Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis
Brief summary
HZNP-HZN-825-303 (HARBOR) comprises of 2 parts. Part 1 (Core Phase) is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial to evaluate the efficacy, safety and tolerability of HZN-825 in participants with Idiopathic Pulmonary Fibrosis (IPF). Part 2 (Extension Phase) is an optional, open-label, repeat-dose, multicenter extension of the Core Phase. The trial will include up to an 8-week Screening Period and a 52-week Double-blind Treatment Period in the Core Phase and 52 weeks of open-label HZN-825 treatment in the Extension Phase. During the Core Phase, participants will be screened within 8 weeks prior to the baseline (Day 1) Visit. Approximately 135 participants who meet the trial eligibility criteria will be randomly assigned in a 1:1:1 ratio on Day 1 to receive HZN-825 300 mg QD, HZN-825 300 mg BID or matching placebo orally for 52 weeks using the following 2 stratification factors: 1. Concomitant use of approved IPF therapy (i.e., nintedanib or pirfenidone): yes or no 2. Forced vital capacity (FVC) % predicted at Baseline: ≥70% or \<70% Participants who complete the 52-week Double blind Treatment Period of the Core Phase of the trial will be invited to extend their participation in the 52-week Extension Phase of the trial.
Detailed description
Part 1 (Core Phase) The overall objective of the Core Phase is to investigate the efficacy, safety and tolerability of 2 dose regimens of HZN-825, a selective antagonist of lysophosphatidic acid receptor-1 (LPAR1), administered orally once daily (QD) or twice daily (BID) for 52 weeks in the treatment of participants with IPF. Part 2 (Extension Phase) The overall objective of the Extension Phase is to investigate the long-term efficacy, safety and tolerability of HZN-825, a selective antagonist of LPAR1, administered at a dose of 300 mg BID orally to participants with IPF in a 52-week open-label extension (OLE) following completion of the Core Phase of the trial. The dose for the Extension Phase may be modified based on the results of the Core Phase. Two types of Baseline are defined for the Extension Phase: * OLE Baseline, defined as the latest measurement prior to the first dose of HZN-825 in the Extension Phase * HZN-825 Baseline, defined as the latest measurement prior to the first dose of HZN-825 in either the Core Phase or the Extension Phase. For subjects who received placebo in the Core Phase, OLE Baseline will be the same as HZN-825 Baseline. Acquired from Horizon in 2024
Interventions
DRUGHZN-825
Core Phase: Participants will receive HZN-825 300 mg QD, HZN-825 300 mg BID or matching placebo orally in the morning and evening with a meal for 52 weeks according to randomization schema. Extension Phase: Participants will receive open-label HZN-825 150 mg orally in the morning and evening with a meal for 52 weeks.
DRUGPlacebo
Core Phase: Participants will receive HZN-825 300 mg QD, HZN-825 300 mg BID or matching placebo orally in the morning and evening with a meal for 52 weeks according to randomization schema. Extension Phase: Participants who received matching placebo in the Core Phase will receive open-label HZN-825 150 mg orally in the morning and evening with a meal for 52 weeks.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria in Core Phase: 1. Male or female ≥18 years of age at Screening. 2. Current diagnosis of IPF, as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines and determined by central review; the date of initial diagnosis of IPF should be ≤7 years prior to Screening. 3. No recent changes or planned changes to the dose or regimen for IPF therapy, defined as: * Receiving a stable dose of IPF-approved therapy (i.e., nintedanib or pirfenidone) for a minimum of 3 months prior to Day 1 with no plans to change the background regimen during trial participation, or * Not currently receiving background IPF-approved therapy at Screening (either naïve to IPF-approved therapy or previously discontinued any IPF-approved therapy at least 4 weeks prior to Day 1 or drug-specific, 5 half-lives elimination period if longer than 4 weeks), and with no current plans to restart treatment during trial participation * Participants receiving any additional agent for IPF therapy must be on a stable regimen for at least 3 months prior to Day 1 with no current plans to change the treatment regimen during trial participation. Any previously discontinued therapy used to treat IPF must have been discontinued at least 4 weeks prior to Day 1 or 5 half-lives for that specific therapy must have elapsed, whichever is longer, with no plans to restart the therapy during trial participation. 4. Lung high-resolution computed tomography (HRCT) historically performed within 6 months prior to the Screening Visit and according to the minimum requirements for IPF diagnosis by central review based on participant's HRCT. If an evaluable HRCT is not available within 6 months prior to Screening, an HRCT will be performed at Screening to determine eligibility, according to the same requirements as the historical HRCT. 5. HRCT shows ≥10% to \<50% parenchymal fibrosis (reticulation) and the extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (central reviewer determined). 6. Meets all of the following criteria during the Screening Period: 1. FVC ≥45% predicted of normal 2. forced expiratory volume in 1 second (FEV1)/FVC ≥0.7 3. Diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin is ≥25% and ≤90% predicted of normal 7. Estimated minimum life expectancy of ≥30 months for non-IPF-related disease, in the opinion of the Investigator. 8. Vaccinations are up to date given age, comorbidities and local availability prior to trial drug dosing. 9. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial. Key Inclusion Criteria in Extension Phase: 1. Completed the Double-blind Treatment Period (Week 52) of the Core Phase of the trial; subjects prematurely discontinued from trial drug in the Core Phase of the trial for reasons other than safety or tolerability may be included at the discretion of the Investigator after completing scheduled visits, including Week 52 assessments. 2. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the Extension Phase of the trial. Key
Exclusion criteria
Core Phase: 1. Any of the following cardiovascular diseases: 1. uncontrolled, severe hypertension (≥160/100 mmHg), within 6 months of Screening 2. myocardial infarction within 6 months of Screening 3. unstable cardiac angina within 6 months of Screening 2. Interstitial lung disease (ILD) associated with known primary diseases (e.g., sarcoidosis, amyloidosis and coronavirus disease 2019 \[COVID-19\]), connective tissue disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, Sjogren's, dermatomyositis, scleroderma), exposures (e.g., radiation, silica, asbestos and coal dust) or drugs (e.g., amiodarone). 3. Known active bacterial, viral, fungal, mycobacterial or other infection, including tuberculosis or atypical mycobacterial disease (fungal infections of nail beds are allowed). The participant must be 3 months beyond any acute infection with COVID-19 if there has been a prior infection. 4. Clinically significant pulmonary hypertension requiring chronic medical therapy. 5. Use of any of the following therapies within 4 weeks prior to Screening, during the Screening Period or planned during the trial: prednisone at steady dose \>10 mg/day or equivalent or cyclosporine. Change in regimen or dosage of any immunosuppressant during the Screening Period through the end of trial participation will require consultation with and approval by the trial Medical Monitor. 6. Use of rifampin within 2 weeks prior to Day 1 or planned during the trial. 7. Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ). 8. Women of childbearing potential (WOCBP) or male subjects not agreeing to use highly effective method(s) of birth control throughout the trial and for 4 weeks after last dose of trial drug. Females must refrain from egg/ova donation for 4 weeks after the last dose of trial drug and males must refrain from sperm donation for 3 months after the last dose of trial drug. 9. Pregnant or lactating women and women who plan to become pregnant or breast feed during the trial and within 4 weeks after the last dose of trial drug. 10. Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the subject. 11. Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial. 12. Known history of positive test for human immunodeficiency virus (HIV). 13. Active hepatitis (hepatitis B: positive hepatitis B surface antigen and positive anti-hepatitis B core antibody \[anti-HBcAb\] and negative hepatitis B surface antibody \[HBsAb\] or positive for HBcAb with a positive test for HBsAb and with presence of hepatitis B virus DNA at Screening; hepatitis C: positive anti-hepatitis C virus \[anti-HCV\] and positive RNA HCV). 14. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis. 15. Previous organ transplant (including allogeneic and autologous marrow transplant). 16. International normalized ratio \>2, prolonged prothrombin time \>1.5 × the upper limit of normal (ULN) or partial thromboplastin time \>1.5 × ULN at Screening. 17. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 × ULN. 18. Estimated glomerular filtration rate \<30 mL/min/1.73 m\^2 at Screening. 19. Total bilirubin \>1.5 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is ≤3.0 mg/dL. 20. Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment according to the Child-Pugh scoring system. 21. Any confirmed Grade 3 or higher laboratory abnormality. 22. Any laboratory abnormality at Screening that, in the opinion of the Investigator, would preclude the participant's entry in the trial. 23. Exposure to an experimental drug (with the exception of HZN-825) or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is the longest, prior to Day 1. 24. Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial. Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Phase: Change in FVC % Predicted From Baseline to Week 52 | Baseline and Week 52 | FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height. |
| Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104 | OLE baseline (Week 52) and Week 104 | OLE baseline was defined as the latest measurement prior to the first dose of HZN-825 in the extension phase. FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52 | Baseline and Week 52 | The K-BILD is a self-completed health status questionnaire comprising 15 items and a 7-point Likert response scale that was developed and validated specifically for patients with IPF. This questionnaire has 3 domains: psychological, breathlessness and activities and chest symptoms. The K-BILD domains and total score range from 0 to 100; 100 represents best health status. A positive change from baseline indicates an improvement in symptoms. |
| Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 | Baseline and Week 52 | The L-IPF is a validated questionnaire that assesses symptoms, disease impacts and health-related quality of life in subjects with IPF. This questionnaire was developed with input from the FDA and comprises 2 modules: a 15-item symptom module with 3 domains (dyspnea, cough, and energy), all with a 24-hour recall, and a 20-item impacts module with 1-week recall. Symptoms Total Score and Impacts Total Score were transformed to a model-based scale ranging from 0 to 100 where higher scores indicate greater impairment. |
| Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52 | Baseline to Week 52 | The LCQ is a patient-reported questionnaire evaluating the impact of cough on quality of life. The LCQ comprises 19 items and takes 5 to 10 minutes to complete. Each item assesses symptoms or the impact of symptoms over the last 2 weeks on a 7-point Likert scale. Scores in 3 domains (physical, psychological, and social) are calculated as a mean for each domain (range: 1 to 7). A total score (range: 3 to 21) is also calculated by adding together the domain scores. Higher scores indicate better quality of life and a positive change from baseline indicates an improvement in quality of life. |
| Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52 | Baseline and Week 52 | FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height. |
| Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52 | Up to Week 52 | The time-to-progression was defined as the duration from the date of first dose of study drug to either (a) the date of the visit where FVC % predicted declines ≥ 10% from Baseline or (b) the date of participant death, whichever occurred earlier. Results were given based on the Kaplan-Meier reading with a cutoff at Day 365. |
| Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From 1st dose to last dose + 28 days, Median (min, max) duration was 12.0 (1.0, 13.1) months for Core Phase and 7.0 (1.6, 13.2) months for OLE Phase. | A TEAE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE was considered a serious adverse event (SAE) if it resulted in any of the following: death; life-threatening experience; persistent or significant disability or incapacity; inpatient hospitalization or prolongation of hospitalization; congenital anomaly or birth defect; medically important event that may require medical or surgical intervention to prevent one of the outcomes listed. An adverse event of special interest (AESI) was an AE of scientific and medical concern specific to HZN-825. Orthostatic hypotension was considered an AESI. Clinically significant changes in vital signs, electrocardiograms, echocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs. |
| Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Day 1 (2-4 hours after the first dose), Week 4 (pre-dose), Week 10, Weeks 16 and 28 (pre-dose and 2-4 hours post-dose), and Weeks 40 and 52 (pre-dose for participants entering OLE). | Pre- and Post-dose Concentrations of HZN-825 were presented. |
| Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52 | Up to Week 52 | Hospitalization due to respiratory distress was defined as a non-elective hospitalization lasting more than 24 hours in a hospital, emergency room or observation unit, due to respiratory causes that occur after randomization Adverse events identified as leading to hospitalization due to respiratory distress were adjudicated to confirm that the event and hospitalization met the stated criteria. Participants who did not experience a hospitilization event were considered censored. |
| Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52 | Baseline and Week 52 | The 6MWT measures the distance a subject can quickly walk on a flat, hard surface in 6 minutes (6-minute walk distance). This test evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units and muscle metabolism. |
Countries
Argentina, Australia, Canada, Chile, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, Poland, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 153 participants with Idiopathic Pulmonary Fibrosis (IPF) were enrolled in 16 countries between January 2022 and December 2024.
Pre-assignment details
This trial consisted of 2 parts. During part 1 (Core Phase) participants were randomized in 1:1:1 ratio to receive HZN-825 300 mg once daily (QD), twice daily (BID) or placebo, for 52 weeks. Part 2 (Extension Phase) was an optional, open-label extension (OLE) where all participants received HZN-825 BID for 52 weeks. 11 participants who completed part 1 did not enter the part 2.
Participants by arm
| Arm | Count |
|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID In the core phase participants received HZN-825 300 mg QD, for 52 weeks. In the optional OLE phase of the study (Part 2) participants received HZN-825 BID for 52 weeks. | 49 |
| HZN-825 300 mg BID In the core phase participants received HZN-825 300 mg BID, for 52 weeks. In the optional OLE phase of the study (Part 2) participants continued to receive HZN-825 BID for 52 weeks. | 52 |
| Placebo Then HZN-825 300 mg BID In the core phase participants received Placebo for 52 weeks. In the OLE phase of the study (Part 2) participants received HZN-825 BID for 52 weeks. | 52 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1: Core Phase | Adverse Event | 2 | 3 | 0 |
| Part 1: Core Phase | Death | 3 | 4 | 2 |
| Part 1: Core Phase | Lost to Follow-up | 0 | 0 | 1 |
| Part 1: Core Phase | Physician Decision | 0 | 1 | 1 |
| Part 1: Core Phase | Withdrawal by Subject/Guardian | 4 | 6 | 5 |
| Part 2: Extension Phase | Death | 2 | 4 | 5 |
| Part 2: Extension Phase | Physician Decision | 1 | 2 | 0 |
| Part 2: Extension Phase | Study Terminated by Sponsor | 27 | 22 | 27 |
| Part 2: Extension Phase | Withdrawal by Subject/Guardian | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | HZN-825 300 mg QD Then HZN-825 300 mg BID | HZN-825 300 mg BID | Placebo Then HZN-825 300 mg BID | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 35 Participants | 42 Participants | 45 Participants | 122 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 10 Participants | 7 Participants | 31 Participants |
| Age, Continuous | 70.0 years | 73.5 years | 73.0 years | 73.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 16 Participants | 25 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 36 Participants | 27 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Forced Vital Capacity (FVC) percent (FVC %) Predicted at Baseline | 73.23 % predicted FVC STANDARD_DEVIATION 17.074 | 72.11 % predicted FVC STANDARD_DEVIATION 16.558 | 72.66 % predicted FVC STANDARD_DEVIATION 12.761 | 72.66 % predicted FVC STANDARD_DEVIATION 15.456 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 16 Participants | 9 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 35 Participants | 35 Participants | 40 Participants | 110 Participants |
| Sex: Female, Male Female | 25 Participants | 12 Participants | 15 Participants | 52 Participants |
| Sex: Female, Male Male | 24 Participants | 40 Participants | 37 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 49 | 4 / 52 | 2 / 52 | 11 / 110 |
| other Total, other adverse events | 23 / 49 | 33 / 52 | 20 / 52 | 35 / 110 |
| serious Total, serious adverse events | 10 / 49 | 14 / 52 | 9 / 52 | 23 / 110 |
Outcome results
Primary
Core Phase: Change in FVC % Predicted From Baseline to Week 52
FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.
Time frame: Baseline and Week 52
Population: Full Analysis Set (FAS): All participants who were randomized and took at least 1 dose of HZN-825.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Change in FVC % Predicted From Baseline to Week 52 | -4.13 % predicted FVC | Standard Error 1.045 |
| HZN-825 300 mg BID | Core Phase: Change in FVC % Predicted From Baseline to Week 52 | -3.38 % predicted FVC | Standard Error 1.092 |
| Placebo Then HZN-825 300 mg BID | Core Phase: Change in FVC % Predicted From Baseline to Week 52 | -2.99 % predicted FVC | Standard Error 1.025 |
Comparison: The primary analysis was based on a mixed model for repeated measures (MMRM) analysis of covariance (ANCOVA) model using observed change in FVC % predicted values from all planned post-baseline assessments (Weeks 4, 16, 28, 40 and 52) with covariates of treatment group (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), prior use of IPF therapy \[yes or no\], FVC% predicted at baseline \[≥ 70, \<70\], visit week, and treatment by visit week interaction.p-value: 0.438890% CI: [-3.56, 1.29]Mixed Model for Repeated Measures (MMRM)
Comparison: The primary analysis was based on a mixed model for repeated measures (MMRM) analysis of covariance (ANCOVA) model using observed change in FVC % predicted values from all planned post-baseline assessments (Weeks 4, 16, 28, 40 and 52) with covariates of treatment group (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), prior use of IPF therapy \[yes or no\], FVC% predicted at baseline \[≥ 70, \<70\], visit week, and treatment by visit week interaction.p-value: 0.795990% CI: [-2.86, 2.09]MMRM
Primary
Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104
OLE baseline was defined as the latest measurement prior to the first dose of HZN-825 in the extension phase. FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.
Time frame: OLE baseline (Week 52) and Week 104
Population: OLE Phase Analysis Set (OLE-SAF): All participants that were enrolled in OLE Phase and took at least 1 dose of HZN-825 during the OLE Phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104 | 11.38 % predicted FVC | Standard Deviation 23.237 |
| HZN-825 300 mg BID | Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104 | -0.63 % predicted FVC | Standard Deviation 16.283 |
| Placebo Then HZN-825 300 mg BID | Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104 | -2.62 % predicted FVC | Standard Deviation 6.305 |
Secondary
Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52
The K-BILD is a self-completed health status questionnaire comprising 15 items and a 7-point Likert response scale that was developed and validated specifically for patients with IPF. This questionnaire has 3 domains: psychological, breathlessness and activities and chest symptoms. The K-BILD domains and total score range from 0 to 100; 100 represents best health status. A positive change from baseline indicates an improvement in symptoms.
Time frame: Baseline and Week 52
Population: FAS: All participants who were randomized and took at least 1 dose of HZN-825.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52 | -1.5 Score on a scale | Standard Error 1.65 |
| HZN-825 300 mg BID | Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52 | -1.4 Score on a scale | Standard Error 1.67 |
| Placebo Then HZN-825 300 mg BID | Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52 | -0.3 Score on a scale | Standard Error 1.62 |
Comparison: Estimated from a MMRM with unstructured variance-covariance matrix, that included treatment group, time point, treatment by timepoint interaction, and stratification factors as covariates.p-value: 0.609190% CI: [-5, 2.6]MMRM
Comparison: Estimated from a MMRM with unstructured variance-covariance matrix, that included treatment group, time point, treatment by timepoint interaction, and stratification factors as covariates.p-value: 0.637490% CI: [-4.9, 2.7]MMRM
Secondary
Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52
The LCQ is a patient-reported questionnaire evaluating the impact of cough on quality of life. The LCQ comprises 19 items and takes 5 to 10 minutes to complete. Each item assesses symptoms or the impact of symptoms over the last 2 weeks on a 7-point Likert scale. Scores in 3 domains (physical, psychological, and social) are calculated as a mean for each domain (range: 1 to 7). A total score (range: 3 to 21) is also calculated by adding together the domain scores. Higher scores indicate better quality of life and a positive change from baseline indicates an improvement in quality of life.
Time frame: Baseline to Week 52
Population: FAS: All participants who were randomized and took at least 1 dose of HZN-825.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52 | 0.19 Score on a scale | Standard Error 0.463 |
| HZN-825 300 mg BID | Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52 | -0.45 Score on a scale | Standard Error 0.468 |
| Placebo Then HZN-825 300 mg BID | Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52 | 0.54 Score on a scale | Standard Error 0.453 |
Comparison: Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors baseline FVC% predicted, treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\]), visit week, and treatment by visit week interaction.p-value: 0.583290% CI: [-1.42, 0.71]MMRM
Comparison: Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors baseline FVC% predicted, treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\]), visit week, and treatment by visit week interaction.p-value: 0.129790% CI: [-2.06, 0.09]MMRM
Secondary
Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52
The L-IPF is a validated questionnaire that assesses symptoms, disease impacts and health-related quality of life in subjects with IPF. This questionnaire was developed with input from the FDA and comprises 2 modules: a 15-item symptom module with 3 domains (dyspnea, cough, and energy), all with a 24-hour recall, and a 20-item impacts module with 1-week recall. Symptoms Total Score and Impacts Total Score were transformed to a model-based scale ranging from 0 to 100 where higher scores indicate greater impairment.
Time frame: Baseline and Week 52
Population: FAS: All participants who were randomized and took at least 1 dose of HZN-825.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 | L-IPF Symptoms Total Score | 4.0 Score on a scale | Standard Error 1.42 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 | L-IPF Impact Total Score | 3.1 Score on a scale | Standard Error 1.93 |
| HZN-825 300 mg BID | Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 | L-IPF Symptoms Total Score | 2.6 Score on a scale | Standard Error 1.45 |
| HZN-825 300 mg BID | Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 | L-IPF Impact Total Score | 1.3 Score on a scale | Standard Error 1.97 |
| Placebo Then HZN-825 300 mg BID | Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 | L-IPF Symptoms Total Score | 0.6 Score on a scale | Standard Error 1.39 |
| Placebo Then HZN-825 300 mg BID | Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 | L-IPF Impact Total Score | -0.8 Score on a scale | Standard Error 1.9 |
Comparison: Impact Total Score Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors baseline FVC% predicted, treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\]), visit week, and treatment by visit week interaction.p-value: 0.152690% CI: [-0.6, 8.3]MMRM
Comparison: Impact Total Score Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors baseline FVC% predicted, treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\]), visit week, and treatment by visit week interaction.p-value: 0.442190% CI: [-2.4, 6.6]MMRM
Comparison: Symptoms Total Score Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors baseline FVC% predicted, treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\]), visit week, and treatment by visit week interaction.p-value: 0.093690% CI: [0.1, 6.6]MMRM
Comparison: Symptoms Total Score Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors baseline FVC% predicted, treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\]), visit week, and treatment by visit week interaction.p-value: 0.312990% CI: [-1.3, 5.3]MMRM
Secondary
Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52
The 6MWT measures the distance a subject can quickly walk on a flat, hard surface in 6 minutes (6-minute walk distance). This test evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units and muscle metabolism.
Time frame: Baseline and Week 52
Population: FAS: All participants who were randomized and took at least 1 dose of HZN-825.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52 | 14.00 Meters | Standard Error 12.99 |
| HZN-825 300 mg BID | Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52 | -3.95 Meters | Standard Error 13.081 |
| Placebo Then HZN-825 300 mg BID | Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52 | -2.71 Meters | Standard Error 12.757 |
Comparison: Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\], as used in IRT randomization), visit week, and treatment by visit week interaction.p-value: 0.357990% CI: [-13.3, 46.73]MMRM
Comparison: Estimated from a mixed effect repeated measurement analysis with unstructured variance-covariance matrix, that included factors treatment (300 mg HZN-825 QD, 300 mg HZN-825 BID, placebo), the Baseline factors used for stratifying randomization as covariates (prior use of approved IPF therapy \[yes/no\] and Baseline FVC% Predicted \[\>=70, \<70\], as used in IRT randomization), visit week, and treatment by visit week interaction.p-value: 0.94690% CI: [-31.35, 28.88]MMRM
Secondary
Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52
FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.
Time frame: Baseline and Week 52
Population: FAS: All participants who were randomized and took at least 1 dose of HZN-825.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52 | 6 participants |
| HZN-825 300 mg BID | Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52 | 7 participants |
| Placebo Then HZN-825 300 mg BID | Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52 | 4 participants |
Comparison: The percentage of participants with a decrease in FVC% predicted ≥10% from baseline at Week 52 were analyzed with observed data using a stratified logistic regression model. Baseline value and treatment were considered as factors in the model and prior use of approved IPF therapy \[yes or no\], FVC% predicted at baseline \[≥ 70, \<70\] were considered as stratification factors.p-value: 0.717990% CI: [0.417, 1.75]Stratified logistic regression
Comparison: The percentage of participants with a decrease in FVC% predicted ≥10% from baseline at Week 52 were analyzed with observed data using a stratified logistic regression model. Baseline value and treatment were considered as factors in the model and prior use of approved IPF therapy \[yes or no\], FVC% predicted at baseline \[≥ 70, \<70\] were considered as stratification factors.p-value: 0.070690% CI: [0.236, 0.934]Stratified logistic regression
Secondary
Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE was considered a serious adverse event (SAE) if it resulted in any of the following: death; life-threatening experience; persistent or significant disability or incapacity; inpatient hospitalization or prolongation of hospitalization; congenital anomaly or birth defect; medically important event that may require medical or surgical intervention to prevent one of the outcomes listed. An adverse event of special interest (AESI) was an AE of scientific and medical concern specific to HZN-825. Orthostatic hypotension was considered an AESI. Clinically significant changes in vital signs, electrocardiograms, echocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs.
Time frame: From 1st dose to last dose + 28 days, Median (min, max) duration was 12.0 (1.0, 13.1) months for Core Phase and 7.0 (1.6, 13.2) months for OLE Phase.
Population: Safety analysis set: all participants who took any dose of study drug during the Core Phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: TEAEs | 38 Participants |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: SAEs | 10 Participants |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: AESIs | 1 Participants |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: TEAEs | 27 Participants |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: SAEs | 8 Participants |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: AESIs | 0 Participants |
| HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: SAEs | 14 Participants |
| HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: TEAEs | 22 Participants |
| HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: AESIs | 1 Participants |
| HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: TEAEs | 42 Participants |
| HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: AESIs | 2 Participants |
| HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: SAEs | 6 Participants |
| Placebo Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: SAEs | 9 Participants |
| Placebo Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: SAEs | 9 Participants |
| Placebo Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: AESIs | 1 Participants |
| Placebo Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: AESIs | 0 Participants |
| Placebo Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Core Phase: TEAEs | 38 Participants |
| Placebo Then HZN-825 300 mg BID | Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Extension Phase: TEAEs | 33 Participants |
Secondary
Core Phase: Pre- and Post-dose Concentrations of HZN-825
Pre- and Post-dose Concentrations of HZN-825 were presented.
Time frame: Day 1 (2-4 hours after the first dose), Week 4 (pre-dose), Week 10, Weeks 16 and 28 (pre-dose and 2-4 hours post-dose), and Weeks 40 and 52 (pre-dose for participants entering OLE).
Population: Pharmacokinetic analysis set: all randomized participants who took at least 1 dose of HZN-825 and have at least 1 nonmissing postdose concentration value reported by the PK laboratory.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 40 (Pre-dose) | 8487.6 ng/mL | Standard Deviation 9209.61 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Day 1 (Post-dose) | 16676.2 ng/mL | Standard Deviation 11030.3 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 4 (Pre-dose) | 6521.3 ng/mL | Standard Deviation 7756.18 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 10 | 11372.8 ng/mL | Standard Deviation 11123.02 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 16 (Pre-dose) | 5296.4 ng/mL | Standard Deviation 3093.68 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 16 (Post-dose) | 21162.9 ng/mL | Standard Deviation 11543.77 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 28 (Pre-dose) | 5435.8 ng/mL | Standard Deviation 4125.22 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 28 (Post-dose) | 19410.7 ng/mL | Standard Deviation 13812.87 |
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 52 (Pre-dose) | 5030.2 ng/mL | Standard Deviation 3998.99 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 28 (Post-dose) | 27598.4 ng/mL | Standard Deviation 13634.06 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 16 (Post-dose) | 24629.3 ng/mL | Standard Deviation 11871.17 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Day 1 (Post-dose) | 16209.4 ng/mL | Standard Deviation 11592.69 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 40 (Pre-dose) | 20702.0 ng/mL | Standard Deviation 13362.76 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 4 (Pre-dose) | 18360.0 ng/mL | Standard Deviation 11953.98 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 28 (Pre-dose) | 19258.1 ng/mL | Standard Deviation 10368.1 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 10 | 23807.8 ng/mL | Standard Deviation 13864.61 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 52 (Pre-dose) | 17330.1 ng/mL | Standard Deviation 10638.75 |
| HZN-825 300 mg BID | Core Phase: Pre- and Post-dose Concentrations of HZN-825 | Week 16 (Pre-dose) | 16889.8 ng/mL | Standard Deviation 9952.2 |
Secondary
Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52
Hospitalization due to respiratory distress was defined as a non-elective hospitalization lasting more than 24 hours in a hospital, emergency room or observation unit, due to respiratory causes that occur after randomization Adverse events identified as leading to hospitalization due to respiratory distress were adjudicated to confirm that the event and hospitalization met the stated criteria. Participants who did not experience a hospitilization event were considered censored.
Time frame: Up to Week 52
Population: FAS: All participants who were randomized and took at least 1 dose of HZN-825, inclusive of censoring.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52 | NA Days |
| HZN-825 300 mg BID | Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52 | NA Days |
| Placebo Then HZN-825 300 mg BID | Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52 | NA Days |
Comparison: Estimated from a stratified Cox proportional hazards regression model stratified by prior use of approved IPF therapy \[yes or no\] and FVC% predicted at baseline \[= 70, \<70\] and treatment group as factor. Placebo group is the reference group for the analysis.p-value: 0.999690% CI: [0.34, 2.9]Regression, Cox
Comparison: Estimated from a stratified Cox proportional hazards regression model stratified by prior use of approved IPF therapy \[yes or no\] and FVC% predicted at baseline \[= 70, \<70\] and treatment group as factor. Placebo group is the reference group for the analysis.p-value: 0.372190% CI: [0.66, 4.48]Regression, Cox
Secondary
Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52
The time-to-progression was defined as the duration from the date of first dose of study drug to either (a) the date of the visit where FVC % predicted declines ≥ 10% from Baseline or (b) the date of participant death, whichever occurred earlier. Results were given based on the Kaplan-Meier reading with a cutoff at Day 365.
Time frame: Up to Week 52
Population: FAS: All participants who were randomized and took at least 1 dose of HZN-825, inclusive of censoring.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HZN-825 300 mg QD Then HZN-825 300 mg BID | Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52 | NA Days |
| HZN-825 300 mg BID | Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52 | NA Days |
| Placebo Then HZN-825 300 mg BID | Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52 | NA Days |
Comparison: Estimated from a stratified Cox proportional hazards regression model stratified by prior use of approved IPF therapy \[yes or no\] and FVC% predicted at baseline \[= 70, \<70\] and treatment group as factor. Placebo group is the reference group for the analysis.p-value: 0.477890% CI: [0.63, 3.32]Regression, Cox
Comparison: Estimated from a stratified Cox proportional hazards regression model stratified by prior use of approved IPF therapy \[yes or no\] and FVC% predicted at baseline \[= 70, \<70\] and treatment group as factor. Placebo group is the reference group for the analysis.p-value: 0.043890% CI: [1.22, 5.61]Regression, Cox