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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03538301
• Other study ID #: ND-L02-s0201-005
• Status: Completed
• Phase: Phase 2
• Start date: June 18, 2018
• Est. completion date: August 24, 2022

Study information

• Verified date: November 2023
• Source: Nitto Denko Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: August 24, 2022
• Est. primary completion date: August 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• ND-L02-s0201 (Low Dose)
Intravenous administration every 2 weeks
• ND-L02-s0201 (High Dose)
Intravenous administration every 2 weeks

Other:
• Other: Placebo
Saline

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Nitto Denko Corporation

Countries where clinical trial is conducted

United States,  Germany,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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