The purpose of this study is to evaluate efficacy and safety of olokizumab (OKZ) compared to placebo in patients progressive fibrosing Interstitial lung diseases (ILD).
This is a phase 2/3 study with double-blind parallel-group adaptive design. The study will include the following periods: 1. Screening period (4 weeks) Screening period (before the first administration of the test drug). Before being included in the study, patients will be provided with complete information about this clinical trial and signs the Informed consent Form (IF). After that the researcher will decide whether or not the patient can be randomized into the study. 2. Double-blind Treatment period (48 weeks). Following the completion of a Treatment period, all patients will be enrolled in Follow-up Period (FU). 3. Follow-up Period (24 weeks). During the FU Period, patients will visit study sites after 4,12 and 24 weeks after the end of the Treatment Period to complete FU-1 (Week 52), FU-2 (Week 60) and FU-3 (Week 72) visits. The overall study duration for the patients will be approximately 76 weeks (including the 4 weeks screening period) The analysis will be conducted in two sequential steps: * the interim analysis after 61 percent (%) of patients have completed the Treatment period (not including the FU period) * the final analysis when all patients have completed all periods (the Treatment and the FU periods).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
138
Olokizumab is a sterile solution for subcutaneous injection in a 2-mL clear Type I glass vial, containing a target fill volume of 0.5 mL (for withdrawal of no less than 0.4 mL) of olokizumab drug substance at a concentration of 160 milligrams (mg)/mL.
Placebo (sodium chloride 0.9 %) does not contain any active pharmaceutical ingredients. Placebo will be supplied in 2-mL, 5-mL, or 10-mL ampoules made of low-density polyethylene or polypropylene.
The rate of forced vital capacity (FVC)
FVC decline rate assessed over 48 weeks of therapy. FVC is the maximum amount of air that can be exhaled when blowing out as fast as possible.
Time frame: 48 weeks
Change in FVC from baseline
Absolute change in FVC from baseline at treatment weeks 24 and 48.
Time frame: 24, 48 weeks.
Change in FVC.% predicted
Change in FVC% predicted from baseline at treatment weeks 24 and 48.
Time frame: 24,48 weeks
Number of patients (in %) with a decrease in FVC
Number of patients (in %) with a decrease in FVC of ≥10 % predicted.at treatment week 48.
Time frame: 48 weeks
Number of patients (in %) with improved pulmonary function
Number of patients (in %) with improved pulmonary function (change from baseline in FVC \>0% predicted.
Time frame: 48 weeks
Change of Diffusing capacity of the lungs for carbon monoxide (DLCO)
Change in absolute values of DLCO from baseline at treatment weeks 24 and 48.
Time frame: 24,48 weeks
Change in the values of quantitative assessment of lung fibrosis from baseline
Change in the values of quantitative assessment of lung fibrosis from baseline based on high-resolution computed tomography (HRCT) data at treatment week 48.
Time frame: 48 weeks
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Proportion of patients with progression or death
Proportion of patients with progression or death: the first event defined as death. Progression is a decrease in FVC ≥10% predicted, or decrease in DLCO ≥15% predicted from their baseline values.
Time frame: 48 weeks
Time to progression or death assessed over 48 weeks of treatment
Time to progression or death assessed over 48 weeks of treatment.
Time frame: 48 weeks
Time to exacerbation over 48 weeks of treatment
An exacerbation of idiopathic lung fibrosis and other ILDs is defined as worsening shortness of breath over the past 30 days combined with evidence of new bilateral lesions appearing as ground-glass opacities and/or consolidations on a chest HRCT scan without other alternative causes (infections and other).
Time frame: 48 weeks
Proportion of patients with exacerbation at treatment weeks 24 and 48
Proportion of patients with exacerbation over 48 weeks of treatment.
Time frame: 24,48 weeks
Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea scores from baseline at treatment weeks 24 and 48
FACIT-Dyspnea questionnaire includes Dyspnea subscale, that measures the severity of dyspnea when doing everyday activities, and Functional Limitations subscale that measures the amount of difficulty experienced while doing these activities due to dyspnea in the past 7 days. Both subscales contain 10 items scored from 0 (best) to 4 (worst). A raw score (normal-worst range 0-30) is calculated as: Sum individual item scores \* 10 / number of items answered. Raw scores are then converted to scale scores using the table included in the FACIT Dyspnoea Scale Short Form Scoring Guideline. Scale score range: Dyspnea subscale from 27.7 (normal condition) to 75.9 (severe symptoms); Functional Limitations subscale from 29.7 (not limited) to 76.7 (severely limited)
Time frame: 24,48 weeks
Change in Short Form-36 (SF-36) scores from baseline at treatment weeks 24 and 48
36-Item Short-Form Health Survey (SF-36) is a patient reported survey of health consisting of 36 items that taps eight health concepts (domains): vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. It also includes a single item that provides an indication of perceived change in health. For each domain a scaled score is calculated as the weighted sum of the questions in this section. Each scale is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time frame: 24,48 weeks
Change in Modified Medical Research Council ( mMRC) dyspnea score from baseline at treatment weeks 24 and 48
Modified Medical Research Council (mMRC) Dyspnea Scale is used to assess perceived degree of baseline functional disability due to dyspnea. Participants indicate a score on 5-point scale according to the severity of their symptoms: none = 0; mild = 1; moderate = 2; severe =3; very severe = 4
Time frame: 24,48 weeks