A Study Evaluating the Efficacy and Safety of Vixarelimab in Participants With Idiopathic Pulmonary Fibrosis and in Participants With Systemic Sclerosis-Associated Interstitial Lung Disease

Study Overview
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Brief Summary
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The main purpose of the study is to evaluate the efficacy of vixarelimab compared with placebo on lung function in participants with idiopathic pulmonary fibrosis (IPF) and in participants with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Participants who complete 52-weeks of treatment in the Double-blind Treatment (DBT) period can choose to enroll in the optional Open-label Extension (OLE) period to receive treatment with vixarelimab for another 52 weeks.

Official Title
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A Two-Cohort, Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating the Efficacy and Safety of Vixarelimab Compared With Placebo in Patients With Idiopathic Pulmonary Fibrosis and in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease

Conditions
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Idiopathic Pulmonary Fibrosis, Systemic Sclerosis With Lung Involvement

Intervention / Treatment
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* Drug: Vixarelimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for all Participants: FVC ≥45% predicted during screening as determined by the over-reader Forced expiratory volume in 1 second (FEV1)/FVC ratio >0.70 during screening as determined by the over-reader DLco ≥30% and ≤90% of predicted during screening (Hgb corrected) as determined by the over-reader Minimum 6-MWT distance of 150 m with maximum use of 6 liters per minute (L/min) at sea-level and up to 8 L/min at altitude (> 5000 feet [1524 m] above sea level) of supplemental oxygen while maintaining oxygen saturation of >83% during the 6MWT during screening Participant and investigator consideration of all medicinal treatment options and/or possibly lung transplantation prior to consideration of participation in the study Inclusion Criteria for Cohort 1: Age 40-85 years Documented diagnosis of IPF or IPF (likely) HRCT pattern consistent with the diagnosis of IPF, confirmed by central review of chest HRCT and central review of any available lung biopsy For participants receiving pirfenidone or nintedanib treatment for IPF: treatment for ≥3 months with a stable dose for ≥4 weeks prior to screening and during screening, with plans to continue treatment during the study period Inclusion Criteria for Cohort 2: Age 18-85 years Diagnosis of SSc as defined using the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) criteria HRCT demonstrating ≥10% extent of fibrosis, confirmed by central review of Chest HRCT Evidence of progressive pulmonary fibrosis For participants receiving tocilizumab treatment for SSc-ILD: treatment for ≥3 months with a stable dose for ≥4 weeks prior to screening and during screening, with no contraindications according to local prescribing information, and no intention to change or modify their treatment regimen for the duration of the study Availability of skin for biopsy preferably on proximal forearms having Modified Rodnan Skin Score (mRSS) ≥2 at the biopsy location Inclusion Criteria for OLE Period: - Completion of 52 weeks of treatment in the double-blinded treatment period Exclusion Criteria for all Participants: Percentage of predicted FVC value showing improvement in the 6-month period prior to screening and including screening value Known post-bronchodilator response in FEV1 and/or FVC (defined as an increase by 12% and 200 milliliters [mL]) Resting oxygen saturation of <89% using up to 4 L/min of supplemental oxygen at sea level and up to 6 L/min at altitude (5000 feet [1524 m] above sea level) during screening History of lung transplant Previous treatment with vixarelimab Acute respiratory or systemic bacterial, viral, or fungal infection either during screening or prior to screening not successfully resolved by 4 weeks prior to screening visit Presence of pulmonary hypertension requiring treatment History of malignancy within the 5 years prior to screening Positive hepatitis C virus (HCV) antibody test result accompanied by a positive HCV ribonucleic acid (RNA) test at screening Known immunodeficiency Known evidence of active or untreated latent tuberculosis Exclusion Criteria for Cohort 1: Evidence of other known causes of ILD Emphysema present on ≥50% of the HRCT, or the extent of emphysema is greater than the extent of fibrosis, according to central review of the HRCT Exclusion Criteria for Cohort 2: Evidence of other known causes of ILD Rheumatic autoimmune disease other than SSc Receiving anti-fibrotic treatment (e.g., nintedanib) within 4 weeks prior to screening Exclusion Criteria for OLE Period: Significant non-compliance in the double-blinded treatment period, per investigator's judgment Any new clinically significant pulmonary disease other than IPF or SSc-ILD since enrolling in the double-blinded treatment period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DBT: Cohort 1: Vixarelimab<br>Participants with IPF will receive vixarelimab, subcutaneously (SC), once every two weeks (Q2W) for 52 weeks in the DBT period. | Drug: Vixarelimab<br>* Vixarelimab will be administered as per the schedule specified in the respective arms.<br>* Other names: KPL-716;|
| Placebo Comparator: DBT: Cohort 1: Placebo<br>Participants with IPF will receive vixarelimab matching placebo, SC, Q2W for 52 weeks in the DBT period. | Drug: Placebo<br>* Placebo will be administered as per the schedule specified in the respective arms.<br>|
| Experimental: DBT: Cohort 2: Vixarelimab<br>Participants with SSC-ILD will receive vixarelimab, SC, Q2W for 52 weeks in the DBT period. | Drug: Vixarelimab<br>* Vixarelimab will be administered as per the schedule specified in the respective arms.<br>* Other names: KPL-716;|
| Placebo Comparator: DBT: Cohort 2: Placebo<br>Participants with SSC-ILD will receive vixarelimab matching placebo, SC, Q2W for 52 weeks in the DBT period. | Drug: Placebo<br>* Placebo will be administered as per the schedule specified in the respective arms.<br>|
| Experimental: OLE Period: Cohort 1: Vixarelimab<br>Participants with IPF who complete 52 weeks of treatment in the DBT period can choose to enroll in the OLE period to receive vixarelimab, SC, Q2W for 52 weeks. | Drug: Vixarelimab<br>* Vixarelimab will be administered as per the schedule specified in the respective arms.<br>* Other names: KPL-716;|
| Experimental: OLE Period: Cohort 2: Vixarelimab<br>Participants with SSC-ILD who complete 52 weeks of treatment in the DBT period can choose to enroll in the OLE period to receive vixarelimab, SC, Q2W for 52 weeks. | Drug: Vixarelimab<br>* Vixarelimab will be administered as per the schedule specified in the respective arms.<br>* Other names: KPL-716;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 1 and 2: Absolute Change From Baseline in Forced Vital Capacity (FVC) | FVC is a pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function. | Baseline up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 1 and 2: Absolute Change From Baseline in 6-Minute Walk Test (6MWT) Distance | The 6MWT test is performed indoors on a flat, straight corridor with a hard surface at least 30 meters (m) in length. 6MWT measures the distance a participant is able to walk quickly on a flat, hard surface in a period of 6 minutes. 6MWT measure will be calculated as the simple difference between baseline distance walked over 6 minutes and week 52 distance walked over 6 minutes as measured in meters. | Baseline up to Week 52 | 
| Cohorts 1 and 2: Absolute Change From Baseline in Percentage of Predicted FVC | FVC is a pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function. | Baseline up to Week 52 | 
| Cohorts 1 and 2: Change From Baseline in Diffusion Capacity of the Lung for Carbon Monoxide Adjusted for Hemoglobin (DLco [Hb]) | DLCO measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in the blood. DLCO is adjusted for hemoglobin as small changes in hemoglobin concentration can affect the carbon monoxide transfer. | Baseline up to Week 52 | 
| Cohorts 1 and 2: Time to Disease Progression | Time to disease progression is defined as time to first occurrence of ≥10% absolute decline in percentage of predicted FVC, ≥15% relative decline in 6MWT distance, lung transplantation, or death. FVC=pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function. 6MWT test is performed indoors on a flat, straight corridor with a hard surface at least 30 m in length. 6MWT measures the distance a participant is able to walk quickly on a flat, hard surface in a period of 6 minutes. 6MWT measure will be calculated as the simple difference between baseline distance walked over 6 minutes and week 52 distance walked over 6 minutes as measured in meters. | From the start of study treatment until disease progression or death, whichever occurs first (up to Week 52 of DBT) | 
| Cohorts 1 and 2: Time to First Acute Exacerbation of ILD, or Suspected Acute Exacerbation of ILD |  | From the start of study treatment until end of DBT (up to Week 52) | 
| Cohorts 1 and 2: Change From Baseline in Quantitative Lung Fibrosis on High-Resolution Computed Tomography (HRCT) Scan of the Thorax | High-resolution computer tomography (HRCT) is a type of computed tomography (CT) with specific techniques to enhance image resolution. It is used in the diagnosis of various health problems, most commonly for lung disease. These images show cross sections (slices) through the lungs. | Baseline up to Week 52 | 
| Cohorts 1 and 2: Percentage of Participants with Deaths |  | Up to Week 52 | 
| Cohort 2: Change From Baseline in Skin Sclerosis Assessed Using Modified Rodnan Skin Score (mRSS) | mRSS is a measure of skin thickness. Skin thickness will be assessed by the investigator by palpation across 17 different body sites and scored on a scale of 0 (normal) to 3 (severe skin thickening). The total score is the sum of the individual skin scores from all of these sites and ranges from 0 (normal) to 51 (severe thickening in all 17 areas) units. Higher scores indicate disease worsening. | Baseline up to Week 52 | 
| Cohorts 1 and 2: Change From Baseline in Health-Related Quality of Life (HRQoL) Measured Using King's Brief Interstitial Lung Disease (K-BILD) Questionnaire | K-BILD is a questionnaire that assesses HRQoL in ILDs. It consists of 15 items grouped into psychological, breathlessness and activity, and chest symptom domains, each scored individually on a 7-point scale, with domain-level and total scores transformed 0-100, with higher scores indicating better quality of life. It uses a 2-week recall period. | Baseline up to Week 52 | 
| Cohorts 1 and 2: Change From Baseline in Cough Measured Using Living with Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score | The L-PF symptoms module is a 23-item tool with domains capturing shortness of breath, cough, and energy symptoms using a 0-4 numeric response scale (NRS) response format and a 24-hour recall period. The cough scores ranges from 0 to 100 with higher scores indicating greater symptom burden/impairment. | Baseline up to Week 52 | 
| Cohorts 1 and 2: Change From Baseline in Dyspnea Measured Using L-PF Symptoms Dyspnea Domain Score | The L-PF symptoms module is a 23-item tool with domains capturing shortness of breath, cough, and energy symptoms using a 0-4 NRS response format and a 24-hour recall period. L-PF Symptoms Dyspnea Domain score (dyspnea score) ranges from 0 to 100, with higher score indicating greater impairment. | Baseline up to Week 52 | 
| Cohort 2: Change From Baseline in Pruritus Measured Using the Five-Dimension Itch Scale (5-D Itch) Total Score | The 5-D-Itch questionnaire that measures itch and its impact. It consists of 8 items organized into 5 domains (duration, degree, direction, disability, and distribution). Each domain is scored 1 to 5 with a total score ranging from 5 to 25 with higher scores indicating greater itch severity. | Baseline up to Week 52 | 
| Cohorts 1, 2 and OLE Period: Number of Participants With Adverse Events (AEs) |  | Up to Week 52 | 
| Cohorts 1 and 2: Serum Concentration of Vixarelimab |  | Baseline up to Week 52 | 
| Cohorts 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Vixarelimab |  | Baseline up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Sclerosis-Associated Interstitial Lung Disease