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

• ClinicalTrials.gov Identifier: NCT04552899
• Recruitment Status: Completed
• First Posted: September 17, 2020
• Last Update Posted: May 15, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 14, 2020
• First Posted Date: September 17, 2020
• Last Update Posted Date: May 15, 2023
• Actual Study Start Date: March 19, 2021
• Actual Primary Completion Date: February 10, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 16, 2020): Absolute Change in Forced Vital Capacity (FVC [mL]) [ Time Frame: From Baseline up to Week 52 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 9, 2022)

• Absolute Change in 6-minute Walk Distance (6MWD) [ Time Frame: From Baseline up to Week 52 ]
• Absolute Change in FVC% Predicted [ Time Frame: From Baseline up to Week 52 ]
• Time to Disease Progression [ Time Frame: From Baseline up to 2.5 years ]
• Time to First Respiratory-related Hospitalizations [ Time Frame: From Baseline up to 2.5 years ]
• Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) [ Time Frame: From Baseline up to Week 52 ]
• Change in St. George Respiratory Questionnaire (SGRQ) Total Score [ Time Frame: From Baseline up to Week 52 ]
• Time to First Acute Exacerbation of Idiopathic Pulmonary Fibrosis (IPF) [ Time Frame: From Baseline up to 2.5 years ]
• Change in Carbon Monoxide Diffusing Capacity (DLCO) [ Time Frame: From Baseline up to Week 52 ]
• Survival [ Time Frame: From Baseline up to 2.5 years ]
  Survivial is measured by all-cause mortality
• Percentage of Participants with Adverse Events (AEs) [ Time Frame: From Baseline up to 2.5 years ]
• Percentage of Participants with Infusion-related Reactions (IRRs) and Other Adverse Events of Special Interest [ Time Frame: From Baseline up to 2.5 years ]
• Percentage of Participants Permanently Discontinuing Study Treatment due to AEs [ Time Frame: From Baseline up to 2.5 years ]
• Change from Baseline in Targeted Clinical Laboratory Test Results [ Time Frame: From Baseline up to 2.5 years ]
• Plasma Concentrations of PRM-151 [ Time Frame: Days 1, 5 and Weeks 4, 12, 24, 36, 48, 52 and 56 ]
• Prevalence of Anti-drug Antibodies (ADAs) at Baseline [ Time Frame: Day 1 ]
• Percentage of Participants with ADAs During the Study [ Time Frame: Days 1, 5 and Weeks 4, 12, 24, 36, 48, 52 and 56 ]

Original Secondary Outcome Measures (submitted: September 16, 2020)

• Absolute Change in 6-minute Walk Distance (6MWD) [ Time Frame: From Baseline up to Week 52 ]
  6MWD is the distance covered by the patient during the 6-minute walk test.
• Absolute Change in FVC% Predicted [ Time Frame: From Baseline up to Week 52 ]
• Progression-free Survival (PFS) [ Time Frame: From Baseline up to 2.5 years ]
  PFS is defined as the time to first occurrence of >= 10% absolute decline in % predicted FVC, >= 15% relative decline in 6MWD, or death
• Time to First Respiratory-related Hospitalizations [ Time Frame: From Baseline up to 2.5 years ]
  Respiratory-related Hospitalizations are defined as non-elective hospitalizations due to any respiratory cause, including acute exacerbations of IPF, or suspected acute exacerbations of IPF, as determined by Adjudication Committee)
• Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) [ Time Frame: From Baseline up to Week 52 ]
  The UCSD-SOBQ consists of 24 questions in 2 domains: to assess dyspnea severity during specific activities (21 items) and limitations caused by dyspnea in daily life (4 items). Each questions is assessed using a 6-point Likert scale and summed to produce a total score ranging from 0-120. Higher scores reflect greater dyspnea severity.
• Change in St. George Respiratory Questionnaire (SGRQ) Total Score [ Time Frame: From Baseline up to Week 52 ]
  The SGRQ consists of 50 questions in 3 domains: the impact of disease on symptoms (severity of respiratory symptoms), activity (impariment in participant activity), and functionality (effects of respiratory symptoms on overall function and well-being). Each scale is scored from 0 to 100, and a total score represents the weighted average of these three subscores. Items are assessed on various response scales, including a 5-point Likert scale and a true/false scale. The SGRQ has a recall period of the past 4 weeks.
• Time to First Acute Exacerbation of Idiopathic Pulmonary Fibrosis (IPF) [ Time Frame: From Baseline up to 2.5 years ]
• Change in Carbon Monoxide Diffusing Capacity (DLCO) [ Time Frame: From Baseline up to Week 52 ]
• Survival [ Time Frame: From Baseline up to 2.5 years ]
  Survivial is measured by all-cause mortality
• Incidence and Severity of Adverse Events (AEs) [ Time Frame: From Baseline up to 2.5 years ]
  Severity will be determined according to the 5-point severity scale (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 [NCI CTCAE, v.5.0].
• Incidence and Severity of Infusion-related Reactions (IRRs) and Other Adverse Events of Special Interest [ Time Frame: From Baseline up to 2.5 years ]
• Percentage of Participants Permanently Discontinuing Study Treatment due to AEs [ Time Frame: From Baseline up to 2.5 years ]
• Change from Baseline in Targeted Clinical Laboratory Test Results [ Time Frame: From Baseline up to 2.5 years ]
• Serum Concentrations of PRM-151 [ Time Frame: Days 1, 5 and Weeks 4, 12, 24, 36, 48, 52 and 56 ]
• Prevalence of Anti-drug Antibodies (ADAs) at Baseline [ Time Frame: Day 1 ]
• Incidence of ADAs During the Study [ Time Frame: Days 1, 5 and Weeks 4, 12, 24, 36, 48, 52 and 56 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis
• Official Title: A Phase III Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of PRM-151 in Patients With Idiopathic Pulmonary Fibrosis
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Idiopathic Pulmonary Fibrosis

Intervention

• Drug: PRM-151 (Zinpentraxin Alfa)
  A 10 mg/kg IV infusion of PRM-151 based on the participants weight will be administered on Days 1, 3 and 5 followed by infusions Q4W to Week 48.
• Drug: Placebo
  Placebo matching PRM-151 will be administered by IV infusion on Days 1, 3 and 5, followed by infusions Q4W to Week 48.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 13, 2022): 665
• Original Estimated Enrollment (submitted: September 16, 2020): 658
• Actual Study Completion Date: February 10, 2023
• Actual Primary Completion Date: February 10, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Peru, Puerto Rico, Russian Federation

Administrative Information

• NCT Number: NCT04552899
• Other Study ID Numbers: WA42293; 2020-000791-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023