A Study to Evaluate the Efficacy and Safety of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis

Phase 3

Terminated

Conditions: Idiopathic Pulmonary Fibrosis

Interventions: Drug: PRM-151 (Zinpentraxin Alfa)
Drug: Placebo

Registration Number: NCT04552899

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This phase III study will evaluate the efficacy, safety and pharmacokinetics (PK) of recombinant human pentraxin-2 (rhPTX-2; PRM-151) zinpentraxin alfa, compared with placebo in participants with idiopathic pulmonary fibrosis (IPF).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 665

Inclusion Criteria

Documented diagnosis of IPF per the 2018 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) Clinical Practice Guideline
High-resolution computed tomography (HRCT) pattern consistent with the diagnosis of IPF, confirmed by central review of Chest HRCT and central review of any available lung biopsy (LB)
Minimum 6 minute walk distance (6MWD) of 150 meters with maximum use of 6 L/min at sea-level and up-to 8 L/min at altitude of supplemental oxygen while maintaining oxygen saturation of greater than or equal to (>/= )83% during the 6 minute walk test (6MWT) during screening
FVC >/= 45% predicted during screening as determined by the over-reader
Forced expiratory volume in 1 second (FEV1)/FVC ratio greater than (>) 0.70 during screening determined by the over-reader
Diffusing capacity for carbon monoxide (DLCO) >/= 30% and less than or equal to (</=) 90% of predicted at screening as determined by the over-reader
If receiving pirfenidone or nintedanib treatment for IPF, the participant must have been on treatment for at least 3 months and a stable dose for at least 4 weeks prior to screening, and during screening
If not currently receiving nintedanib or pirfenidone treatment (either treatment naïve or having previously taken and discontinued) must have discontinued such treatment >/= 4 weeks prior to screening and during screening
Anticipated life expectancy of at least 12 months at baseline
Participant and investigator considered all medicinal treatment options and/or possibly lung transplantation prior to considering participation in the study.
For women of childbearing potential (excluding participant enrolling in Japan): agreement to remain abstinent or use contraception
For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm
Anticipated life expectancy of at least 12 months at baseline, according to the investigator's judgment
For participant enrolled in the extended China enrollment phase: current resident of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry

Exclusion Criteria

Evidence of other known causes of Interstitial Lung Disease (ILD)
FVC% predicted value showing repeated increase in the 6 months period prior to screening and including screening value
Emphysema present on greater than or equal to (>/=) 50% of the HRCT, or the extent of emphysema is greater than the extent of fibrosis, according to central review of the HRCT
Receiving nintedanib in combination with pirfenidone
Received cytotoxic, immunosuppressive, cytokine modulating, or receptor antagonist agents (including but not limited to methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine or other steroid sparing agent) within 4 weeks prior to or during screening
Receiving systemic corticosteroids equivalent to prednisone > 10 mg/day or equivalent within 2 weeks prior to or during screening
Acute respiratory or systemic bacterial, viral, or fungal infection either during screening or prior to screening and not successfully resolved 4 weeks prior to screening visit
Participants with active or latent tuberculosis (confirmed within the 6 months prior to or during screening, by a positive screening test [interferon gamma release assay])
Resting oxygen saturation of < 89% using up to 4 L/min of supplemental oxygen at sea level and up to 6 L/min at altitude (>/= 5000 feet [1524 meters] above sea level) during screening
Class IV New York Heart Association chronic heart failure
Historical evidence of left ventricular ejection fraction < 35%
Presence of pulmonary hypertension that, in the investigator's opinion, would substantially limit the ability to comply with study requirements or may influence any of the safety or efficacy assessments included in the study
Cardiopulmonary rehabilitation program based on exercise training that has been completed within 8 weeks prior to screening or planned to start during the participant enrollment in this trial
History of smoking, alcohol or substance abuse disorder, or a malignancy
Previous treatment with PRM-151
Clinically significant abnormality on ECG during screening that, in the opinion of the investigator, may pose an additional risk in administering study drug to the participant including prolonged corrected QT interval > 450 ms (for men) or > 470 ms (for women) on ECG during screening based on the Fridericia correction formula
Clinically significant laboratory test abnormalities during screening (hematology, serum chemistry, and urinalysis) that, in the opinion of the investigator, may pose an additional risk in administering study drug to the participant
Pregnant or breastfeeding, or become pregnant during the study or within 8 weeks after the final dose of PRM-151
Women of childbearing potential (Only for participants enrolling in Japan)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zinpentraxin Alfa	PRM-151 (Zinpentraxin Alfa)	Participants will receive intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.
Placebo	Placebo	Participants will receive IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.

Primary Outcome Measures

Name	Time	Method
Absolute Change in Forced Vital Capacity (FVC [mL])	From Baseline up to Week 52

Secondary Outcome Measures

Name	Time	Method
Survival	From Baseline up to 1 year	Survival is measured by all-cause mortality
Time to Disease Progression	From Baseline up to 1 year
Absolute Change in FVC% Predicted	From Baseline up to Week 52
Absolute Change in 6-minute Walk Distance (6MWD)	From Baseline up to Week 52
Time to First Respiratory-related Hospitalizations	From Baseline up to 1 year
Change in Carbon Monoxide Diffusing Capacity (DLCO)	At Baseline, Week 12, Week 24, Week 36 and Week 52
Plasma Concentrations of PRM-151	Days 1, 5 and Weeks 4, 12, and 24
Prevalence of Anti-drug Antibodies (ADAs) at Baseline	At Baseline
Change in St. George Respiratory Questionnaire (SGRQ) Total Score	At Baseline, Week 12, Week 24, Week 36 and Week 52	The SGRQ is a 50-item respiratory-specific quality-of-life questionnaire. The questions assess the impact of disease on activity, functionality and symptoms. Each scale is scored from 0-100. A total score represents the weighted average of these three subscores. A lower score indicates best health while a higher score indicates worst health.
Percentage of Participants With Adverse Events (AEs)	From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year)
Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ)	At Baseline, Week 12, Week 24, Week 36 and Week 52	The UCSD-SOBQ is a 24-item questionnaire used to assess dyspnea severity during specific activities (21 items) and limitations caused by dyspnea in daily life (4 items). Items are assessed using a 6-point scale. Total scores, once summed, can range from 0-120 with a higher score reflecting greater dyspnea severity.
Time to First Acute Exacerbation of Idiopathic Pulmonary Fibrosis (IPF)	From Baseline up to 1 year
Percentage of Participants With Infusion-related Reactions (IRRs) and Other Adverse Events of Special Interest	From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year)
Percentage of Participants Permanently Discontinuing Study Treatment Due to AEs	From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year)
Percentage of Participants With ADAs During the Study	Days 1, 5 and Weeks 4, 12, 24, 36, 48, 52 and 56

Trial Locations

Locations (360): University of Alabama at Birmingham
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Birmingham, Alabama, United States
Banner University Medical Center Phoenix; Main Pharmacy
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Phoenix, Arizona, United States
Lovelace Scientific Resources, Inc.
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Phoenix, Arizona, United States
UC Irvine Medical Center
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Orange, California, United States
Stanford Hospital and Clinics
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Palo Alto, California, United States
University of California Davis
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Sacramento, California, United States
Inst. of Healthcare Assessment, Inc.
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San Diego, California, United States
UCSF Medical Center
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San Francisco, California, United States
Paloma Medical Group
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San Juan Capistrano, California, United States
William Sansum Diabetes Center
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Santa Barbara, California, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States