A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Monoclonal Antibody (mAb) in Patients With IPF

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of CHF10067 (the study drug) and any side effects that might be associated with it. In addition, the study will evaluate how much of the study drug gets into the bloodstream and how long the body takes to remove it. The body's immune response to the study drug will also be evaluated. The study may also evaluate the effect of the study drug on the level of a certain protein in the body. Chiesi is conducting this study on people affected by idiopathic pulmonary fibrosis (IPF, a lung disease). The reason Chiesi is doing this study is to establish the doses suitable for future studies in subjects

Official Title
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A Phase Ib, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of an Intravenous Monoclonal Antibody (mAB) After Single Ascending Doses in Subjects Affected by Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Biological: CHF10067 starting dose
* Biological: CHF10067 intermediate dose
* Biological: CHF10067 high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's written informed consent obtained prior to any study-related procedure. Males or females, of any race, aged between 40 and 80 years of age, inclusive. Body weight ≥ 45 kg. Diagnosis of IPF as defined by current American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines. Diagnosis of IPF must be within the past 5 years prior to enrolment, and in the opinion of the Investigator, has been stable for at least 3 months. Subjects not receiving any IPF treatment (including subjects with previous use of antifibrotic treatment that has been stopped) or receiving well-tolerated standard of care approved treatments at a stable dose for at least 8 weeks prior to screening (nintedanib or pirfenidone) and it is anticipated the dose will remain unchanged throughout the study. Forced vital capacity (FVC) ≥ 50% of predicted and ratio of forced expiratory volume in the first second (FEV1)/FVC ≥ 0.7 at screening and prior to randomization. Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) from 35% to 79% of predicted, inclusive at screening and prior to randomization. Able to understand the study procedures and the risks involved. Male and Female subjects following contraceptive requirements detailed in the study protocol. Exclusion Criteria: History of respiratory tract infection within 2 months prior to screening and up to Day 1 of the study. History of acute exacerbation of IPF within 3 months prior to screening and up to Day 1 of the study Active diagnosis of lung cancer or a history of lung cancer. Active cancer or a history of cancer (other than lung cancer) with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Infiltrative lung disease other than IPF Subjects exhibiting unhealed wounds or foot ulcers or have known history of wound healing complications. Chronic heart failure categorized as New York Heart Association Class II, III, or IV; clinical diagnosis of cor pulmonale requiring specific treatment; or severe pulmonary hypertension Currently receiving, or have received, a systemic corticosteroid, immunosuppressant, cytotoxic therapy, vasodilator therapy for pulmonary hypertension, or unapproved or investigational treatment for IPF within 4 weeks prior to screening or prior to randomization. Coronavirus disease-2019 (COVID-19) vaccine at least 7 days before dosing. Any systemic symptoms (e.g. myalgia, fever, chills, fatigue, etc.) after COVID-19 vaccine should subside at least 2 days before the Day 1 visit. Documented COVID-19 diagnosis within the last 8 weeks or which has not resolved within 14 days prior to screening or before treatment. Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation or any other substance used in the study. History of allergic or anaphylactic reaction to human, humanised, chimeric, immunoglobulins (Igs), or murine monoclonal antibodies. Clinically relevant abnormal laboratory values (clinical chemistry and haematology) at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the study results according to Investigator judgement. . Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Sequential Assignment
Interventional Model Description: Treatment with single dose escalation: 3 different cohorts receive 3 incremental doses of Investigational Medicinal Product. Each cohort can start when the previous cohort is complete and the data are evaluated by the Safety Committee.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Treatment<br>A single intravenous (IV) dose of CHF10067 | Biological: CHF10067 starting dose<br>* Intravenous administration of a starting dose of the monoclonal antibody<br>Biological: CHF10067 intermediate dose<br>* Intravenous administration of an intermediate dose of the monoclonal antibody<br>Biological: CHF10067 high dose<br>* Intravenous administration of a high dose of the monoclonal antibody<br>|
| Placebo Comparator: Reference treatment<br>A single dose of placebo (commercial source of 0.9% sodium chloride aqueous solution) | Drug: Placebo<br>* Intravenous administration of a physiological solution as placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event recording | Adverse Event recording | From pre-dose up to day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of CHF10067 | Calculation of the Area under the curve | From pre-dose up to day 84 | 
| Pharmacokinetic profile of CHF10067 | Cmax (maximum observed concentration) | From pre-dose up to day 84 | 
| Pharmacokinetic profile of CHF10067 | tmax (time to maximum observed concentration) | From pre-dose up to day 84 | 
| Pharmacokinetic profile of CHF10067 | Half life | From pre-dose up to day 84 | 
| Evaluation of the CHF10067 immunogenicity profile | Evaluation of Anti Drug Antibodies and neutralising antibody (nAb) | From predose up to 84 days post dose | 
| Vital signs | Systolic and diastolic blood pressure | From pre-dose up to day 84 | 
| Oxygen saturation | Oxygen saturation measured via pulse oximetry | From pre-dose up to day 84 | 
| 12-lead ECG (Electrocardiogram) | Heart Rate | From pre-dose up to day 84 | 
| 12-lead ECG (Electrocardiogram) | PR (PR interval) | From pre-dose up to day 84 | 
| 12-lead ECG (Electrocardiogram) | QRS Interval | From pre-dose up to day 84 | 
| 12-lead ECG (Electrocardiogram) | QTCF (QT corrected for heart rate by Fridericia's formula) | From pre-dose up to day 84 | 
| Spirometry | FEV1 (forced expiratory volume in the first second) | From pre-dose up to day 84 | 
| Spirometry | FVC (forced vital capacity) | From pre-dose up to day 84 | 
| Diffusing capacity (DLCO) | Diffusing capacity (DLCO) | From pre-dose up to day 84 |