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

Chiesi Farmaceutici S.p.A.52 enrolled

Overview

Assess the safety of CHF10067 (study drug) and any side effects that might be associated with it. The study also evaluated 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 was evaluated. Chiesi conducted this study in patients affected by idiopathic pulmonary fibrosis (IPF, a progressive and chronic lung disease). Chiesi performed this study to establish the drug doses that would be suitable for future studies (a dose finding study).

The principal aim of this study was to obtain safety and tolerability data when CHF10067 was administered intravenously as single ascending doses to subjects with IPF (a progressive and chronic lung disease). This information, together with the pharmacokinetic (PK) and immunogenicity data is part of a dose finding efforts, for future clinical studies. The effect of CHF10067 on transglutaminase 2 (TG2) levels was also investigated as an exploratory endpoint. A sequential group, single ascending dose design has been chosen for safety reasons because CHF10067 is in the early stages of clinical development and no data in the IPF population has been collected so far. In addition, sentinel dosing was used so that in each cohort 2 subjects (1 CHF10067 and 1 placebo) was administered at least 24 hours, before the remaining 6 subjects. The study was double-blind and placebo-controlled to avoid bias in the collection and evaluation of data during its conduct. Placebo was chosen as the comparison treatment to assess whether any observed effects are treatment-related or reflect the study conditions.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subject's written informed consent obtained prior to any study-related procedure. * Males or females, of any race, aged ≥ 40 years of age. * 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 for at least 2 weeks prior to screening) 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. * Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) ≥ 35% at screening. * 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 lower respiratory tract infection within 4 weeks 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 4 weeks or which has not resolved within 7 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.

Locations (9)

PHI University Clinic of Pulmonology and Allergology

Skopje, North Macedonia

Medical Center of Limited Liability Company "Arensia Exploratory Medicine", department of Clinical Trials

Kyiv, Ukraine

Queen Elizabeth Hospital - NIHR Birmingham Clinical Research Facility - University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

Royal Papworth Hospital NHSFT - Cambridge Biomedical Campus

Cambridge, United Kingdom

University of Dundee, NHS Tayside - Ninewells Hospital & Medical School

Dundee, United Kingdom

Interstitial Lung Disease Research - NHS Lothian - Royal Infirmary of Edinburgh,

Edinburgh, United Kingdom

Liverpool Clinical Research Facility - Liverpool University Hospital Foundation Trust

Liverpool, United Kingdom

Medicines Evaluation Unit - The Langley Building

Manchester, United Kingdom

University Hospital Southampton - Department of Respiratory Medicine

Southampton, United Kingdom

Outcomes

Primary Outcomes

1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs

Evaluate reported adverse events (AEs) and serious adverse events (SAEs). The number of subjects affected by AEs or SAEs is presented below. Please note: comprehensive summaries of AEs and SAEs are presented in section 'Adverse Events'; these include the preferred term of the AE or SAE, the number of subjects affected, and the number of events for a each preferred term.

Time frame: From pre-dose (baseline) up to day 84.

Secondary Outcomes

2_Systemic Exposure [Area Under the Concentration-time Curve From Zero to Time (AUC0-t)]

Evaluate the area under the concentration-time curve (AUC) from zero to the last quantifiable concentration (AUC0-t) of CHF10067 after a single dose.

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.

3_Area Under the Concentration-time Curve (AUC) From Zero to Infinity (AUC0-∞)

Evaluate the area under the concentration-time curve (AUC) from zero to infinity (AUC0-∞) of CHF10067 after a single dose.

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.

4_Pharmacokinetics -- Maximum Plasma Concentration (Cmax)

Evaluate the Cmax (maximum observed concentration) after a single dose of CHF10067.

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.

5_Pharmacokinetics -- Time to Maximum Observed Concentration (Tmax)

Evaluate the time to maximum observed concentration (tmax).

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.

6_Pharmacokinetics -- Serum Concentration at the End of Infusion (Cinf)

Evaluate serum concentration at the end of infusion (Cinf) of CHF10067.

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion).

7_Pharmacokinetics -- Time at the End of Infusion (Tinf)

Evaluate the time of serum concentration at the end of infusion (Tinf). Time at the end of the infusion.

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion).

8_Pharmacokinetics -- Clearance (CL)

Evaluate clearance (CL) of CHF10067.

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.

9_Pharmacokinetics -- Volume of Distribution (Vz)

Evaluate volume of distribution (Vz) CHF10067.

Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.

10_Pharmacokinetics -- Terminal Half-life (t1/2)

Evaluate the terminal half-life (t1/2) of CHF10067.

Time frame: From pre-dose (baseline) up to day 84.

11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline

Forced expiratory volume in the first second (FEV1) parameters, summarised using descriptive statistics at each analysis time point by treatment. Summary results show the change from baseline of the percent predicted.

Time frame: Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose.

12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline

Forced vital capacity (FVC) parameters will be summarised using descriptive statistics at each analysis time point by treatment. Summary results show the change from baseline of the percent predicted.

Time frame: Text adjusted Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose.

13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure

Evaluate abnormal changes in systolic and diastolic blood pressure from baseline at any post-baseline time point.

Time frame: From pre-dose (baseline) up to day 84.

14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb).

Evaluate the immunogenicity profile of CHF 10067 in serum, with respect to the development of anti-drug antibody (ADA) and neutralising antibody (nAb). A robust immunogenicity profile indicates the potential for the drug to trigger an immune response in patients, leading to the formation of ADAs. These antibodies can affect the drug's efficacy, safety, and pharmacokinetics. Detecting the presence of ADAs in serum samples was performed using an enzyme linked immunosorbent assay (ELISA), a validated assay method. Neutralizing Antibody (nAb) are a subset of ADAs that can interfere with the drug's therapeutic activity by blocking its binding to the target or inhibiting its downstream effects. The presence of ADAs and nAbs can affect the drug's pharmacokinetics (PK) by altering its absorption, distribution, metabolism, and excretion. This can lead to changes in drug exposure and potentially impact efficacy and safety.

Time frame: Pre-dose (baseline), at day 14, 28, 56, 84, and in case of early termination.

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

Overview

Conditions

Interventions

Eligibility

Locations (9)

Outcomes

Primary Outcomes

Secondary Outcomes