Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03451045

Enrollment

447

Registered

2018-03-01

Start date

2017-12-22

Completion date

2020-06-17

Last updated

2023-01-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis

Keywords

Pulmonary exacerbation, lenabasum, JBT-101

Brief summary

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.

Interventions

DRUGLenabasum 20 mg

Subjects will receive lenabasum 20 mg twice daily.

DRUGLenabasum 5 mg

Subjects will receive lenabasum 5 mg twice daily.

OTHERPlacebo

Subjects will receive placebo twice daily.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Intervention model description

Multicenter, double-blind, randomized, placebo-controlled, parallel group study.

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

Inclusion criteria

1. ≥ 12 years of age at the time Informed Consent/ Assent is signed. 2. Weight ≥ 40 kg. 3. FEV1 ≥ 40% predicted and \< 100% predicted in the last 12 months. 4. 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

1. Severe or unstable CF at screening or Visit 1. 2. Any of the following values for laboratory tests at screening: 1. A positive pregnancy test. 2. Hemoglobin \< 10 g/dL in males and \< 9 g/dL in females. 3. Neutrophils \< 1.0 x 10\^9 /L. 4. Platelets \< 75 x 10\^9/L. 5. Creatinine clearance \< 50 mL/min according to Modification of Diet in Renal Disease (MDRD) Study equation. 6. Serum transaminases \> 2.5 x upper limit of normal. 3. 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.

Design outcomes

Primary

Measure	Time frame	Description
Pulmonary Exacerbation (PEx) Rate Over 28 Weeks	28 weeks (Baseline Day 0 to Week 28)	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.

Secondary

Measure	Time frame	Description
Pulmonary Exacerbation (PEx) Rate	28 weeks (Baseline Day 0 to Week 28)	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
Time to First New Pulmonary Exacerbation (PEx)	28 weeks (Baseline Day 0 to Week 28)	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
Pulmonary Exacerbation (PEx)	28 weeks (Baseline Day 0 to Week 28)	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.
CFQ-R Respiratory Symptom Domain	28 weeks (Change from Baseline Day 0 to Week 28)	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.
FEV1 % Predicted	28 weeks (Change from Baseline Day 0 to Week 28)	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.

Countries

Austria, Belgium, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Spain, Sweden, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Lenabasum 20 mg BID Lenabasum 20 mg: Subjects will receive lenabasum 20 mg twice daily.	165
Lenabasum 5 mg BID Lenabasum 5 mg: Subjects will receive lenabasum 5 mg twice daily.	89
Placebo subjects received placebo BID	171
Total	425

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	7	1	3
Overall Study	any other reason	10	2	13
Overall Study	Lack of Efficacy	3	2	2
Overall Study	Non-compliance with study	2	0	1
Overall Study	Physician Decision	1	1	1
Overall Study	Pregnancy	0	0	2
Overall Study	Withdrawal by Subject	4	0	5

Baseline characteristics

Characteristic	Lenabasum 20 mg BID	Lenabasum 5 mg BID	Placebo	Total
Age, Continuous	26.2 years STANDARD_DEVIATION 9.08	28.9 years STANDARD_DEVIATION 11.24	26.6 years STANDARD_DEVIATION 10.81	26.9 years STANDARD_DEVIATION 10.5
Body Mass Index	21.07 kg/m^2 STANDARD_DEVIATION 3.179	22.26 kg/m^2 STANDARD_DEVIATION 4.164	21.52 kg/m^2 STANDARD_DEVIATION 3.931	21.50 kg/m^2 STANDARD_DEVIATION 3.728
CFTR Genotype F508del/F508del	83 Participants	34 Participants	74 Participants	191 Participants
CFTR Genotype F508del/other	56 Participants	38 Participants	70 Participants	164 Participants
CFTR Genotype Other/other or unknown	26 Participants	17 Participants	27 Participants	70 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	3 Participants	5 Participants	13 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	155 Participants	84 Participants	164 Participants	403 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants	2 Participants	2 Participants	9 Participants
FEV1 (L)	2.10 liters STANDARD_DEVIATION 0.73	2.20 liters STANDARD_DEVIATION 0.77	2.17 liters STANDARD_DEVIATION 0.75	2.15 liters STANDARD_DEVIATION 0.76
Number of Acute Pulmonary Exacerbations in Past Year five	6 Participants	4 Participants	10 Participants	20 Participants
Number of Acute Pulmonary Exacerbations in Past Year four	20 Participants	11 Participants	13 Participants	44 Participants
Number of Acute Pulmonary Exacerbations in Past Year one	1 Participants	0 Participants	1 Participants	2 Participants
Number of Acute Pulmonary Exacerbations in Past Year six or more	0 Participants	1 Participants	2 Participants	3 Participants
Number of Acute Pulmonary Exacerbations in Past Year three	63 Participants	30 Participants	69 Participants	162 Participants
Number of Acute Pulmonary Exacerbations in Past Year two	75 Participants	43 Participants	76 Participants	194 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) Black or African American	0 Participants	2 Participants	3 Participants	5 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	1 Participants	3 Participants	6 Participants
Race (NIH/OMB) White	161 Participants	86 Participants	163 Participants	410 Participants
Sex: Female, Male Female	91 Participants	44 Participants	93 Participants	228 Participants
Sex: Female, Male Male	74 Participants	45 Participants	78 Participants	197 Participants
Weight	58.41 kg STANDARD_DEVIATION 11.567	62.82 kg STANDARD_DEVIATION 15.54	59.25 kg STANDARD_DEVIATION 13.645	59.67 kg STANDARD_DEVIATION 13.39

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 165	0 / 89	0 / 171
other Total, other adverse events	151 / 165	80 / 89	151 / 171
serious Total, serious adverse events	50 / 165	25 / 89	50 / 171

Outcome results

Primary

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.

Time frame: 28 weeks (Baseline Day 0 to Week 28)