Zephyrus I: Evaluation of Efficacy and Safety 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

NCT03955146

FGCL-3019-091

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 IPF.

Full description

This is a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of pamrevlumab 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.

The study consists of the following study periods:

• Main (double blind, placebo-controlled) phase:

  • Screening period: Up to 6 weeks
  • Treatment period: 48 weeks

• Optional, open-label extension (OLE) phase of pamrevlumab:

  o Access to pamrevlumab will be available until the last participant completes 48 weeks of treatment in the OLE phase, or pamrevlumab is commercially available for the indication of IPF, or the Sponsor decides to end the OLE phase, whichever occurs first.

• Follow-up period/final safety assessments:

  • 28 days after last dose
  • 60 days after last dose: follow-up phone call, for a final safety assessment

During the treatment period, co-administration of an approved IPF therapy (that is, pirfenidone or nintedanib) is acceptable if clinically indicated in the Investigator's opinion, provided that the Investigator assesses the potential risks/benefits of combining approved IPF therapies with blinded study treatment.

Participants who discontinue study treatment for any reason should be encouraged to remain in the study and be followed for all study visits and assessments.

Participants who complete the Week 48 visit of the main study (regardless of the number of study drug infusions received) will be eligible to participate in the optional OLE phase of the study that offers continuing access to pamrevlumab regardless of randomization assignment in the main study.

Enrollment: 393 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 (ATS)/European Respiratory Society (ERS)/Japan Radiological Society (JRS)/Latin American Thoracic Association (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 and corrected by hemoglobin (Hb) value ≥25% and ≤90% at screening (determined locally).
5. Not currently receiving treatment for IPF with an approved therapy (that is, 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.
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. History of other types of respiratory diseases including diseases or disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
8. Medical conditions (for example, myocardial infarction [MI]/stroke within the past 6 month), or logistical challenges that in the opinion of the Investigator preclude the participant's adequate participation in the study.
9. Acute IPF exacerbation during screening or randomization.
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 (that is, 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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393 participants in 6 patient groups, including a placebo group

Main Study Cohort: Pamrevlumab

Experimental group

Description:

Participants will receive pamrevlumab 30 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 3 weeks for up to 48 weeks in the DB period.

Treatment:

Drug: Pamrevlumab

Main Study Cohort: Placebo

Placebo Comparator group

Description:

Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks in the DB period.

Treatment:

Drug: Placebo

Japan Extension Cohort: Pamrevlumab

Experimental group

Description:

Participants will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks.

Treatment:

Drug: Pamrevlumab

Japan Extension Cohort: Placebo

Placebo Comparator group

Description:

Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks.

Treatment:

Drug: Placebo

OLE Period: Pamrevlumab/Pamrevlumab

Experimental group

Description:

Participants who receive pamrevlumab in the DB period will continue to receive the same dose of pamrevlumab for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first.

Treatment:

Drug: Pamrevlumab

OLE Period: Placebo/Pamrevlumab

Experimental group

Description:

Participants who receive placebo matching to pamrevlumab in the DB period, will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first.

Treatment:

Drug: Pamrevlumab