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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: ND-L02-s0201 (Low Dose)
* Drug: ND-L02-s0201 (High Dose)
* Other: Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |