A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Monoclonal Antibody (mAb) in Patients With IPF
- Conditions
- Idiopathic Pulmonary Fibrosis
- Interventions
- Biological: CHF10067 starting doseDrug: PlaceboBiological: CHF10067 intermediate doseBiological: CHF10067 high dose
- Registration Number
- NCT05513950
- Lead Sponsor
- Chiesi Farmaceutici S.p.A.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Test Treatment CHF10067 starting dose A single intravenous (IV) dose of CHF10067 Test Treatment CHF10067 intermediate dose A single intravenous (IV) dose of CHF10067 Test Treatment CHF10067 high dose A single intravenous (IV) dose of CHF10067 Reference treatment Placebo A single dose of placebo (commercial source of 0.9% sodium chloride aqueous solution)
- Primary Outcome Measures
Name Time Method Adverse Event recording From pre-dose up to day 84 Adverse Event recording
- Secondary Outcome Measures
Name Time Method Area under the concentration-time curve from zero to infinity (AUC0-∞) of CHF10067 From pre-dose up to day 84 To evaluate the area under the concentration-time curve from zero to infinity (AUC0-∞) of CHF10067 after a single dose
Time to Cmax From pre-dose up to day 84 To evaluate the Time to Cmax (tmax) (time to maximum observed concentration)
Systemic exposure (area under the concentration-time curve from zero to time) to CHF10067. From pre-dose up to day 84 To evaluate the area under the concentration-time curve from zero to the last quantifiable concentration (AUC0-t) of CHF10067 after a single dose.
12-lead ECG (Electrocardiogram) QTCF From pre-dose up to day 84 the number and percentage of subjects with abnormal actual QTCF (QT corrected for heart rate by Fridericia's formula)
Spirometry FEV1 From pre-dose up to day 84 FEV1 (forced expiratory volume in the first second) parameters will be summarised using descriptive statistics at each analysis time point by treatment.
Pulse rate 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 Pulse rate will be monitored
Maximum plasma concentration (Cmax) of CHF10067 From pre-dose up to day 84 To evaluate the Cmax (maximum observed concentration) after a single dose of CHF10067
Vital signs From pre-dose up to day 84 Systolic and diastolic blood pressure
Diffusing capacity (DLCO) From pre-dose up to day 84 Diffusing capacity (DLCO) parameters will be summarised using descriptive statistics at each analysis time point by treatment.
Body temperature 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 Body temperature will be monitored
Respiratory rate 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 Respiratory rate will be monitored
terminal half-life (t1/2) of CHF10067 From pre-dose up to day 84 To evaluate the Time to t1/2 of CHF10067
Evaluation of CHF10067 immunogenicity profile From predose up to 84 days post dose Evaluation of Anti Drug Antibodies and neutralising antibody (nAb)
12-lead ECG (Electrocardiogram) - QRS interval From pre-dose up to day 84 QRS Interval will be summarised using descriptive statistics at each analysis time point by treatment.
12-lead ECG (Electrocardiogram) - HR From pre-dose up to day 84 The Heart Rate will be summarised using descriptive statistics at each analysis time point by treatment.
Spirometry FVC From pre-dose up to day 84 FVC (forced vital capacity) parameters will be summarised using descriptive statistics at each analysis time point by treatment.
Oxygen saturation From pre-dose up to day 84 Oxygen saturation measured via pulse oximetry
12-lead ECG (Electrocardiogram)-PR interval From pre-dose up to day 84 PR interval will be summarised using descriptive statistics at each analysis time point by treatment.
Trial Locations
- 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
University Hospital Southampton - Department of Respiratory Medicine
🇬🇧Southampton, United Kingdom
Medicines Evaluation Unit - The Langley Building
🇬🇧Manchester, United Kingdom
Liverpool Clinical Research Facility - Liverpool University Hospital Foundation Trust
🇬🇧Liverpool, United Kingdom