Clinical trial NCT05513950: A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Monoclonal Antibody (mAb) in Patients With IPF
Official title: PhIb, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, and PK of an i.v. mAb After Single Ascending Doses in Subjects Affected by Idiopathic Pulmonary Fibrosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2022-08-24
Enrollment: 24
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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 patients affected by idiopathic pulmonary fibrosis (IPF, a lung disease).

Chiesi is doing this study to establish the doses suitable for future studies.

Detailed description: The principal aim of this study is to obtain safety and tolerability data when CHF10067 is administered intravenously as single ascending doses to subjects with IPF. This information, together with the pharmacokinetic (PK) and immunogenicity data, will help establish the doses suitable for future studies in subjects. The effect of CHF10067 on TG2 levels will also be 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 will be used so that in each cohort 2 subjects (1 CHF10067 and 1 placebo) will be dosed at least 24 hours before the remaining 6 subjects.

The study will be double-blind and placebo-controlled to avoid bias in the collection and evaluation of data during its conduct. Placebo has been chosen as the comparison treatment to assess whether any observed effects are treatment-related or simply reflect the study conditions.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Event recording
timeFrame: From pre-dose up to day 84
Secondary outcomes:
measure: Systemic exposure (area under the concentration-time curve from zero to time) to CHF10067.
timeFrame: From pre-dose up to day 84
measure: Area under the concentration-time curve from zero to infinity (AUC0-∞) of CHF10067
timeFrame: From pre-dose up to day 84
measure: Maximum plasma concentration (Cmax) of CHF10067
timeFrame: From pre-dose up to day 84
measure: Time to Cmax
timeFrame: From pre-dose up to day 84
measure: terminal half-life (t1/2) of CHF10067
timeFrame: From pre-dose up to day 84
measure: Evaluation of CHF10067 immunogenicity profile
timeFrame: From predose up to 84 days post dose
measure: Vital signs
timeFrame: From pre-dose up to day 84
measure: Oxygen saturation
timeFrame: From pre-dose up to day 84
measure: 12-lead ECG (Electrocardiogram) - HR
timeFrame: From pre-dose up to day 84
measure: 12-lead ECG (Electrocardiogram)-PR interval
timeFrame: From pre-dose up to day 84
measure: 12-lead ECG (Electrocardiogram) - QRS interval
timeFrame: From pre-dose up to day 84
measure: 12-lead ECG (Electrocardiogram) QTCF
timeFrame: From pre-dose up to day 84
measure: Spirometry FEV1
timeFrame: From pre-dose up to day 84
measure: Spirometry FVC
timeFrame: From pre-dose up to day 84
measure: Diffusing capacity (DLCO)
timeFrame: From pre-dose up to day 84
measure: Body temperature
timeFrame: at screening, pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 days post-dose
measure: Pulse rate
timeFrame: At screening, pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 days post-dose
measure: Respiratory rate
timeFrame: At screening, pre-dose, every 15 minutes during the infusion (e.g., 15, 30, 45, 60, 75, 90, 105, etc.), at the end of the infusion and 30 min, 1, 2, 3, 4, 6, 8, and 20 hours after the end of the infusion and 5, 7, 14, 28, 56, and 84 days post-dose
Other outcomes:
measure: Transglutaminase 2 levels in plasma
timeFrame: From predose up to 84 days post dose
Locations:
city: Skopje
country: North Macedonia
facility: PHI University Clinic of Pulmonology and Allergology
city: Kyiv
country: Ukraine
facility: Medical Center of Limited Liability Company "Arensia Exploratory Medicine", department of Clinical Trials
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital - NIHR Birmingham Clinical Research Facility - University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHSFT - Cambridge Biomedical Campus
city: Dundee
country: United Kingdom
facility: University of Dundee, NHS Tayside - Ninewells Hospital & Medical School
city: Edinburgh
country: United Kingdom
facility: Interstitial Lung Disease Research - NHS Lothian - Royal Infirmary of Edinburgh,
city: Liverpool
country: United Kingdom
facility: Liverpool Clinical Research Facility - Liverpool University Hospital Foundation Trust
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit - The Langley Building
city: Southampton
country: United Kingdom
facility: University Hospital Southampton - Department of Respiratory Medicine
Study officials:
affiliation: Liverpool University Hospitals NHS Foundation Trust
name: Lisa Spencer
role: PRINCIPAL_INVESTIGATOR
References: