A Phase 2, Randomized Dose-ranging Study to Evaluate the Efficacy of Tralokinumab in Adults With Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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To study the safety and effectiveness of multiple-doses of tralokinumab on pulmonary function in adults with mild to moderate idiopathic pulmonary fibrosis (IPF). IPF is a chronic, progressive, irreversible, and usually fatal lung disease of unknown cause.

Detailed Description
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The primary objective of this study is to determine the effect of multiple doses of tralokinumab on pulmonary function in adults with mild to moderate IPF

Official Title
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A Phase 2, Randomized Dose-ranging Study to Evaluate the Efficacy of Tralokinumab in Adults With Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Biological: Tralokinumab
* Biological: Tralokinumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 1) IPF diagnosis for <= 5 years prior to Visit 1 (screening). Confirmation of diagnosis of IPF in accordance is required for subject inclusion 2) Confirmed diagnosis of IPF by clinical characteristics, HRCT and surgical lung biopsy (if required) 3)Mild to moderate IPF to include all of the following at screening: FVC >= 50% predicted normal Partial pressure of oxygen in arterial blood (PaO2) of >= 55 mmHg on room air or 50 mmHg at high altitude (> 1500 meters), or oxygen saturation by pulse oximetry (SpO2) of >= 90%on room air at rest Hemoglobin-corrected diffusion capacity for carbon monoxide (DLCO) >= 30% predicted normal 4) Be able to walk >= 100 meters unassisted Key Exclusion Criteria: A FEV1/FVC ratio less than 0.70 at the time of screening (postbronchodilator) The extent of emphysema on the HRCT is greater than the extent of fibrosis. Currently listed for lung transplantation Use of the following medications: Immunosuppressive medications (eg, methotrexate, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid) within 3 months prior to Visit 1 (screening). Oral prednisone <= 15 mg/day (or equivalent oral corticosteroid) is allowed for chronic use if subject was on a stable dose at least 30 days prior to Visit 1 (screening) Pirfenidone within 4 weeks prior to Visit 1 (screening) N-acetylcysteine within 4 weeks prior to Visit 1 (screening) Live attenuated vaccines within 4 weeks prior to Visit 1 (screening)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 79 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tralokinumab 400 milligram (mg)<br>Participants will receive Tralokinumab 400 mg intravenous (IV) infusion Q4W for 68 Weeks. | Biological: Tralokinumab<br>* Participants will receive Tralokinumab 400 mg IV infusion Q4W for 68 Weeks.<br>|
| Experimental: Tralokinumab 800 mg<br>Participants will receive Tralokinumab 800 mg IV infusion Q4W for 68 Weeks. | Biological: Tralokinumab<br>* Participants will receive Tralokinumab 800 mg IV infusion Q4W for 68 Weeks.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo IV once every 4 Weeks (Q4W) for 68 Weeks. | Other: Placebo<br>* Participants will receive placebo IV once every 4 Weeks (Q4W) for 68 Weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percent-predicted Forced Vital Capacity (FVC) at Week 52 | Forced vital capacity (FVC) is a standard pulmonary function test used to monitor disease progression in IPF. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received Tralokinumab. Treatment-emergent were events between administration of investigational product and Week 88 that were absent before treatment or that worsened relative to pretreatment state. | From the start of study treatment through Week 88 | 
| Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-emergent Adverse Events | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent were events between administration of investigational product and Week 88 that were absent before treatment or that worsened relative to pre-treatment state. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed. | From the start of study treatment through Week 88 | 
| Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as Treatment-emergent Adverse Events | Vital signs parameters included heart rate, blood pressure, temperature, weight, pulse oximetry and respiratory rate. Treatment-emergent were events between administration of investigational product and Week 88 that were absent before treatment or that worsened relative to pre-treatment state. | From the start of study treatment through Week 88 | 
| Number of Participants With Electrocardiogram Abnormalities Reported as Treatment-emergent Adverse Events | AEs observed in participants with clinically significant ECG abnormalities were assessed. Tricuspid valve incompetence was the only abnormality reported as TEAE. ECG parameters included heart rate, PR, QRS, QT, and QTc intervals. Treatment-emergent were events between administration of investigational product and Week 88 that were absent before treatment or that worsened relative to pre-treatment state. | From the start of study treatment through Week 88 | 
| Percentage of Participants With Disease Progression | Progression-free Survival (PFS) was used to evaluate disease progression and the percentage of participants with disease progression. A participant was classified as having disease progression if at least one of the following criteria were met:• Adjudicated respiratory-related mortality. •Adjudicated hospitalization due to IPF exacerbation. •Confirmed decline in percent-predicted FVC of greater than or equal to (>=) 10%. •Confirmed decline in 6 minute walk test (6MWT) >= 50 meters. | Week 52 and 72 | 
| Change From Baseline in Haemoglobin (Hb) Corrected Percent-predicted Diffusion Capacity for Carbon Monoxide (DLco) Through Week 72 | The single breath technique was used to determine the DLco. The test was performed by qualified pulmonary function technicians with experience performing this study. Acceptable test criteria included:• An inspiratory volume of more than 85% of vital capacity. • A stable breath hold of 10 seconds (+/- 2 seconds) with no leaks, Valsalva or Mueller maneuvers. • Expiration in less than 4 seconds with appropriate clearance of dead space. The average of the two best acceptable maneuvers was used. There must be a minimum of 4 minutes between the performances of each test. | Baseline, Week 52 and 72 | 
| Change From Baseline in 6 Minute Walk Test (6MWT) Distance Through Week 72 | The 6MWT measures the distance that a participant can walk on a measured, flat hard surface in a period of 6 minutes. The 6MWT evaluates the global and integrated responses of all body systems involved during walking. | Baseline, Week 52 and 72 | 
| Change From Baseline in Oxygen Saturation by Pulse Oximetry at Week 68 | Participants transcutaneous oxygen saturation were observed by pulse oximetry. | Baseline and Week 68 | 
| Change From Baseline in Lung Volumes Through Week 72 | Lung volumes were evaluated by total lung capacity (TLC), residual volume (RV), and vital capacity (VC). Lung volumes were determined by body plethysmography. | Baseline, Week 52 and 72 | 
| Percentage of Participants With Idiopathic Pulmonary Fibrosis (IPF) Exacerbations | The IPF exacerbations is defined as an acute, clinically significant, deterioration of unidentifiable cause in a participant with underlying IPF. Exacerbations of IPF were adjudicated according to the protocol definition by an independent committee as follows: 1. Confirmed acute IPF exacerbation, 2. Suspected acute IPF exacerbation, 3. Not an IPF exacerbation with an alternative diagnosis provided if possible, and 4. Undetermined due to insufficient information. | Week 52 and 72 | 
| Percentage of Participants With Adjudicated Mortality | Participants all cause mortality were observed. Events that resulted in participant death were adjudicated into respiratory-related mortality or all other cause mortality by an independent committee. | Week 52 and 72 | 
| Percentage of Participants With Adjudicated Hospitalization | Participants who were hospitalized due to IPF exacerbation were observed. All events that resulted in the hospitalization of participants were adjudicated by an independent committee to determine if the event was due to an IPF exacerbation as follows: 1. Exacerbation or progression of IPF, 2. Result of a complication of IPF, 3. Not related to IPF (alternative diagnosis provided), and 4. Undetermined due to insufficient information. | Week 52 and 72 | 
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Through Week 72 | FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. | Baseline, Week 52 and 72 | 
| Change From Baseline in Percent-predicted FEV1 Through Week 72 | FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FEV1 = (observed value)/(predicted value) * 100%. | Baseline, Week 52 and 72 | 
| Change From Baseline in Absolute Forced Vital Capacity (FVC) Through Week 72 | Forced vital capacity (FVC) is a standard pulmonary function test used to monitor disease progression in IPF. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in litres. | Baseline, Week 52 and 72 | 
| Number of Participants With Clinical Global Impression of Severity Scores | The CGI-S is a single, clinician completed, item designed to capture the clinician's impression of the participants IPF severity. Clinicians were asked to consider their experience in this participant population and rate the overall IPF severity of the participant using a 5-point scale (1 = very mild, 5 = very severe). | Week 72 | 
| Number of Participants With Clinical Global Impression of Change Scores | The CGI-C is a single, clinician completed, item designed to capture the clinicians overall impression of change in IPF severity from the baseline state at Screening. Clinicians were asked to rate the participants IPF severity relative to their state at baseline using a 7-point scale (-3 = very much worse, 0 = no change, about the same, 3 = very much improved). | Week 72 | 
| Change From Baseline in University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) Total Score at Week 72 | The UCSD SOBQ is a 24-item questionnaire designed to capture patient-reported shortness of breath. Respondents were asked to rate their breathlessness during 21 activities of daily living using a 6-point scale (0 = not at all breathless, 5 = maximally breathless or too breathless to do this activity). In addition to the 21 activity items, the UCSD SOBQ includes 3 additional questions about limitations due to shortness of breath, fear of harm from overexertion, and fear of shortness of breath. The UCSD SOBQ was scored by summing responses across all 24 items to form a total score. Scores range from 0-120 with higher scores indicative of greater shortness of breath. | Baseline and Week 72 | 
| Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 72 | The SGRQ is a 50-item Patient-reported outcome (PRO) instrument developed to measure respiratory-related health status via 76 weighted responses. The SGRQ is divided into two parts. Part 1 asks respondents to consider the last 3 months and report on their respiratory symptoms using 5-point Likert scales. Part 2 asks respondents to consider their current state and respond to a series of dichotomous yes/no items related to their activities (activities that cause or were limited by breathlessness) and impacts (social functioning, psychological disturbances resulting from airways disease). Total scores and domain scores (symptoms, activities, and impact on daily life) were scored from 0-100, where lower scores indicate better health status. | Baseline and Week 72 | 
| Change From Baseline in Exacerbations of Chronic Pulmonary Disease (EXACT IPF) Total Score Through Week 72 | The EXACT-IPF is a 14-item daily dairy used to capture the IPF related symptoms completed by the participants using an eDiary. The EXACT-IPF total score is the sum of all items ranged from 1 to 14. EXACT-IPF is an interval-level scale ranging from 0 to 100, where the higher scores indicate more severe condition. The EXACT-IPF used Likert scales (with 3 to 6 response options each) to capture participant reported IPF-related symptoms. The scores are the simple sum of item responses for each domain or single item. | Baseline, Week 52 and 72 | 
| Change From Baseline in European Quality of Life-5-Dimension 3 Level Version (EQ-5D-3L) (Including Visual Analog Scale [VAS]) at Week 72 | The EQ-5D-3L is a standardized PRO used to capture respondent's general health status. The questionnaire assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 response options (no problem, some or moderate problems, and unable or extreme problems) that reflect increasing levels of difficulty. The questionnaire also includes a visual analog scale, where the participants were asked to rate their current health on a scale of 0-100, with 0 being the worst imaginable health state. | Baseline and Week 72 | 
| Number of Participants With Patient Global Impression of Severity (PGI-S) for Idiopathic Pulmonary Fibrosis (IPF) | The PGI-S is a single-item, global assessment of participant-perceived IPF severity. The assessment was designed to capture participant perceived IPF-related health status. Participants rate their IPF severity using a 5-point scale (1 = very mild, 5 = very severe). | Week 72 | 
| Number of Participants With Patient Global Impression of Change (PGI-C) for Idiopathic Pulmonary Fibrosis (IPF) | The PGI-C is a single-item, global assessment designed to capture participant-perceived change in their IPF health condition using a 7-point scale (-3 = very much improved, 0 = no change, about the same, 3 = very much worse). | Week 72 | 
| Mean Serum Concentration of Tralokinumab | The mean serum concentration of Tralokinumab were observed. | Predose, 0 hour, and 2 hour postdose on Week 0; predose on Week 4, 48, 72, 82 and 88 | 
| Percentage of Participants Positive for Anti-Drug Antibodies to Tralokinumab | A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study. | From the start of study treatment through Week 88 |