This study was an exploratory, two-part, 12-week, Phase 2a study evaluated the mechanism of action of Itepekimab (anti-IL-33-mAb) and its impact on airway inflammation in former and current smokers with COPD, aged 40 to 70 years. This study consisted of participants who had been on a standard-of-care (SoC) mono (long-acting β2-agonist \[LABA\]) or long-acting muscarinic antagonist \[LAMA\]), double (inhaled corticosteroid \[ICS\] + LABA, LABA + LAMA or ICS + LAMA), or triple (ICS + LABA + LAMA) controller therapy for COPD for at least 3 months prior to Screening (Visit 1) with stable dose and regimen for controller therapy for ≥1 month prior to Screening (Visit 1) and during the screening period. Participants would stay on their established controller medications for COPD throughout the duration of the study, with the exception of systemic corticosteroids and/or antibiotics used for acute exacerbation of COPD (AECOPD). Part A would consist of participants who were former smokers with COPD; Part B would consist of participants who were current smokers with COPD. The total study duration for each part (Part A and Part B) was approximately 36 weeks: * 4-week screening period * 12-week treatment period * 20-week followup period
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: subcutaneous
UCLA Medical Center - Harbor- Site Number : 8400006
Torrance, California, United States
National Jewish Health Medical Center- Site Number : 8400012
Denver, Colorado, United States
University of Miami UHealth Tower- Site Number : 8400015
Miami, Florida, United States
University of Kansas Medical Center- Site Number : 8400004
Kansas City, Missouri, United States
Allergy, Asthma and Clinical Research- Site Number : 8400010
Oklahoma City, Oklahoma, United States
Clinical Research Associates of Central PA - Dubois- Site Number : 8400011
DuBois, Pennsylvania, United States
University of Texas - Southwestern Medical Center- Site Number : 8400014
Dallas, Texas, United States
Investigational Site Number : 0560001
Edegem, Belgium
Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760003
Porto Alegre, Rio Grande do Sul, Brazil
Hospital e Maternidade Celso Pierro - PUC-Campinas- Site Number : 0760004
Campinas, São Paulo, Brazil
...and 13 more locations
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Endobronchial Biopsies in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Time frame: Baseline (Week 0) and Week 12
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Bronchial Brushings in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Time frame: Baseline (Week 0) and Week 12
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Nasal Brushings in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Time frame: Baseline (Week 0) and Week 12
Change From Baseline in Interleukin-33 (IL-33) Treated Eosinophil-associated Normalized Enrichment Score in Endobronchial Biopsies at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). IL-33 treated eosinophil-associated gene signature is used to evaluate NES of endobronchial biopsies of former and current smokers, at baseline and Week 12. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Time frame: Baseline (Week 0) and Week 12
Change From Baseline in Interleukin-33 Treated Mast Cell-associated Normalized Enrichment Score in Endobronchial Biopsies at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). IL-33 treated mast cell-associated gene signature is used to evaluate NES of endobronchial biopsies of former and current smokers, at baseline and Week 12. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Time frame: Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Blood Eosinophil Count
Blood samples were collected at specified timepoints to assess change in blood eosinophil count. Baseline was defined as the last available value before first dose of study treatment.
Time frame: Baseline (Week 0) and Week 12
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Event of Special Interests (TEAESIs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Permanent Treatment Discontinuation
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An AE was defined as any untoward medical occurrence in participant or clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. An AE of special interest (AESI) was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor was required. SAEs were defined as any AE that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs were defined as AEs that developed, worsened or became serious during TE period (from first study treatment administration up to end of study).
Time frame: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology During the Treatment-emergent Period
Blood samples were collected to determine the PCSA in hematology during the TE period (from the first treatment administration up to the end of study). Here, Hb = hemoglobin; g/L = grams per liter; M = male; F = female; v/v= volume by volume; LC = leukocyte count; NB = non-black; B = black; ULN = upper limit of normal and EO = eosinophils. Only parameters in which any participant had abnormality are reported.
Time frame: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry During the Treatment-emergent Period
Blood samples were collected to determine the PCSA in chemistry during the TE period (first treatment administration up to the end of study). Here, mmol/L = millimoles/liter; LLN = lower limit of normal; mg/L = milligrams/liter and mcmol/L = micromoles/liter. Only parameters in which any participant had abnormality are reported.
Time frame: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Urinalysis During the Treatment-emergent Period
Urine samples were collected to determine the PCSA in urine during the TE period (from the first treatment administration up to the end of study).
Time frame: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs During the Treatment-emergent Period
Participants were examined to determine the PCSA in vital signs during the TE period (from the first treatment administration up to the end of study). Here, SSBP = sitting systolic blood pressure; mmHg = millimeters of mercury; DFB = decrease from baseline and IFB = increase from baseline. Only parameters in which any participant had abnormality are reported.
Time frame: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) During the Treatment-emergent Period
Single 12-lead ECGs were obtained to determine PCSA during the TE period (from the first treatment administration up to the end of study). Here, QTcB= QT interval corrected by Bazett's formula and QTcF= QT interval corrected by Fridericia formula. Only parameters in which any participant had abnormality are reported.
Time frame: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) to Itepekimab
Blood samples were collected to evaluate antibodies to itepekimab in serum. Treatment-emergent ADA response was defined as a positive response in the ADA assay post first dose when baseline results were negative or missing.
Time frame: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Serum Concentrations of Functional Itepekimab
Blood samples were collected at specified timepoints to obtain serum concentrations of itepekimab.
Time frame: Pre-dose at Weeks 0, 4, 12 and 32