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

Phase 2

Completed

Conditions: Idiopathic Pulmonary Fibrosis

Interventions: Drug: ND-L02-s0201 (Low Dose)
Drug: ND-L02-s0201 (High Dose)

Registration Number: NCT03538301

Lead Sponsor: Nitto Denko Corporation

Brief Summary: 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.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 123

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose Level 1	ND-L02-s0201 (Low Dose)	ND-L02-s0201 45mg
Dose Level 2	ND-L02-s0201 (High Dose)	ND-L02-s0201 90mg

Primary Outcome Measures

Name	Time	Method
Number of Participants Discontinuing Study Treatment Due to TEAEs	Change in the incidence and severity of adverse events related to study treatment from baseline to 24 weeks	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

Secondary Outcome Measures

Name	Time	Method
Rate of Decline in FVC From Baseline to Week 24	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
Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation	Baseline to 12 weeks after end of study treatment	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.
Percent Change in FVC From Baseline to Week 24	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
Summary of Study Treatment Response of FVC	Baseline to Visit 14 (Day 169)	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
Quantitative Changes of Interstitial Lung Abnormalities as Measured by HRCT	Baseline to Week 24	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.
Rate of Decline in ppFVC From Baseline to Week 24	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
Absolute and Relative Change in FVC (L) From Baseline to Week 24	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
Absolute and Relative Change in ppFVC (%) From Baseline to Week 24	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
Events of Hospitalization for Respiratory Ailments or Death	up to 12 weeks after the end of study treatment	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.
Change in DLCO and DLCO Corrected for Hemoglobin From Baseline to Week 24	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.
Qualitative Changes of Interstitial Lung Abnormalities as Measured by HRCT	Baseline to Visit 14 (Day 169)	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.
Total Events of Death Due to All Causes	up to 12 weeks after the end of study treatment	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.
Percent Change in ppFVC From Baseline to Week 24	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
Summary of Study Treatment Response of ppFVC	Baseline to Visit 14 (Day 169)	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
Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation	Baseline to study completion, up to Day 239	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).

Trial Locations

Locations (33): Norton Clinical Research Group
🇺🇸
Louisville, Kentucky, United States
Thoraxklinik-Heidelberg gGmbH
🇩🇪
Heidelberg, Baden-Wuerttemberg, Germany
Justus-Liebig-Universitaet Giessen
🇩🇪
Giessen, Hessen, Germany
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
University of Minnesota Medical School
🇺🇸
Minneapolis, Minnesota, United States
UT Health San Antonio: First Outpatient Research Unit
🇺🇸
San Antonio, Texas, United States
Amicis Research Center
🇺🇸
Northridge, California, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Dartmouth-Hitchcock Medical Center (DHMC)
🇺🇸
Lebanon, New Hampshire, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
National Hospital Organization Himeji Medical Center
🇯🇵
Himeji-Shi, Hyogo, Japan
Ruhrlandklinik, Universitatmedzin Essen
🇩🇪
Essen, North Rhine-Westphalia, Germany
University of California, San Francisco, Medical Center at Parnassus
🇺🇸
San Francisco, California, United States
University of Utah Health
🇺🇸
Salt Lake City, Utah, United States
Duke University Hospital
🇺🇸
Durham, North Carolina, United States
Central Florida Pulmonary Group, PA
🇺🇸
Orlando, Florida, United States
Mayo Clinic Florida
🇺🇸
Jacksonville, Florida, United States
OSF HealthCare Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
University of Washington
🇺🇸
Seattle, Washington, United States
National Hospital Organization Ibarakihigashi National Hospital
🇯🇵
Naka-gun, Ibaraki, Japan
Kanagawa Cardiovascular and Respiratory Center
🇯🇵
Yokohama-shi, Kanagawa, Japan
Penn State Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Lungenfachklinik Immenhausen
🇩🇪
Immenhausen, Hesse, Germany
Medizinische Hochschule Hannover (MHH)
🇩🇪
Hannover, Lower Saxony, Germany
National Hospital Organization Kinki-chuo Chest Medical Center
🇯🇵
Osaka, Sakai-shi, Japan
Royal Papworth Hospital NHS Foundation Trust
🇬🇧
Cambridge, Cambridgeshire, United Kingdom
Banner-University Medical Center Tucson Campus
🇺🇸
Tucson, Arizona, United States
Tosei General Hospital
🇯🇵
Aichi, Seto-shi, Japan
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Universitatsklinikum Freiburg
🇩🇪
Freiburg, Baden-Württemberg, Germany