | 4 / 39 |
Outcome results
Primary
Change From Baseline in Forced Vital Capacity (FVC) [% Predicted]
Determine the effect size of PRM-151 relative to placebo in change from Baseline to Week 28 in mean FVC% predicted, pooling subjects on a stable dose of pirfenidone or nintedanib with subjects not on other treatment for IPF.
Time frame: 0 to 28 weeks
Population: All treated patients
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in Forced Vital Capacity (FVC) [% Predicted] | -2.5 Percentage of predicted FVC |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) [% Predicted] | -4.8 Percentage of predicted FVC |
Comparison: The sample size calculation was based on the following assumptions:~Normal distribution Homogeneity of variance the same in both arms, and for both types of patients Randomization ratio PRM-151:placebo = 2:1 Expected value for patients on pirfenidone or nintedanib = -1.5 Expected value for patients on no other treatment = -3 Expected value for patients on PRM-151 ≥ 0.75 Standard deviation = 5 75% of patients on a stable dose of pirfenidone or nintedanib α=0.10 two-sided Power = 80%p-value: 0.001490% CI: [1.1, 3.5]Mixed Models Analysis
Secondary
All Cause Mortality
Tolerability/safety was assessed over the 28-week study period by the incidence of all cause mortality
Time frame: 0 to 28 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | All Cause Mortality | 0 Participants |
| Placebo | All Cause Mortality | 1 Participants |
Secondary
Change From Baseline in 6-Minute Walk Distance (6MWD)
Time frame: 0 to 28 weeks
Population: All treated patients
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in 6-Minute Walk Distance (6MWD) | -0.5 meters |
| Placebo | Change From Baseline in 6-Minute Walk Distance (6MWD) | -31.8 meters |
p-value: 0.000290% CI: [17.4, 45.1]Mixed Models Analysis
Secondary
Change From Baseline in % of Normal Lung on HRCT (%)
Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software.
Time frame: 0 to 28 weeks
Population: All patients from the ATS population who had HRCT data at both the Baseline and Week 28 time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in % of Normal Lung on HRCT (%) | -2.6 percentage of total lung volume |
| Placebo | Change From Baseline in % of Normal Lung on HRCT (%) | -3.3 percentage of total lung volume |
| Placebo; No Background Therapy | Change From Baseline in % of Normal Lung on HRCT (%) | -1.4 percentage of total lung volume |
| Placebo; Pirfenidone or Nintedanib | Change From Baseline in % of Normal Lung on HRCT (%) | -2.1 percentage of total lung volume |
p-value: 0.5290% CI: [-4.4, 1.9]Mixed Models Analysis
Secondary
Change From Baseline in % of Total Lung Volume of ILA on HRCT
Mean change from baseline in % of total lung volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software
Time frame: 0 to 28 weeks
Population: All patients from the ATS population who had HRCT data at both the Baseline and Week 28 time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in % of Total Lung Volume of ILA on HRCT | 2.6 percentage of total lung volume |
| Placebo | Change From Baseline in % of Total Lung Volume of ILA on HRCT | 3.0 percentage of total lung volume |
| Placebo; No Background Therapy | Change From Baseline in % of Total Lung Volume of ILA on HRCT | 1.5 percentage of total lung volume |
| Placebo; Pirfenidone or Nintedanib | Change From Baseline in % of Total Lung Volume of ILA on HRCT | 1.9 percentage of total lung volume |
p-value: 0.583590% CI: [-2.2, 4.3]Mixed Models Analysis
Secondary
Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO).
Pulmonary Function Tests to discern the mean change from Baseline to Week 28 in % predicted diffusion capacity of carbon monoxide (DLCO).
Time frame: 0 to 28 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO). | -2.8 percentage of predicted DLCO |
| Placebo | Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO). | -3.0 percentage of predicted DLCO |
| Placebo; No Background Therapy | Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO). | -2.4 percentage of predicted DLCO |
| Placebo; Pirfenidone or Nintedanib | Change From Baseline in % Predicted Diffusion Capacity of Carbon Monoxide (DLCO). | -2.5 percentage of predicted DLCO |
p-value: 0.742490% CI: [-2.6, 1.7]Mixed Models Analysis
Secondary
Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT)
Mean change from baseline in total lung volume on HRCT using quantitative imaging software.
Time frame: 0 to 28 weeks
Population: All patients from the ATS population who had HRCT data at both the Baseline and Week 28 time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT) | -103.8 milliliters |
| Placebo | Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT) | -108.1 milliliters |
| Placebo; No Background Therapy | Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT) | -197.3 milliliters |
| Placebo; Pirfenidone or Nintedanib | Change From Baseline in Total Lung Volume on High-resolution Computed Tomography (HRCT) | -201.6 milliliters |
p-value: 0.203290% CI: [-27.7, 214.7]Mixed Models Analysis
Secondary
Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT
Mean change from baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing, using quantitative imaging software
Time frame: 0 to 28 weeks
Population: All patients from the ATS population who had HRCT data at both the Baseline and Week 28 time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT | 49.7 milliliters | Standard Error 49.65 |
| Placebo | Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT | 80.9 milliliters | Standard Error 29.21 |
| Placebo; No Background Therapy | Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT | 17.8 milliliters | Standard Error 55.26 |
| Placebo; Pirfenidone or Nintedanib | Change From Baseline in Volume of Interstitial Lung Abnormalities (ILA) on HRCT | 49.0 milliliters | Standard Error 39.64 |
p-value: 0.492790% CI: [-45, 108.8]Mixed Models Analysis
Secondary
Change From Baseline in Volume of Normal Lung on HRCT
Mean change from baseline in volume of parenchymal features on HRCT representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software.
Time frame: 0 to 28 weeks
Population: All patients from the ATS population who had HRCT data at both the Baseline and Week 28 time points.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in Volume of Normal Lung on HRCT | -165.2 milliliters |
| Placebo | Change From Baseline in Volume of Normal Lung on HRCT | -201.1 milliliters |
| Placebo; No Background Therapy | Change From Baseline in Volume of Normal Lung on HRCT | -208.8 milliliters |
| Placebo; Pirfenidone or Nintedanib | Change From Baseline in Volume of Normal Lung on HRCT | -244.7 milliliters |
p-value: 0.670790% CI: [-126.3, 213.5]Mixed Models Analysis
Secondary
Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA
Correlation between mean change from Baseline in FVC \[% predicted\] and mean change from Baseline in volume of parenchymal features on HRCT representative of ILA, including ground glass density, reticular changes, and honeycombing by quantitative imaging software.
Time frame: 0 to 28 weeks
Population: All patients from the ATS population who had FVC and HRCT data at both the Baseline and Week 28 time points.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRM-151 10 mg/kg | Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA | -0.5027 Correlation coefficient |
| Placebo | Correlation Between Mean Change From Baseline in FVC [% Predicted] and Mean Change From Baseline in ILA | -0.4570 Correlation coefficient |
p-value: 0.0001Pearson's correlation
Comparison: This study was not powered to test hypotheses beyond the primary endpoint.p-value: 0.0069Pearson's correlation
Secondary
Mortality Due to Disease Related Events
Number of patients who died over the 28 week study period due to disease-related events (defined as cough, IPF exacerbation, IPF progression and respiratory decline AEs)
Time frame: 0 to 28 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Mortality Due to Disease Related Events | 0 Participants |
| Placebo | Mortality Due to Disease Related Events | 0 Participants |
Secondary
Mortality Due to Respiratory Deterioration
Tolerability/safety was assessed over the 28-week study period by the incidence of mortality due to respiratory deterioration
Time frame: 0 to 28 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Mortality Due to Respiratory Deterioration | 0 Participants |
| Placebo | Mortality Due to Respiratory Deterioration | 1 Participants |
Secondary
Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28.
Time frame: 0 to 28 weeks
Population: All treated patients with data at baseline and Week 28
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRM-151 10 mg/kg | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 200 mL | 2 Participants |
| PRM-151 10 mg/kg | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 100 mL | 5 Participants |
| Placebo | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 100 mL | 32 Participants |
| Placebo | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 200 mL | 19 Participants |
| Placebo; No Background Therapy | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 200 mL | 1 Participants |
| Placebo; No Background Therapy | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 100 mL | 2 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 200 mL | 8 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With a Decline in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28. | Decrease in FVC ≥ 100 mL | 16 Participants |
p-value: 0.7773Mixed Models Analysis
p-value: 0.5976Mixed Models Analysis
Secondary
Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28.
Pulmonary Function Tests for the Proportion (%) of subjects with a decline in FVC% predicted of ≥ 5% and ≥ 10% from Baseline to Week 28.
Time frame: 0 to 28 weeks
Population: All treated patients with data at baseline and 28 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRM-151 10 mg/kg | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥ 5% | 2 Participants |
| PRM-151 10 mg/kg | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥10% | 1 Participants |
| Placebo | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥10% | 1 Participants |
| Placebo | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥ 5% | 18 Participants |
| Placebo; No Background Therapy | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥ 5% | 2 Participants |
| Placebo; No Background Therapy | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥10% | 0 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥ 5% | 11 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With a Decline in FVC [% Predicted] of ≥ 5% and ≥ 10% From Baseline to Week 28. | Decline in % Predicted FVC ≥10% | 3 Participants |
p-value: 0.4179Mixed Models Analysis
p-value: 0.2184Mixed Models Analysis
Secondary
Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28
Time frame: 0 to 28 weeks
Population: All treated patients with FVC data at Baseline and Week 28
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRM-151 10 mg/kg | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 100 mL | 1 Participants |
| PRM-151 10 mg/kg | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 200 mL | 0 Participants |
| Placebo | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 200 mL | 0 Participants |
| Placebo | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 100 mL | 6 Participants |
| Placebo; No Background Therapy | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 100 mL | 0 Participants |
| Placebo; No Background Therapy | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 200 mL | 0 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 100 mL | 0 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With an Increase in FVC of ≥ 100 mL and ≥ 200 mL From Baseline to Week 28 | Increase in FVC ≥ 200 mL | 0 Participants |
p-value: 0.0508Mixed Models Analysis
Secondary
Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28.
Time frame: 0 to 28 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRM-151 10 mg/kg | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥5% | 1 Participants |
| PRM-151 10 mg/kg | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥10% | 0 Participants |
| Placebo | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥10% | 0 Participants |
| Placebo | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥5% | 1 Participants |
| Placebo; No Background Therapy | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥5% | 0 Participants |
| Placebo; No Background Therapy | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥10% | 0 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥5% | 0 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With an Increase in FVC [% Predicted] of ≥ 5% and ≥10% From Baseline to Week 28. | Increase in % Predicted FVC ≥10% | 0 Participants |
p-value: 0.29Mixed Models Analysis
Secondary
Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28.
Time frame: 0 to 28 weeks
Population: All treated subjects with FVC data at Baseline and Week 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28. | 7 Participants |
| Placebo | Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28. | 16 Participants |
| Placebo; No Background Therapy | Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28. | 6 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With Stable Disease, Defined as a Change in FVC of < 100 mL From Baseline to Week 28. | 11 Participants |
p-value: 0.1846Mixed Models Analysis
Secondary
Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28.
Time frame: 0 to 28 weeks
Population: All treated subjects with data at baseline and week 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28. | 10 Participants |
| Placebo | Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28. | 35 Participants |
| Placebo; No Background Therapy | Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28. | 6 Participants |
| Placebo; Pirfenidone or Nintedanib | Number of Subjects With Stable Disease, Defined as a Change in FVC [% Predicted] of < 5% From Baseline to Week 28. | 16 Participants |
p-value: 0.6308Mixed Models Analysis
Secondary
Percentage of Subjects Discontinuing Study Drug Due to AEs
Tolerability/safety was assessed over the 28-week study period by the proportion of subjects who discontinued study drug due to AEs
Time frame: 0 to 28 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Percentage of Subjects Discontinuing Study Drug Due to AEs | 2 Participants |
| Placebo | Percentage of Subjects Discontinuing Study Drug Due to AEs | 1 Participants |
Secondary
Percentage of Subjects Reporting Respiratory Decline AEs
Tolerability/safety was assessed over the 28-week study period by the number of reported respiratory decline AEs, defined as follows: * Unscheduled visits to a healthcare professional for respiratory status deterioration. * Urgent care visits for respiratory status deterioration. * Hospitalization due to a worsening or exacerbation of respiratory symptoms.
Time frame: 0 to 28 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Percentage of Subjects Reporting Respiratory Decline AEs | 11 Participants |
| Placebo | Percentage of Subjects Reporting Respiratory Decline AEs | 4 Participants |
Secondary
Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability]
Tolerability/safety was assessed over the 28-week study period by the number of reported serious respiratory decline AEs
Time frame: 0 to 28 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability] | 4 Participants |
| Placebo | Percentage of Subjects Reporting Respiratory Decline SAEs [Safety and Tolerability] | 4 Participants |
Secondary
Percentage of Subjects Reporting Serious Adverse Events (SAEs)
Tolerability/safety was assessed over the 28-week study period by incidence of SAEs
Time frame: 0 to 28 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Percentage of Subjects Reporting Serious Adverse Events (SAEs) | 6 Participants |
| Placebo | Percentage of Subjects Reporting Serious Adverse Events (SAEs) | 4 Participants |
Secondary
Percentage of Subjects With Infusion Related Reactions
Infusion Related Reactions were defined as events of headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, shivers, hypertension, hypotension, lightheadedness, palpitations, urticaria and somnolence occurring between the start of a study treatment infusion and one hour after completion of the infusion.
Time frame: 0 to 28 weeks
Population: All treated patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PRM-151 10 mg/kg | Percentage of Subjects With Infusion Related Reactions | Any Infusion Related Reaction | 2 Participants |
| PRM-151 10 mg/kg | Percentage of Subjects With Infusion Related Reactions | Dizziness | 1 Participants |
| PRM-151 10 mg/kg | Percentage of Subjects With Infusion Related Reactions | Hypertensive crisis | 1 Participants |
| Placebo | Percentage of Subjects With Infusion Related Reactions | Any Infusion Related Reaction | 1 Participants |
| Placebo | Percentage of Subjects With Infusion Related Reactions | Dizziness | 0 Participants |
| Placebo | Percentage of Subjects With Infusion Related Reactions | Hypertensive crisis | 1 Participants |
Secondary
Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs)
Tolerability/safety was assessed over the 28-week study period by the number of reported TEAEs
Time frame: 0 to 28 weeks
Population: Safety population (All randomized patients who received at least one dose of study treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRM-151 10 mg/kg | Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs) | 71 Participants |
| Placebo | Percentage of Subjects With Treatment-emergent Adverse Events (TEAEs) | 36 Participants |
Other Pre-specified
Change From Baseline in FVC Volume
Time frame: 0 to 28 weeks
Population: All treated subjects
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PRM-151 10 mg/kg | Change From Baseline in FVC Volume | -127.7 milliliters |
| Placebo | Change From Baseline in FVC Volume | -242.3 milliliters |
p-value: 0.041690% CI: [22.2, 207.1]Mixed Models Analysis