GB28547 Lebrikizumab in IPF

Overview

Status: Not yet recruiting
Keywords: IPF , Idiopathic Pulmonary Fibrosis , Pulmonary Disease
IRB Number: 00066033
Specialty: Pulmonary, Pulmonary
Sub Specialties: Pulmonary Fibrosis, Pulmonary

Brief Summary

  

The primary efficacy objective for this study is as follows:

• To evaluate lebrikizumab compared with placebo as monotherapy or as combination therapy with pirfenidone background compared with placebo in patients with idiopathic pulmonary fibrosis (IPF), as measured by the absolute change from baseline to week 52 in percent predicted FVC. 

The secondary efficacy objectives are to evaluate lebrikizumab compared with placebo as monotherapy or as combination therapy with pirfenidone background therapy compared with placebo in patients with IPF as measure by: 

• The efficacy of lebrikizumab compared with placebo in patients with IPF on the basis of pulmonary function, diffusion capacity, death, non-elective hospitalization from any cause, and acute IPF exacerbations

• The distance walked in 6 minutes and health-related quality of life questionnaires

The safety objectives for this study are as follows:

• To evaluate the safety of lebrikizumab as monotherapy compared with placebo in patietns with IPF

-To evaluate the safety of lebrikizumab with pirfenidone as background therapy compared with placebo with pirfenidone as background therapy in patients with IPF

The pharmacodynamic (PD) objectives for this study are as follows:

• To characterize the pharmacokinetics of lebrikizumab in patients with IPF

The exploratory objectives for this study are as follows:

• To evaluate the efficacy of lebrikizumab compared with placebo as monotherapy compared with placebo or as coombination therapy with pirfenidone compared with placebo in patients with IPF on the basis of changes in: use of supplemental oxygen therapy, the number of respiratory hospitalizations, DLco, and quantitative lung fibrosis (QLF) score on high resolution computed tomography (HRCT).

• To evaluate potential prognostic and predictive serum and whole blood RNA and DNA biomarkers associated with IPF

 

 

 

Principal Investigator: Mary Scholand
Department: Pulmonary
Co Investigator:

Contact Information

Name:Patrick Carey
Phone: 801-581-5864
Email: patrick.carey@hsc.utah.edu

Inclusion Criteria

Patients must meet the following criteria for study entry: 
• Able and willing to provide written informed consent and to comply with the study protocol 
 
• Age ≥40 years at Visit 1 
 
• Have a diagnosis of IPF based on the 2011 ATS/ERS/JRS/ALAT consensus statement on IPF within the previous 4 years from time of screening and confirmed at baseline. 
 
• Have a central review assessment of an HRCT performed during the screening period or within 12 months prior to the start of screening. 
 
• All patients who have undergone a SLB as part of their initial workup should have pathology slides sent in for SLB central review assessment.
 
A Multidisciplinary Discussion of Diagnosis (MDD) based on 2011 ATS/ERS/JRS/ALAT guidelines will be utilized to finalize the diagnosis in the event the initial central review outcome results for HRCT and SLB are disparate (inconsistent with UIP/definite UIP
 
• Eligibility will be determined based on Table 1: 
Table 1 Combined High Resolution Computed Tomography and Surgical Lung Biopsy Eligibility Assessment 
    SLB Assessment SLB Assessment SLB Assessment SLB Assessment SLB Assessment SLB Assessment
    Definite UIP Probable UIP Possible UIP Non-Classifiable fibrosis Inconsistent with UIP No SLB
HRCT Assessment Definite UIP Eligible Eligible Eligible Eligible Not Eligible Eligible
HRCT Assessment Possible UIP Eligible Eligible Not Eligible Not Eligible Not Eligible Not Eligible
HRCT Assessment Inconsistent with UIP Not Eligible Not Eligible Not Eligible Not Eligible Not Eligible Not Eligible

HRCT = high resolution computed tomography; SLB= surgical lung biopsy; UIP= usual interstitial pneumonitis 

 
Additionally, patients must meet the following criteria for study entry: 
• FVC ≥40% and ≤100% of predicted at screening 
 
• Stable baseline lung function as evidenced by a difference of <10% in FVC (L) measurements between screening and Day 1/Visit 2 prior to randomization 
 
• DLCO ≥25% and ≤90% of predicted at screening 
 
• Ability to walk ≥100 meters unassisted in 6 minutes
• Cohort A: No background IPF therapy for ≥ 4 weeks allowed prior to randomization and
throughout the placebo-controlled study period
• Cohort B: Stable dose of pirfenidone ≤ 2403 mg/d for ≥ 4 weeks required prior to
randomization and throughout the placebo-controlled study period

 

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from study entry: 
 
• History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known 
hypersensitivity to any component of the lebrikizumab injection 
 
• Evidence of other known causes of interstitial lung disease (ILD) (e.g., domestic and occupational environmental exposures, connective tissue disease, and drug toxicity)  
 
• Lung transplant expected within 12 months of screening 
 
• Evidence of clinically significant lung disease other than IPF (e.g., asthma or chronic obstructive pulmonary disease [COPD]) 
 
• Post bronchodilator forced expiratory volume in 1 second (FEV1)/FVC ratio <0.7 at screening 
 
• Positive bronchodilator response evidenced by an increase of ≥12% predicted and 200 mL increase in either FEV1 or FVC 
 
• Any clinically significant medical disease (other than IPF) that is associated with an expected survival of <12 months, likely to require a change in therapy during the study, or likely to impact the ability of the patient to participate in the study in the opinion of the investigator, or impact the study efficacy or safety assessments 
 
• Requirement for continuous medical care and assistance, or limited ability to self care that would impact the ability of patient to participate in the study or to perform the study-related assessments 
 
• Class IV New York Heart Association chronic heart failure or historical evidence of left ventricular ejection fraction <35% 
 
• Hospitalization due to an exacerbation of IPF within four weeks prior to, or during screening 
 
• Known current malignancy or current evaluation for a potential malignancy
• Major episode of infection requiring any of the following:
Admission to the hospital for ≥ 24 hours within 4 weeks prior to screening or
during screening and run-in period
Treatment with antibiotics (IV, IM, oral, or inhaled) within 4 weeks
prior to screening or during screening period
• Active or recent (≤ 4 weeks prior to Day 1/Visit 2) upper or lower respiratory tract
infection
• Listeria monocytogenes infection or active parasitic infection within 6 months
prior to Day 1/Visit 2
• Active tuberculosis requiring treatment within 12 months prior to screening
• Known immunodeficiency, including but not limited to HIV infection
• Past use of any anti–IL-13 or anti–IL-4/IL-13 therapy, including lebrikizumab
Patients participating in a clinical trial that has not been unblinded should be
assumed to have received the active drug
• Evidence of acute or chronic hepatitis or known liver cirrhosis
• AST, ALT, or total bilirubin elevation ≥ 2.0 × the upper limit of normal
during screening
• Clinically significant abnormality on ECG at screening or laboratory tests
(hematology, serum chemistry, and urinalysis) that, in the opinion of the investigator,
may pose an additional risk in administering study drug to the patient
• Receipt of a live/attenuated vaccine within the 4 weeks prior to Visit 1
• Chronic treatment with any of the following within 4 weeks or five half-lives
(whichever is longer) prior to randomization visit (Day 1/Visit 2):
Immunosuppressive or immunomodulatory therapies (e.g., azathioprine,
cyclosporine A, cyclophosphamide, D-penicillamine, interferon-gamma, tumor
necrosis factor-α antagonists)
Cytotoxic drugs (e.g., colchicine) if used for IPF indication
Pirfenidone (Exclusion limited to Cohort A)
N-acetylcysteine
Pulmonary hypertension therapies (e.g., endothelin receptor antagonist,
phosphodiesterase type-5 inhibitor, riociguat, prostacyclin or prostacyclin
analogue)
Tyrosine kinase inhibitors including exclusion of nintedanib for Cohort A and Cohort B
Warfarin or other anticoagulant therapy if given for IPF indication
Any unlicensed therapy given for the indication of IPF
Any investigational agent
• Chronic oral corticosteroid therapy is not permitted within 4 weeks prior to screening
(Visit 1) or during screening and run-in period
• History of alcohol, drug, or chemical abuse that would impair or risk the patient’s full
participation in the study, in the opinion of the investigator
• Female patients of reproductive potential who are not willing to use a highly effective
method of contraception (e.g., contraceptive pill or transdermal patch, spermicide
and barrier [i.e., condoms], intrauterine device, implants for contraception, injections
for contraception [with prolonged release], hormonal vaginal device, sterilization,
surgical tubal ligation) for the duration of the study and for at least 18 weeks after
the last dose of lebrikizumab or placebo study treatment) (see Appendix 7)
• Pregnant or lactating
• Body weight < 40 kg

 

Exclusions Limited to Cohort B (Pirfenidone Background)
• Known achalasia, esophageal stricture, or esophageal dysfunction sufficient to limit the
ability to swallow oral medication
• Tobacco smoking within 3 months of screening or unwillingness to avoid smoking
throughout the study (eg, cigarette, pipe, cigar)
• Any condition that, as assessed by the investigator, might be significantly exacerbated by the
known side effects associated with pirfenidone
• Known or suspected peptic ulcer
• Any of the following abnormal laboratory tests:
o Total bilirubin above the upper limit of the normal range (ULN), except in
patients with predominantly unconjugated hyperbilirubinemia (eg, Gilbert’s
syndrome)
o Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 × ULN
o Alkaline phosphatase > 2 × ULN
o Creatinine clearance < 40 mL/min, calculated using the Cockcroft-Gault formula
• Ongoing use or following therapies within 4 weeks of randomization (Day 1/Visit 2):or
during the study
o Strong inhibitors of CYP1A2 (eg, fluvoxamine or enoxacin)
o Moderate inducers of CYP1A2 (eg, tobacco smoking)