Zephyrus II: Efficacy and Safety Study of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)

FibroGen

Status and phase: Terminated; Phase 3

Conditions: Idiopathic Pulmonary Fibrosis

Treatments: Drug: Pamrevlumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04419558

FGCL-3019-095

Details and patient eligibility

About

This is a Phase 3 trial to evaluate the efficacy and safety of 30 milligrams (mg)/kilogram (kg) intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in participants with Idiopathic Pulmonary Fibrosis (IPF). There is a 48-week randomized treatment phase followed by an optional, open-label extension phase.

Full description

The intent of this study is to evaluate the efficacy and safety of pamrevlumab as monotherapy in participants with IPF. Participants who are not being treated with approved IPF therapies (that is, nintedanib or pirfenidone) may be eligible for screening. Examples of reasons participants may not be treated with approved IPF therapies include but are not limited to:

Intolerant or not responsive to approved IPF therapies Ineligible to receive these therapies Participant voluntarily declines to receive approved IPF therapies after being fully informed of the potential benefits/risks

NOTE: No participant should discontinue an approved IPF therapy for the purpose of enrolling in this study.

During the 48-week treatment phase of the study, co-administration of an approved IPF therapy (such as, pirfenidone or nintedanib) is acceptable if clinically indicated in the Investigator's opinion, after assessment of potential risks/benefits of such combination with blinded study treatment.

Participants who complete the 48-week study will be eligible for an optional, open-label extension phase with continued access to pamrevlumab, regardless of their randomized assignment.

Enrollment: 372 patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) guidelines within the past 7 years prior to study participation.
2. High-resolution computed tomography (HRCT) scan at Screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing.
3. FVCpp value >45% and <95% at Screening and Day 1 (prior to randomization).
4. Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥25% and ≤90%.
5. Not currently receiving treatment for IPF with an approved therapy for IPF (such as, pirfenidone or nintedanib) for any reason, including prior intolerance or lack of response to an approved IPF therapy, or choice to forego treatment with an approved IPF therapy after a full discussion with the Investigator regarding risks/benefits of such therapy.

Key Exclusion Criteria:

1. Previous exposure to pamrevlumab.
2. Evidence of significant obstructive lung disease, as evidenced by spirometry or HRCT.
3. Female participants who are pregnant or nursing.
4. Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study.
5. Interstitial lung disease other than IPF.
6. Sustained improvement in the severity of IPF during the 12 months prior to screening.
7. Other types of respiratory diseases that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study, including diseases of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
8. Certain medical conditions, that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study (such as, myocardial infarction/stroke, severe chronic heart failure, pulmonary hypertension, or cancers).
9. Acute IPF exacerbation during Screening or Randomization including hospitalization due to acute IPF exacerbation within 4 weeks prior to or during screening.
10. Use of any investigational drugs or unapproved therapies, or participation in any clinical trial with an investigational new drug within 30 days prior to screening. Or use of approved IPF therapies (such as, pirfenidone or nintedanib) within 1 week prior to screening.
11. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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372 participants in 2 patient groups

Pamrevlumab

Experimental group

Description:

Treatment phase: Pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks. Open-label extension phase: Pamrevlumab 30 mg/kg administered by intravenous infusion, every 3 weeks for up to 48 weeks

Treatment:

Drug: Pamrevlumab

Placebo

Experimental group

Description:

Pamrevlumab-matching placebo administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks

Treatment:

Drug: Placebo