Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
A phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety, tolerability, biological activity, and pharmacokinetics (PK) of ND-L02-s0201 for Injection in subjects with IPF.
Detailed description
All subjects were treated with ND-L02-s0201 or placebo for 24 weeks (a total of 12 doses). Subject's participation in the study was approximately 40 weeks including a Screening and Baseline period of up to 6 weeks, a treatment period of 24 weeks (including the 2 weeks after the last study treatment), and a follow-up period of 10 weeks after End-of-Treatment (EOT).
Interventions
DRUGND-L02-s0201 (Low Dose)
Intravenous administration every 2 weeks
DRUGND-L02-s0201 (High Dose)
Intravenous administration every 2 weeks
OTHEROther: Placebo
Saline
Sponsors
Nitto Denko Corporation
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
* Forced vital capacity (FVC) ≥ 45% of predicted. * Diffusion capacity of the lung for carbon monoxide (DLco) corrected for hemoglobin ≥ 30% of predicted value * Ratio of forced expiratory volume in 1 second (FEV1) to FVC ≥ 0.70.
Exclusion criteria
* Best, acceptable FVC from separate screening spirometry that differ by ≥ 200 mL. * Respiratory exacerbation(s) or hospitalization for IPF exacerbation within 3 months before screening. * Anticipated to receive a lung transplant during the subject's participation in the study. * Active smoker or smoking cessation within 12 weeks before screening. * Malignancy within the last 5 years, with the exception of curable cancer that has received adequate treatment. * Evidence of any unstable or untreated, clinically significant disease or condition that, in the opinion of the Investigator, might confound the interpretation of the study or place the subject at increased risk. * Treatment with high dose corticosteroids, cytotoxic agents, unapproved IPF targeted therapy, and cytokine modulating agents within 8 weeks or 5 half-lives (whichever is longer) before screening * Participation in an investigational study with the last dose of investigational product occurring within 8 weeks or 5 half-lives (whichever is longer) before screening. * Pregnant or breastfeeding. * Medical history of infection with HIV, hepatitis B, or hepatitis C. * History of alcohol abuse and/or dependence within the last 2 years. * History within the last 2 years of significant mental illness, or physical dependence on any opioid or illicit drugs. Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Discontinuing Study Treatment Due to TEAEs | Change in the incidence and severity of adverse events related to study treatment from baseline to 24 weeks | The number of participants with TEAEs leading to discontinuation from the study treatment. The Safety Population (including all participants who received at least one dose of study treatment) is presented. TEAE = treatment-emergent adverse event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Decline in FVC From Baseline to Week 24 | Baseline to Week 24 | Slope in FVC from Baseline to Week 24 (measured in L/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. FVC = forced vital capacity |
| Rate of Decline in ppFVC From Baseline to Week 24 | Baseline to Week 24 | Slope in ppFVC from Baseline to Week 24 (measured in %/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. ppFVC = percent predicted forced vital capacity |
| Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Baseline to Week 24 | Absolute and Relative Change in FVC (L) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity |
| Percent Change in FVC From Baseline to Week 24 | Baseline to Week 24 | Percent Change in FVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity |
| Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Baseline to Week 24 | Absolute and Relative Change in ppFVC (%) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity |
| Summary of Study Treatment Response of FVC | Baseline to Visit 14 (Day 169) | Proportion of participants with an FVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, more than 5% to less than or equal to 10%, and more than 10% at Visit 14 (Day 169). Participants with an FVC response were defined as improvement in FVC (ie, FVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity |
| Summary of Study Treatment Response of ppFVC | Baseline to Visit 14 (Day 169) | Proportion of participants with an ppFVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, greater than 5% to less than or equal to 10%, and greater than 10% at Visit 14 (Day 169). Participants with an ppFVC response were defined as improvement in ppFVC (ie, ppFVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity |
| Percent Change in ppFVC From Baseline to Week 24 | Baseline to Week 24 | Percent Change in ppFVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity |
| Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline to Week 24 | Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature \[Baseline to Week 24\]), as determined by qualitative assessment (central radiologist) and quantitative analysis (Quantitative Lung Fibrosis - QLF analysis). Quantitative HRCT parameters included the following: * Quantitative Lung Fibrosis (QLF) score (% of whole lung field volume) * Ground glass opacity (GGO) (% of whole lung field volume) * Reticulation (% of whole lung field volume) * Honeycombing (% of whole lung field volume) * Normal lung (% of whole lung field volume) * Emphysema (low attenuation area \[LAA\]; % of whole lung field volume) The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. |
| Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline to Visit 14 (Day 169) | Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature \[Baseline to Visit 14 (Day 169)\]), as determined by qualitative assessment (central radiologist). The Likert scale values are included in the descriptions presented. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) with HRCT assessment at Visit 14/Early Termination is presented. |
| Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation | Baseline to study completion, up to Day 239 | Total number of events of participants who experienced idiopathic pulmonary fibrosis (IPF) exacerbation (ie, an unexplained worsening of dyspnea, evidence of hypoxemia as defined by worsened or severely impaired gas exchange, new radiographic alveolar infiltrates, and an absence of an alternative explanation such as infection, pulmonary embolism, pneumothorax, or heart failure) or death (weeks). |
| Events of Hospitalization for Respiratory Ailments or Death | up to 12 weeks after the end of study treatment | Events (participants who experienced hospitalization for respiratory ailments or died) for respiratory ailments are presented. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. |
| Total Events of Death Due to All Causes | up to 12 weeks after the end of study treatment | Rate of mortality due to all causes is presented. Overall survival was defined as the time from start of study treatment to death due to any cause. |
| Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation | Baseline to 12 weeks after end of study treatment | Events of deterioration of Idiopathic Pulmonary Fibrosis (IPF) resulting in lung transplantation (LP; up to 12 weeks after the end of study treatment) or death (weeks) and rate of deterioration of IPF resulting in lung transplantation (up to 12 weeks after the end of study treatment) are presented. Total events = Participants who experience deterioration of IPF resulting in LP (or died). Rate of Deterioration = Rate of Deterioration of IPF Resulting in LP. |
| Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Baseline to Week 24 | Change in diffusion capacity of the lung for carbon monoxide (DLCO) and DLCO corrected for hemoglobin (mL/min/mmHg) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. |
Countries
Germany, Japan, United Kingdom, United States
Participant flow
Recruitment details
Diagnosis of idiopathic pulmonary fibrosis within 5 years before Visit 1a, confirmed by the Principal Investigator (PI) using American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines
Participants by arm
| Arm | Count |
|---|---|
| Placebo Intravenous placebo infusion every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses. | 42 |
| ND-L02-s0201 45 mg ND-L02-s0201: 45 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses. | 41 |
| ND-L02-s0201 90 mg ND-L02-s0201: 90 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses. | 40 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 4 |
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Terminated Early from the Study due to COVID-19 Impact | 9 | 6 | 7 |
Baseline characteristics
| Characteristic | ND-L02-s0201 45 mg | Total | Placebo | ND-L02-s0201 90 mg |
|---|---|---|---|---|
| Age, Continuous | 68.9 years STANDARD_DEVIATION 6.22 | 68.9 years STANDARD_DEVIATION 6.25 | 68.7 years STANDARD_DEVIATION 6.16 | 69.2 years STANDARD_DEVIATION 6.53 |
| Background Standard of Care Nintedanib | 17 Participants | 50 Participants | 17 Participants | 16 Participants |
| Background Standard of Care None | 10 Participants | 30 Participants | 10 Participants | 10 Participants |
| Background Standard of Care Pirfenidone | 14 Participants | 43 Participants | 15 Participants | 14 Participants |
| Baseline Diffusion Capacity of the Lung for Carbon Monoxide Corrected for Hemoglobin | 12.972 mL/min/mmHg STANDARD_DEVIATION 3.6453 | 12.647 mL/min/mmHg STANDARD_DEVIATION 3.6223 | 12.574 mL/min/mmHg STANDARD_DEVIATION 3.9023 | 12.391 mL/min/mmHg STANDARD_DEVIATION 3.3503 |
| Baseline Forced Expiratory Volume in 1 second | 2.380 litres STANDARD_DEVIATION 0.5345 | 2.308 litres STANDARD_DEVIATION 0.5592 | 2.270 litres STANDARD_DEVIATION 0.5603 | 2.274 litres STANDARD_DEVIATION 0.589 |
| Baseline Forced Vital Capacity | 3.012 litres STANDARD_DEVIATION 0.6866 | 2.921 litres STANDARD_DEVIATION 0.7188 | 2.861 litres STANDARD_DEVIATION 0.7214 | 2.890 litres STANDARD_DEVIATION 0.7562 |
| Baseline Hemoglobin Corrected percent predicted DLCO | 53.739 % of normal DLCO STANDARD_DEVIATION 13.1901 | 52.471 % of normal DLCO STANDARD_DEVIATION 13.5264 | 51.762 % of normal DLCO STANDARD_DEVIATION 14.797 | 51.914 % of normal DLCO STANDARD_DEVIATION 12.6957 |
| Baseline Percent Predicted Forced Expiratory Volume | 81.959 % of normal FEV STANDARD_DEVIATION 14.8182 | 79.190 % of normal FEV STANDARD_DEVIATION 16.8442 | 76.890 % of normal FEV STANDARD_DEVIATION 17.8868 | 78.766 % of normal FEV STANDARD_DEVIATION 17.6653 |
| Baseline Percent Predicted Forced Vital Capacity (%) | 79.319 % of total normal FVC STANDARD_DEVIATION 14.994 | 76.618 % of total normal FVC STANDARD_DEVIATION 16.7595 | 73.943 % of total normal FVC STANDARD_DEVIATION 17.0078 | 76.658 % of total normal FVC STANDARD_DEVIATION 18.127 |
| Baseline Pulse Oximetry (%) | 96.6 % of oxygen saturated hemoglobin STANDARD_DEVIATION 1.99 | 96.7 % of oxygen saturated hemoglobin STANDARD_DEVIATION 2 | 96.5 % of oxygen saturated hemoglobin STANDARD_DEVIATION 2.11 | 96.9 % of oxygen saturated hemoglobin STANDARD_DEVIATION 1.93 |
| Baseline Ratio of Forced Expiratory Volume in 1 second/Forced Vital Capacity | 0.794 ratio STANDARD_DEVIATION 0.0383 | 0.792 ratio STANDARD_DEVIATION 0.0445 | 0.795 ratio STANDARD_DEVIATION 0.0501 | 0.787 ratio STANDARD_DEVIATION 0.045 |
| Body mass index group Normal (18.5 - 24.9) | 11 Participants | 33 Participants | 12 Participants | 10 Participants |
| Body mass index group Obese (30 and above) | 13 Participants | 36 Participants | 15 Participants | 8 Participants |
| Body mass index group Overweight (25 - 29.9) | 17 Participants | 54 Participants | 15 Participants | 22 Participants |
| Body mass index group Underweight (below 18.5) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Body mass index (kg/m^2) | 28.093 kg/m^2 STANDARD_DEVIATION 4.3072 | 28.221 kg/m^2 STANDARD_DEVIATION 4.5151 | 28.765 kg/m^2 STANDARD_DEVIATION 4.7625 | 27.780 kg/m^2 STANDARD_DEVIATION 4.5129 |
| Duration of idiopathic pulmonary fibrosis | 24.678 months STANDARD_DEVIATION 16.3543 | 26.734 months STANDARD_DEVIATION 16.4642 | 28.227 months STANDARD_DEVIATION 17.4342 | 27.272 months STANDARD_DEVIATION 15.7152 |
| Eligibility Criteria Based on high resolution computed tomography Consistent with UIP | 10 Participants | 27 Participants | 6 Participants | 11 Participants |
| Eligibility Criteria Based on high resolution computed tomography Definite UIP | 26 Participants | 78 Participants | 30 Participants | 22 Participants |
| Eligibility Criteria Based on high resolution computed tomography Inconsistent with UIP | 5 Participants | 17 Participants | 5 Participants | 7 Participants |
| Eligibility Criteria Based on high resolution computed tomography Possible UIP | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Eligibility Criteria Based on high resolution computed tomography Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 11 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 112 Participants | 37 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| GAP IPF Stage I (0 to 3 points. This stage has the lowest risk of mortality | 29 Participants | 78 Participants | 24 Participants | 25 Participants |
| GAP IPF Stage II (4 to 5 points. This stage has a moderate risk of mortality) | 11 Participants | 43 Participants | 17 Participants | 15 Participants |
| GAP IPF Stage III (6 to 8 points. This stage has the highest risk of mortality) | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Height | 172.316 centimeters STANDARD_DEVIATION 10.5278 | 172.085 centimeters STANDARD_DEVIATION 8.8564 | 172.399 centimeters STANDARD_DEVIATION 6.5281 | 171.519 centimeters STANDARD_DEVIATION 9.2947 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 24 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 29 Participants | 94 Participants | 34 Participants | 31 Participants |
| Risk of Mortality at 1-year | 12.584 risk ratio STANDARD_DEVIATION 4.9287 | 13.753 risk ratio STANDARD_DEVIATION 6.1532 | 14.726 risk ratio STANDARD_DEVIATION 7.157 | 13.930 risk ratio STANDARD_DEVIATION 6.0984 |
| Risk of Mortality at 2-year | 24.922 risk ratio STANDARD_DEVIATION 9.0103 | 26.897 risk ratio STANDARD_DEVIATION 10.9697 | 28.505 risk ratio STANDARD_DEVIATION 12.5204 | 27.233 risk ratio STANDARD_DEVIATION 11.0164 |
| Risk of Mortality at 3-year | 36.014 risk ratio STANDARD_DEVIATION 11.9575 | 38.418 risk ratio STANDARD_DEVIATION 14.2311 | 40.335 risk ratio STANDARD_DEVIATION 15.9727 | 38.869 risk ratio STANDARD_DEVIATION 14.4372 |
| Sex: Female, Male Female | 7 Participants | 18 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 34 Participants | 105 Participants | 37 Participants | 34 Participants |
| Smoking History No | 14 Participants | 44 Participants | 16 Participants | 14 Participants |
| Smoking History Yes | 27 Participants | 79 Participants | 26 Participants | 26 Participants |
| Weight | 84.234 kilograms STANDARD_DEVIATION 19.0174 | 84.050 kilograms STANDARD_DEVIATION 17.3109 | 85.579 kilograms STANDARD_DEVIATION 15.4326 | 82.255 kilograms STANDARD_DEVIATION 17.6139 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 42 | 1 / 41 | 0 / 40 |
| other Total, other adverse events | 35 / 42 | 37 / 41 | 37 / 40 |
| serious Total, serious adverse events | 9 / 42 | 4 / 41 | 6 / 40 |
Outcome results
Primary
Number of Participants Discontinuing Study Treatment Due to TEAEs
The number of participants with TEAEs leading to discontinuation from the study treatment. The Safety Population (including all participants who received at least one dose of study treatment) is presented. TEAE = treatment-emergent adverse event
Time frame: Change in the incidence and severity of adverse events related to study treatment from baseline to 24 weeks
Population: Safety Population (includes all participants who received at least one dose of study treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Discontinuing Study Treatment Due to TEAEs | 1 Participants |
| ND-L02-s0201 45 mg | Number of Participants Discontinuing Study Treatment Due to TEAEs | 3 Participants |
| ND-L02-s0201 90 mg | Number of Participants Discontinuing Study Treatment Due to TEAEs | 4 Participants |
Secondary
Absolute and Relative Change in FVC (L) From Baseline to Week 24
Absolute and Relative Change in FVC (L) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity
Time frame: Baseline to Week 24
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Week 24 FVC (L) | 2.7946 litres | Standard Error 0.10946 |
| Placebo | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Baseline FVC (L) | 2.8754 litres | Standard Error 0.11079 |
| Placebo | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Change from Baseline to Week 24 in FVC (L) | -0.0808 litres | Standard Error 0.03425 |
| ND-L02-s0201 45 mg | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Week 24 FVC (L) | 2.8438 litres | Standard Error 0.11144 |
| ND-L02-s0201 45 mg | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Baseline FVC (L) | 3.0242 litres | Standard Error 0.11207 |
| ND-L02-s0201 45 mg | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Change from Baseline to Week 24 in FVC (L) | -0.1805 litres | Standard Error 0.03668 |
| ND-L02-s0201 90 mg | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Baseline FVC (L) | 2.9032 litres | Standard Error 0.11328 |
| ND-L02-s0201 90 mg | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Change from Baseline to Week 24 in FVC (L) | -0.1315 litres | Standard Error 0.03696 |
| ND-L02-s0201 90 mg | Absolute and Relative Change in FVC (L) From Baseline to Week 24 | Week 24 FVC (L) | 2.7717 litres | Standard Error 0.11253 |
Comparison: Change from Baseline to Week 24 in FVC (L) in the 45 mg cohort versus placebop-value: 0.04995% CI: [-0.1988, -0.0005]random coefficient model
Comparison: Change from Baseline to Week 24 in FVC (L) in the 90 mg cohort versus placebop-value: 0.31695% CI: [-0.1502, 0.0489]random coefficient model
Secondary
Absolute and Relative Change in ppFVC (%) From Baseline to Week 24
Absolute and Relative Change in ppFVC (%) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity
Time frame: Baseline to Week 24
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Week 24 ppFVC | 72.2552 percent | Standard Error 2.58376 |
| Placebo | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Baseline ppFVC | 74.5701 percent | Standard Error 2.54894 |
| Placebo | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Change from Baseline to Week 24 in ppFVC | -2.3149 percent | Standard Error 0.89678 |
| ND-L02-s0201 45 mg | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Week 24 ppFVC | 75.3849 percent | Standard Error 2.63382 |
| ND-L02-s0201 45 mg | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Baseline ppFVC | 79.8896 percent | Standard Error 2.57837 |
| ND-L02-s0201 45 mg | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Change from Baseline to Week 24 in ppFVC | -4.5046 percent | Standard Error 0.96141 |
| ND-L02-s0201 90 mg | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Baseline ppFVC | 77.2260 percent | Standard Error 2.60623 |
| ND-L02-s0201 90 mg | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Change from Baseline to Week 24 in ppFVC | -3.2652 percent | Standard Error 0.96873 |
| ND-L02-s0201 90 mg | Absolute and Relative Change in ppFVC (%) From Baseline to Week 24 | Week 24 ppFVC | 73.9607 percent | Standard Error 2.65995 |
Comparison: Change from baseline to Week 24 in ppFVCp-value: 0.09895% CI: [-4.7869, 0.4075]random coefficient model
Comparison: Change from Baseline to Week 24 in ppFVCp-value: 0.47395% CI: [-3.5579, 1.6573]random coefficient model
Secondary
Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24
Change in diffusion capacity of the lung for carbon monoxide (DLCO) and DLCO corrected for hemoglobin (mL/min/mmHg) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented.
Time frame: Baseline to Week 24
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Baseline DLCO Corrected for Hemoglobin (mL/min/mmHg) | 12.6709 mL/min/mmHg | Standard Error 0.56489 |
| Placebo | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Week 24 DLCO Corrected for Hemoglobin (mL/min/mmHg) | 11.7541 mL/min/mmHg | Standard Error 0.58748 |
| Placebo | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Change from Baseline to Week 24 in DLCO Corrected for Hemoglobin (mL/min/mmHg) | -0.9169 mL/min/mmHg | Standard Error 0.2695 |
| Placebo | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Baseline DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | 12.4411 mL/min/mmHg | Standard Error 0.55897 |
| Placebo | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Week 24 DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | 11.5720 mL/min/mmHg | Standard Error 0.57137 |
| Placebo | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Change from Baseline to Week 24 in DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | -0.8691 mL/min/mmHg | Standard Error 0.26307 |
| ND-L02-s0201 45 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Change from Baseline to Week 24 in DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | -0.7551 mL/min/mmHg | Standard Error 0.27406 |
| ND-L02-s0201 45 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Baseline DLCO Corrected for Hemoglobin (mL/min/mmHg) | 13.0723 mL/min/mmHg | Standard Error 0.57141 |
| ND-L02-s0201 45 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Baseline DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | 12.9860 mL/min/mmHg | Standard Error 0.56543 |
| ND-L02-s0201 45 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Week 24 DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | 12.2308 mL/min/mmHg | Standard Error 0.58226 |
| ND-L02-s0201 45 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Week 24 DLCO Corrected for Hemoglobin (mL/min/mmHg) | 12.3015 mL/min/mmHg | Standard Error 0.59845 |
| ND-L02-s0201 45 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Change from Baseline to Week 24 in DLCO Corrected for Hemoglobin (mL/min/mmHg) | -0.7708 mL/min/mmHg | Standard Error 0.28085 |
| ND-L02-s0201 90 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Week 24 DLCO Corrected for Hemoglobin (mL/min/mmHg) | 12.2669 mL/min/mmHg | Standard Error 0.6046 |
| ND-L02-s0201 90 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Change from Baseline to Week 24 in DLCO Corrected for Hemoglobin (mL/min/mmHg) | -0.2131 mL/min/mmHg | Standard Error 0.28408 |
| ND-L02-s0201 90 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Change from Baseline to Week 24 in DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | -0.3131 mL/min/mmHg | Standard Error 0.27721 |
| ND-L02-s0201 90 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Baseline DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | 12.3792 mL/min/mmHg | Standard Error 0.57155 |
| ND-L02-s0201 90 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Baseline DLCO Corrected for Hemoglobin (mL/min/mmHg) | 12.4800 mL/min/mmHg | Standard Error 0.57759 |
| ND-L02-s0201 90 mg | Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24 | Week 24 DLCO Not Corrected for Hemoglobin (mL/min/mmHg) | 12.0661 mL/min/mmHg | Standard Error 0.58804 |
Comparison: Change from Baseline to Week 24 in DLCO Corrected for Hemoglobin (mL/min/mmHg) in the 45 mg cohort versus placebop-value: 0.70895% CI: [-0.6226, 0.9147]random coefficient
Comparison: Change from Baseline to Week 24 in DLCO Corrected for Hemoglobin (mL/min/mmHg) in the 90 mg cohort versus placebop-value: 0.07495% CI: [-0.0695, 1.4771]random coefficient
Comparison: Change from Baseline to Week 24 in DLCO Not Corrected for Hemoglobin (mL/min/mmHg) in the 45 mg cohort versus placebop-value: 0.76595% CI: [-0.6362, 0.8641]random coefficient model
Comparison: Change from Baseline to Week 24 in DLCO Not Corrected for Hemoglobin (mL/min/mmHg) in the 90 mg cohort versus placebop-value: 0.14895% CI: [-0.1986, 1.3107]random coefficient model
Secondary
Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation
Events of deterioration of Idiopathic Pulmonary Fibrosis (IPF) resulting in lung transplantation (LP; up to 12 weeks after the end of study treatment) or death (weeks) and rate of deterioration of IPF resulting in lung transplantation (up to 12 weeks after the end of study treatment) are presented. Total events = Participants who experience deterioration of IPF resulting in LP (or died). Rate of Deterioration = Rate of Deterioration of IPF Resulting in LP.
Time frame: Baseline to 12 weeks after end of study treatment
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation | Total events to Deterioration of IPF Resulting in LP or Death: | 3 events |
| Placebo | Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation | Rate of Deterioration of IPF Resulting in LP: Total Events | 2 events |
| ND-L02-s0201 45 mg | Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation | Total events to Deterioration of IPF Resulting in LP or Death: | 1 events |
| ND-L02-s0201 45 mg | Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation | Rate of Deterioration of IPF Resulting in LP: Total Events | 0 events |
| ND-L02-s0201 90 mg | Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation | Total events to Deterioration of IPF Resulting in LP or Death: | 0 events |
| ND-L02-s0201 90 mg | Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation | Rate of Deterioration of IPF Resulting in LP: Total Events | 0 events |
Comparison: Rate of Deterioration of IPF Resulting in Lung Transplantation (%) in the 45 mg cohort versus placebop-value: 0.49495% CI: [-16.6, 4.6]Fisher Exact
Comparison: Rate of Deterioration of IPF Resulting in Lung Transplantation (%) in the 90 mg cohort versus placebop-value: 0.49495% CI: [-16.2, 4.5]Fisher Exact
Secondary
Events of Hospitalization for Respiratory Ailments or Death
Events (participants who experienced hospitalization for respiratory ailments or died) for respiratory ailments are presented. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented.
Time frame: up to 12 weeks after the end of study treatment
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Events of Hospitalization for Respiratory Ailments or Death | 5 events |
| ND-L02-s0201 45 mg | Events of Hospitalization for Respiratory Ailments or Death | 3 events |
| ND-L02-s0201 90 mg | Events of Hospitalization for Respiratory Ailments or Death | 3 events |
Comparison: Rate of Hospitalization for Respiratory Ailments (%) in the 45 mg cohort versus placebop-value: 0.71395% CI: [-19.2, 9.6]Fisher Exact
Comparison: Rate of Hospitalization for Respiratory Ailments (%) in the 90 mg cohort versus placebop-value: 0.71395% CI: [-19.2, 10.7]Fisher Exact
Secondary
Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation
Total number of events of participants who experienced idiopathic pulmonary fibrosis (IPF) exacerbation (ie, an unexplained worsening of dyspnea, evidence of hypoxemia as defined by worsened or severely impaired gas exchange, new radiographic alveolar infiltrates, and an absence of an alternative explanation such as infection, pulmonary embolism, pneumothorax, or heart failure) or death (weeks).
Time frame: Baseline to study completion, up to Day 239
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation | 7 events |
| ND-L02-s0201 45 mg | Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation | 3 events |
| ND-L02-s0201 90 mg | Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation | 4 events |
Comparison: Time to First IPF Exacerbation or Death (weeks) in the 45 mg cohort versus placebop-value: 0.51795% CI: [0.189, 2.225]Log Rank
Comparison: Time to First IPF Exacerbation or Death (weeks) in the 90 mg cohort versus placebop-value: 0.50695% CI: [0.198, 2.324]Log Rank
Comparison: Rate of First IPF Exacerbation (%) in the 45 mg cohort versus placebop-value: 0.31395% CI: [-25.2, 5.5]Fisher Exact
Comparison: Rate of First IPF Exacerbation (%) in the 90 mg cohort versus placebop-value: 0.37695% CI: [-22.6, 9.2]Chi-squared
Secondary
Percent Change in FVC From Baseline to Week 24
Percent Change in FVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity
Time frame: Baseline to Week 24
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in FVC From Baseline to Week 24 | -3.10 percentage | Standard Error 4.793 |
| ND-L02-s0201 45 mg | Percent Change in FVC From Baseline to Week 24 | -5.64 percentage | Standard Error 4.488 |
| ND-L02-s0201 90 mg | Percent Change in FVC From Baseline to Week 24 | -4.23 percentage | Standard Error 4.723 |
p-value: 0.66895% CI: [-17.59, 11.28]random coefficient model
p-value: 0.82195% CI: [-16.57, 13.13]random coefficient model
Secondary
Percent Change in ppFVC From Baseline to Week 24
Percent Change in ppFVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity
Time frame: Baseline to Week 24
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in ppFVC From Baseline to Week 24 | -3.10 percentage | Standard Error 4.793 |
| ND-L02-s0201 45 mg | Percent Change in ppFVC From Baseline to Week 24 | -5.64 percentage | Standard Error 4.488 |
| ND-L02-s0201 90 mg | Percent Change in ppFVC From Baseline to Week 24 | -4.23 percentage | Standard Error 4.723 |
p-value: 0.795% CI: [-15.4, 10.34]random coefficient model
p-value: 0.86795% CI: [-14.31, 12.07]random coefficient model
Secondary
Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT
Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature \[Baseline to Visit 14 (Day 169)\]), as determined by qualitative assessment (central radiologist). The Likert scale values are included in the descriptions presented. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) with HRCT assessment at Visit 14/Early Termination is presented.
Time frame: Baseline to Visit 14 (Day 169)
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization) with HRCT assessment at Visit 14/Early Termination
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Same (3) | 28 Participants |
| Placebo | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Much better (5) | 0 Participants |
| Placebo | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Worse (2) | 6 Participants |
| Placebo | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Unknown | 0 Participants |
| Placebo | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Better (4) | 0 Participants |
| Placebo | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Much worse (1) | 3 Participants |
| ND-L02-s0201 45 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Better (4) | 0 Participants |
| ND-L02-s0201 45 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Much better (5) | 0 Participants |
| ND-L02-s0201 45 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Same (3) | 26 Participants |
| ND-L02-s0201 45 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Worse (2) | 3 Participants |
| ND-L02-s0201 45 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Much worse (1) | 1 Participants |
| ND-L02-s0201 45 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Unknown | 0 Participants |
| ND-L02-s0201 90 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Better (4) | 1 Participants |
| ND-L02-s0201 90 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Unknown | 0 Participants |
| ND-L02-s0201 90 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Much worse (1) | 2 Participants |
| ND-L02-s0201 90 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Same (3) | 28 Participants |
| ND-L02-s0201 90 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Much better (5) | 0 Participants |
| ND-L02-s0201 90 mg | Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Worse (2) | 3 Participants |
p-value: 0.256Wilcoxon (Mann-Whitney)
p-value: 0.241Wilcoxon (Mann-Whitney)
Secondary
Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT
Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature \[Baseline to Week 24\]), as determined by qualitative assessment (central radiologist) and quantitative analysis (Quantitative Lung Fibrosis - QLF analysis). Quantitative HRCT parameters included the following: * Quantitative Lung Fibrosis (QLF) score (% of whole lung field volume) * Ground glass opacity (GGO) (% of whole lung field volume) * Reticulation (% of whole lung field volume) * Honeycombing (% of whole lung field volume) * Normal lung (% of whole lung field volume) * Emphysema (low attenuation area \[LAA\]; % of whole lung field volume) The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented.
Time frame: Baseline to Week 24
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in QLF Score (% of whole lung field volume) | 2.28 percentage | Standard Error 1.08 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Reticulation (% of whole lung field volume) | 27.46 percentage | Standard Error 1.89 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Emphysema (% of whole lung field volume) | 9.62 percentage | Standard Error 1.64 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Normal Lung (% of whole lung field volume) | 56.42 percentage | Standard Error 2.287 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Reticulation (% of whole lung field volume) | 28.13 percentage | Standard Error 2.001 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Ground Glass Opacity (% of whole lung field volume) | -0.23 percentage | Standard Error 0.177 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 QLF Score (% of whole lung field volume) | 35.87 percentage | Standard Error 2.195 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Reticulation (% of whole lung field volume) | 0.67 percentage | Standard Error 0.964 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Emphysema (% of whole lung field volume) | 12.08 percentage | Standard Error 1.646 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Normal Lung (% of whole lung field volume) | 58.47 percentage | Standard Error 2.281 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Honeycombing (% of whole lung field volume) | 4.54 percentage | Standard Error 0.861 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Estimation of Normal Lung (% of whole lung field volume) | -2.05 percentage | Standard Error 1.027 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Ground Glass Opacity (% of whole lung field volume) | 5.01 percentage | Standard Error 0.357 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Honeycombing (% of whole lung field volume) | 6.36 percentage | Standard Error 1.018 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Estimation of Emphysema (% of whole lung field volume) | 2.46 percentage | Standard Error 0.936 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Ground Glass Opacity (% of whole lung field volume) | 4.77 percentage | Standard Error 0.358 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Honeycombing (% of whole lung field volume) | 1.81 percentage | Standard Error 0.542 |
| Placebo | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline QLF Score (% of whole lung field volume) | 33.59 percentage | Standard Error 2.189 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Honeycombing (% of whole lung field volume) | 0.61 percentage | Standard Error 0.604 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Normal Lung (% of whole lung field volume) | 64.52 percentage | Standard Error 2.544 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Ground Glass Opacity (% of whole lung field volume) | 4.49 percentage | Standard Error 0.4 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Estimation of Normal Lung (% of whole lung field volume) | -1.17 percentage | Standard Error 1.134 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Emphysema (% of whole lung field volume) | 10.66 percentage | Standard Error 1.829 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Emphysema (% of whole lung field volume) | 9.54 percentage | Standard Error 1.835 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Ground Glass Opacity (% of whole lung field volume) | -0.41 percentage | Standard Error 0.195 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Estimation of Emphysema (% of whole lung field volume) | -1.12 percentage | Standard Error 1.034 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in QLF Score (% of whole lung field volume) | 1.79 percentage | Standard Error 1.194 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Reticulation (% of whole lung field volume) | 23.69 percentage | Standard Error 2.108 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Normal Lung (% of whole lung field volume) | 63.35 percentage | Standard Error 2.549 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Reticulation (% of whole lung field volume) | 24.97 percentage | Standard Error 2.231 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Reticulation (% of whole lung field volume) | 1.28 percentage | Standard Error 1.069 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 QLF Score (% of whole lung field volume) | 29.24 percentage | Standard Error 2.447 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Honeycombing (% of whole lung field volume) | 2.50 percentage | Standard Error 0.961 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Honeycombing (% of whole lung field volume) | 3.11 percentage | Standard Error 1.135 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Ground Glass Opacity (% of whole lung field volume) | 4.91 percentage | Standard Error 0.399 |
| ND-L02-s0201 45 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline QLF Score (% of whole lung field volume) | 27.45 percentage | Standard Error 2.441 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Estimation of Emphysema (% of whole lung field volume) | 0.31 percentage | Standard Error 0.964 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 QLF Score (% of whole lung field volume) | 30.89 percentage | Standard Error 2.258 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Normal Lung (% of whole lung field volume) | 62.68 percentage | Standard Error 2.352 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in QLF Score (% of whole lung field volume) | 3.67 percentage | Standard Error 1.112 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Ground Glass Opacity (% of whole lung field volume) | 4.72 percentage | Standard Error 0.367 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Ground Glass Opacity (% of whole lung field volume) | 4.52 percentage | Standard Error 0.369 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Ground Glass Opacity (% of whole lung field volume) | -0.20 percentage | Standard Error 0.182 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Reticulation (% of whole lung field volume) | 24.03 percentage | Standard Error 1.943 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Reticulation (% of whole lung field volume) | 26.34 percentage | Standard Error 2.062 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Reticulation (% of whole lung field volume) | 2.32 percentage | Standard Error 1.01 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Honeycombing (% of whole lung field volume) | 1.54 percentage | Standard Error 0.886 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Honeycombing (% of whole lung field volume) | 2.37 percentage | Standard Error 1.047 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Honeycombing (% of whole lung field volume) | 0.83 percentage | Standard Error 0.558 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Normal Lung (% of whole lung field volume) | 65.57 percentage | Standard Error 2.343 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline QLF Score (% of whole lung field volume) | 27.22 percentage | Standard Error 2.249 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Change from Baseline to Week 24 in Estimation of Normal Lung (% of whole lung field volume) | -2.88 percentage | Standard Error 1.057 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Baseline Emphysema (% of whole lung field volume) | 8.14 percentage | Standard Error 1.684 |
| ND-L02-s0201 90 mg | Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT | Week 24 Emphysema (% of whole lung field volume) | 8.45 percentage | Standard Error 1.694 |
Comparison: Change from Baseline to Week 24 in QLF Score (% of whole lung field volume) in the 45 mg cohort versus placebop-value: 0.76595% CI: [-3.68, 2.71]random coefficient model
Comparison: Change from Baseline to Week 24 in QLF Score (% of whole lung field volume) in the 90 mg cohort versus placebop-value: 0.3795% CI: [-1.68, 4.47]random coefficient model
Comparison: Change from Baseline to Week 24 in Ground Glass Opacity (% of whole lung field volume) in the 45 mg cohort versus placebop-value: 0.49995% CI: [-0.7, 0.34]random coefficient model
Comparison: Change from Baseline to Week 24 in Ground Glass Opacity (% of whole lung field volume) in the 90 mg cohort versus placebop-value: 0.90195% CI: [-0.47, 0.54]random coefficient model
Comparison: Change from Baseline to Week 24 in Reticulation (% of whole lung field volume) in the 45 mg cohort versus placebop-value: 0.67695% CI: [-2.25, 3.46]random coefficient model
Comparison: Change from Baseline to Week 24 in Reticulation (% of whole lung field volume) in the 90 mg cohort versus placebop-value: 0.24295% CI: [-1.13, 4.42]random coefficient model
Comparison: Change from Baseline to Week 24 in Honeycombing (% of whole lung field volume) in the 45 mg cohort versus placebop-value: 0.1495% CI: [-2.82, 0.4]random coefficient model
Comparison: Change from Baseline to Week 24 in Honeycombing (% of whole lung field volume) in the 90 mg cohort versus placebop-value: 0.21195% CI: [-2.53, 0.56]random coefficient model
Comparison: Change from Baseline to Week 24 in Normal Lung (% of whole lung field volume) in the 45 mg cohort versus placebop-value: 0.56895% CI: [-2.16, 3.91]random coefficient model
Comparison: Change from Baseline to Week 24 in Normal Lung (% of whole lung field volume) in the 90 mg cohort versus placebop-value: 0.57395% CI: [-3.76, 2.09]random coefficient model
Comparison: Change from Baseline to Week 24 in Emphysema (% of whole lung field volume) in the 45 mg cohort versus placebop-value: 0.01295% CI: [-6.35, -0.81]random coefficient model
Comparison: Change from Baseline to Week 24 in Emphysema (% of whole lung field volume) in the 90 mg cohort versus placebop-value: 0.11295% CI: [-4.82, 0.51]random coefficient model
Secondary
Rate of Decline in FVC From Baseline to Week 24
Slope in FVC from Baseline to Week 24 (measured in L/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. FVC = forced vital capacity
Time frame: Baseline to Week 24
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rate of Decline in FVC From Baseline to Week 24 | -0.003366 litres/week | Standard Error 0.0014272 |
| ND-L02-s0201 45 mg | Rate of Decline in FVC From Baseline to Week 24 | -0.007519 litres/week | Standard Error 0.0015285 |
| ND-L02-s0201 90 mg | Rate of Decline in FVC From Baseline to Week 24 | -0.005478 litres/week | Standard Error 0.00154 |
Comparison: Slope in FVC (L/week) in the 45 mg cohort versus placebop-value: 0.04995% CI: [-0.008284, -0.000021]random coefficient model
Comparison: Slope in FVC (L/week) in the 90 mg cohort versus placebop-value: 0.31695% CI: [-0.00626, 0.002036]random coefficient model
Secondary
Rate of Decline in ppFVC From Baseline to Week 24
Slope in ppFVC from Baseline to Week 24 (measured in %/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. ppFVC = percent predicted forced vital capacity
Time frame: Baseline to Week 24
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rate of Decline in ppFVC From Baseline to Week 24 | -0.096455 %/week | Standard Error 0.0373658 |
| ND-L02-s0201 45 mg | Rate of Decline in ppFVC From Baseline to Week 24 | -0.187694 %/week | Standard Error 0.0400588 |
| ND-L02-s0201 90 mg | Rate of Decline in ppFVC From Baseline to Week 24 | -0.136051 %/week | Standard Error 0.0403636 |
p-value: 0.09895% CI: [-0.199456, 0.016979]random coefficient model
p-value: 0.47395% CI: [-0.148248, 0.069056]random coefficient model
Secondary
Summary of Study Treatment Response of FVC
Proportion of participants with an FVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, more than 5% to less than or equal to 10%, and more than 10% at Visit 14 (Day 169). Participants with an FVC response were defined as improvement in FVC (ie, FVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity
Time frame: Baseline to Visit 14 (Day 169)
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization) with FVC assessment at Visit 14
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Summary of Study Treatment Response of FVC | Decline >10% | 3 Participants |
| Placebo | Summary of Study Treatment Response of FVC | Decline >5% to ≤10% | 8 Participants |
| Placebo | Summary of Study Treatment Response of FVC | Improvement | 9 Participants |
| Placebo | Summary of Study Treatment Response of FVC | Decline ≥0% to ≤5% | 10 Participants |
| Placebo | Summary of Study Treatment Response of FVC | Test not done | 12 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of FVC | Decline >5% to ≤10% | 6 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of FVC | Improvement | 7 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of FVC | Decline ≥0% to ≤5% | 6 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of FVC | Decline >10% | 7 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of FVC | Test not done | 15 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of FVC | Test not done | 15 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of FVC | Decline >10% | 4 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of FVC | Improvement | 5 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of FVC | Decline >5% to ≤10% | 6 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of FVC | Decline ≥0% to ≤5% | 10 Participants |
Secondary
Summary of Study Treatment Response of ppFVC
Proportion of participants with an ppFVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, greater than 5% to less than or equal to 10%, and greater than 10% at Visit 14 (Day 169). Participants with an ppFVC response were defined as improvement in ppFVC (ie, ppFVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity
Time frame: Baseline to Visit 14 (Day 169)
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization) with ppFVC assessment at Visit 14
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Summary of Study Treatment Response of ppFVC | Decline >10% | 3 Participants |
| Placebo | Summary of Study Treatment Response of ppFVC | Decline >5% to ≤10% | 8 Participants |
| Placebo | Summary of Study Treatment Response of ppFVC | Improvement | 9 Participants |
| Placebo | Summary of Study Treatment Response of ppFVC | Decline ≥0% to ≤5% | 10 Participants |
| Placebo | Summary of Study Treatment Response of ppFVC | Test not done | 12 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of ppFVC | Decline >5% to ≤10% | 6 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of ppFVC | Improvement | 7 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of ppFVC | Decline ≥0% to ≤5% | 6 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of ppFVC | Decline >10% | 7 Participants |
| ND-L02-s0201 45 mg | Summary of Study Treatment Response of ppFVC | Test not done | 15 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of ppFVC | Test not done | 15 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of ppFVC | Decline >10% | 4 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of ppFVC | Improvement | 5 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of ppFVC | Decline >5% to ≤10% | 6 Participants |
| ND-L02-s0201 90 mg | Summary of Study Treatment Response of ppFVC | Decline ≥0% to ≤5% | 10 Participants |
Secondary
Total Events of Death Due to All Causes
Rate of mortality due to all causes is presented. Overall survival was defined as the time from start of study treatment to death due to any cause.
Time frame: up to 12 weeks after the end of study treatment
Population: ITT Population (include any randomized participants with treatment assignment according to the planned randomization)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Total Events of Death Due to All Causes | 1 Participants |
| ND-L02-s0201 45 mg | Total Events of Death Due to All Causes | 1 Participants |
| ND-L02-s0201 90 mg | Total Events of Death Due to All Causes | 0 Participants |
Comparison: Overall Survival (weeks) in the 45 mg cohort versus placebop-value: 0.937Log Rank
Comparison: Overall Survival (weeks) in the 90 mg cohort versus placebop-value: 0.414Log Rank
Comparison: Rate of Mortality (%) in the 45 mg cohort versus placebop-value: >0.99995% CI: [-10.4, 10.9]Fisher Exact
Comparison: Rate of Mortality (%) in the 90 mg cohort versus placebop-value: >0.99995% CI: [-13.1, 6.8]Fisher Exact