JUNIPER: A Phase 2 Study to Evaluate the Safety, Biological Activity, and PK of ND-L02-s0201 in Subjects With IPF

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Biological Activity, and PK of ND-L02-s0201 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

A phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety, tolerability, biological activity, and pharmacokinetics (PK) of ND-L02-s0201 for Injection in subjects with IPF.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Other: Other: Placebo; Drug: ND-L02-s0201 (Low Dose); Drug: ND-L02-s0201 (High Dose)

Detailed Description

All subjects were treated with ND-L02-s0201 or placebo for 24 weeks (a total of 12 doses). Subject's participation in the study was approximately 40 weeks including a Screening and Baseline period of up to 6 weeks, a treatment period of 24 weeks (including the 2 weeks after the last study treatment), and a follow-up period of 10 weeks after End-of-Treatment (EOT).

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69126
      • Thoraxklinik-Heidelberg gGmbH
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
      • Universitätsklinikum Freiburg
  • Hesse
    • Immenhausen, Hesse, Germany, 34376
      • Lungenfachklinik Immenhausen
  • Hessen
    • Giessen, Hessen, Germany, 35392
      • Justus-Liebig-Universitaet Giessen
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover (MHH)
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, NRW 45239
      • Ruhrlandklinik, Universitatmedzin Essen
• Japan
  • Hyogo
    • Himeji-Shi, Hyogo, Japan, 670-8520
      • National Hospital Organization Himeji Medical Center
  • Ibaraki
    • Naka-gun, Ibaraki, Japan, 319-1113
      • National Hospital Organization Ibarakihigashi National Hospital
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center
  • Sakai-shi
    • Osaka, Sakai-shi, Japan, 5918555
      • National Hospital Organization Kinki-Chuo Chest Medical Center
  • Seto-shi
    • Aichi, Seto-shi, Japan, 489-8642
      • Tosei General Hospital
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0AY
      • Royal Papworth Hospital NHS Foundation Trust
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-0001
      • Banner-University Medical Center Tucson Campus
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Northridge, California, United States, 91324
      • Amicis Research Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco, Medical Center at Parnassus
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, PA
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61637
      • OSF HealthCare Saint Francis Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40218
      • Norton Clinical Research Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical School
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center (DHMC)
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio: First Outpatient Research Unit
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
  • Washington
    • Seattle, Washington, United States, 98195-0001
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Forced vital capacity (FVC) ≥ 45% of predicted.
• Diffusion capacity of the lung for carbon monoxide (DLco) corrected for hemoglobin ≥ 30% of predicted value
• Ratio of forced expiratory volume in 1 second (FEV1) to FVC ≥ 0.70.

Exclusion Criteria:

• Best, acceptable FVC from separate screening spirometry that differ by ≥ 200 mL.
• Respiratory exacerbation(s) or hospitalization for IPF exacerbation within 3 months before screening.
• Anticipated to receive a lung transplant during the subject's participation in the study.
• Active smoker or smoking cessation within 12 weeks before screening.
• Malignancy within the last 5 years, with the exception of curable cancer that has received adequate treatment.
• Evidence of any unstable or untreated, clinically significant disease or condition that, in the opinion of the Investigator, might confound the interpretation of the study or place the subject at increased risk.
• Treatment with high dose corticosteroids, cytotoxic agents, unapproved IPF targeted therapy, and cytokine modulating agents within 8 weeks or 5 half-lives (whichever is longer) before screening
• Participation in an investigational study with the last dose of investigational product occurring within 8 weeks or 5 half-lives (whichever is longer) before screening.
• Pregnant or breastfeeding.
• Medical history of infection with HIV, hepatitis B, or hepatitis C.
• History of alcohol abuse and/or dependence within the last 2 years.
• History within the last 2 years of significant mental illness, or physical dependence on any opioid or illicit drugs.

Other protocol defined inclusion/exclusion criteria could apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; ND-L02-s0201 45mg	Drug: ND-L02-s0201 (Low Dose); Intravenous administration every 2 weeks; Other Names: 45mg
Experimental: Dose Level 2; ND-L02-s0201 90mg	Drug: ND-L02-s0201 (High Dose); Intravenous administration every 2 weeks; Other Names: 90mg
Placebo Comparator: Placebo; Control Arm	Other: Other: Placebo; Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Discontinuing Study Treatment Due to TEAEs	The number of participants with TEAEs leading to discontinuation from the study treatment. The Safety Population (including all participants who received at least one dose of study treatment) is presented. TEAE = treatment-emergent adverse event	Change in the incidence and severity of adverse events related to study treatment from baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Decline in FVC From Baseline to Week 24	Slope in FVC from Baseline to Week 24 (measured in L/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. FVC = forced vital capacity	Baseline to Week 24
Rate of Decline in ppFVC From Baseline to Week 24	Slope in ppFVC from Baseline to Week 24 (measured in %/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. ppFVC = percent predicted forced vital capacity	Baseline to Week 24
Absolute and Relative Change in FVC (L) From Baseline to Week 24	Absolute and Relative Change in FVC (L) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity	Baseline to Week 24
Percent Change in FVC From Baseline to Week 24	Percent Change in FVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity	Baseline to Week 24
Absolute and Relative Change in ppFVC (%) From Baseline to Week 24	Absolute and Relative Change in ppFVC (%) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity	Baseline to Week 24
Percent Change in ppFVC From Baseline to Week 24	Percent Change in ppFVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity	Baseline to Week 24
Summary of Study Treatment Response of FVC	Proportion of participants with an FVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, more than 5% to less than or equal to 10%, and more than 10% at Visit 14 (Day 169). Participants with an FVC response were defined as improvement in FVC (ie, FVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity	Baseline to Visit 14 (Day 169)
Summary of Study Treatment Response of ppFVC	Proportion of participants with an ppFVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, greater than 5% to less than or equal to 10%, and greater than 10% at Visit 14 (Day 169). Participants with an ppFVC response were defined as improvement in ppFVC (ie, ppFVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity	Baseline to Visit 14 (Day 169)
Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24	Change in diffusion capacity of the lung for carbon monoxide (DLCO) and DLCO corrected for hemoglobin (mL/min/mmHg) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented.	Baseline to Week 24
Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT	Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature [Baseline to Week 24]), as determined by qualitative assessment (central radiologist) and quantitative analysis (Quantitative Lung Fibrosis - QLF analysis). Quantitative HRCT parameters included the following: Quantitative Lung Fibrosis (QLF) score (% of whole lung field volume); Ground glass opacity (GGO) (% of whole lung field volume); Reticulation (% of whole lung field volume); Honeycombing (% of whole lung field volume); Normal lung (% of whole lung field volume); Emphysema (low attenuation area [LAA]; % of whole lung field volume) The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented.	Baseline to Week 24
Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT	Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature [Baseline to Visit 14 (Day 169)]), as determined by qualitative assessment (central radiologist). The Likert scale values are included in the descriptions presented. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) with HRCT assessment at Visit 14/Early Termination is presented.	Baseline to Visit 14 (Day 169)
Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation	Total number of events of participants who experienced idiopathic pulmonary fibrosis (IPF) exacerbation (ie, an unexplained worsening of dyspnea, evidence of hypoxemia as defined by worsened or severely impaired gas exchange, new radiographic alveolar infiltrates, and an absence of an alternative explanation such as infection, pulmonary embolism, pneumothorax, or heart failure) or death (weeks).	Baseline to study completion, up to Day 239
Events of Hospitalization for Respiratory Ailments or Death	Events (participants who experienced hospitalization for respiratory ailments or died) for respiratory ailments are presented. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented.	up to 12 weeks after the end of study treatment
Total Events of Death Due to All Causes	Rate of mortality due to all causes is presented. Overall survival was defined as the time from start of study treatment to death due to any cause.	up to 12 weeks after the end of study treatment
Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation	Events of deterioration of Idiopathic Pulmonary Fibrosis (IPF) resulting in lung transplantation (LP; up to 12 weeks after the end of study treatment) or death (weeks) and rate of deterioration of IPF resulting in lung transplantation (up to 12 weeks after the end of study treatment) are presented. Total events = Participants who experience deterioration of IPF resulting in LP (or died). Rate of Deterioration = Rate of Deterioration of IPF Resulting in LP.	Baseline to 12 weeks after end of study treatment

Collaborators and Investigators

• Sponsor: Nitto Denko Corporation
• Investigators: Study Director: Nitto Denko Corporation, Nitto Denko Corporation

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2018
• Primary Completion (Actual): August 24, 2022
• Study Completion (Actual): August 24, 2022

Study Registration Dates

• First Submitted: May 2, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: ND-L02-s0201-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No