Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis

Study Overview
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Brief Summary
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This is a Phase 2 multicenter, double-blind, randomized, placebo-controlled study assessing the efficacy and safety of lenabasum for the treatment of cystic fibrosis in patients 12 years of age or older. Approximately 415 subjects will be enrolled in this study at about 100 sites in North America, and Europe. The planned duration of treatment with study drug is 28 weeks. Study drug will be lenabasum 20 mg BID, lenabasum 5 mg BID, and placebo in a 2:1:2 ratio.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Lenabasum 20 mg
* Drug: Lenabasum 5 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 12 years of age at the time Informed Consent/ Assent is signed. Weight ≥ 40 kg. FEV1 ≥ 40% predicted and < 100% predicted in the last 12 months. Physician-initiated treatment with an IV antibiotic 2 or 3 times in the last 12 months for a new PEx or physician-initiated treatment with an IV antibiotic 1 time in the last 12 months plus physician-initiated treatment with oral antibiotic(s) 1 or more times in the past 12 months for a new PEX. Exclusion Criteria: Severe or unstable CF at screening or Visit 1. Any of the following values for laboratory tests at screening: A positive pregnancy test. Hemoglobin < 10 g/dL in males and < 9 g/dL in females. Neutrophils < 1.0 x 10^9 /L. Platelets < 75 x 10^9/L. Creatinine clearance < 50 mL/min according to Modification of Diet in Renal Disease (MDRD) Study equation. Serum transaminases > 2.5 x upper limit of normal. Any medical condition or concurrent medical therapies at screening or Visit 1 that may put the subject at greater safety risk, influence response to study drug or interfere with study assessments.

Ages Eligible for Study
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Minimum Age: 12 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
Interventional Model Description: Multicenter, double-blind, randomized, placebo-controlled, parallel group study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenabasum 20 mg BID<br> | Drug: Lenabasum 20 mg<br>* Subjects will receive lenabasum 20 mg twice daily.<br>|
| Experimental: Lenabasum 5 mg BID<br> | Drug: Lenabasum 5 mg<br>* Subjects will receive lenabasum 5 mg twice daily.<br>|
| Placebo Comparator: Placebo BID<br> | Other: Placebo<br>* Subjects will receive placebo twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Exacerbation (PEx) Rate Over 28 Weeks | Rate of PEx using the primary PEx definition with lenabasum 20 mg BID compared to placebo, during the treatment period. An primary PEx is defined on the physician's decision to treat with oral, intraveneous or inhaled antibiotics in the presence 4/12 Fuch's criteria (Change in sputum, new/increased hemoptysis, increased cough, increased dyspnea, malaise, fatigue/lethargy, Temperature greater than 38C, weight loss, sinus pain, change in sinus discharge, change in exam of chest, decrease in FEV1 of more than 10%, radiographic change). This excludes prophylactic antibiotics. A new PEx is a one that occurs at 28 days after the previous PEx. | 28 weeks (Baseline Day 0 to Week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Exacerbation (PEx) Rate | Event rate of PEx using the secondary PEx definition with lenabasum 20 mg BID compared to placebo. The secondary definition of a PEx is based on the physician's diagnosis of pulmonary exacerbation and commencement of new oral, intravenous, or inhaled antibiotics. A new PEx is defined one that starts 28 or more days after the previous confirmed PEx. The PEx rate is calculated as the number of PEx/28 weeks | 28 weeks (Baseline Day 0 to Week 28) | 
| Time to First New Pulmonary Exacerbation (PEx) | Time to first new PEx using the primary PEx definition with lenabasum 20 mg BID compared to placebo. An primary PEx is defined on the physician's decision to treat with oral, intraveneous or inhaled antibiotics in the presence 4/12 Fuch's criteria (Change in sputum, new/increased hemoptysis, increased cough, increased dyspnea, malaise, fatigue/lethargy, Temperature greater than 38C, weight loss, sinus pain, change in sinus discharge, change in exam of chest, decrease in FEV1 of more than 10%, radiographic change). This excludes prophylactic antibiotics. A new PEx is a one that occurs at 28 days after the previous PEx. The rate is calculate over a 28 week period from visit 1 to week 28 visit | 28 weeks (Baseline Day 0 to Week 28) | 
| Pulmonary Exacerbation (PEx) | Time to first PEx using the secondary PEx definition with lenabasum 20 mg BID compared to placebo. The secondary definition of a PEx is based on the physician's diagnosis of pulmonary exacerbation and commencement of new oral, intravenous, or inhaled antibiotics. A new PEx is defined one that starts 28 or more days after the previous confirmed PEx. | 28 weeks (Baseline Day 0 to Week 28) | 
| CFQ-R Respiratory Symptom Domain | Cystic Fibrosis Questionnaire - Revised measures change from baseline in CFQ-R respiratory symptom domain with lenabasum compared to placebo. Subjects >/= 14 years of age. 5 distinct 4-point Likert scales (e.g., always/often/ sometime/never) Scores for each HRQoL domain; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health. | 28 weeks (Change from Baseline Day 0 to Week 28) | 
| FEV1 % Predicted | Change from baseline to week 28 in Forced Expiratory Volume in 1 second (FEV1) expressed as a percentage of a normal range. A lower percentage FEV1 is indicative of decrease in lung functionality. The changes observed from baseline to week 28 for lenabasum will be compared with those observed for placebo treated participants. | 28 weeks (Change from Baseline Day 0 to Week 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary exacerbation, lenabasum, JBT-101