|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Cystic Fibrosis is a genetic disorder which results in thick mucus formation on the airways leading to increased lung infections,fibrosis of the lungs and digestive tract and abnormal immune function.
|Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To evaluate the efficacy of lenabasum 20 mg twice per day (BID) compared to placebo in the treatment of cystic fibrosis (CF) by assessing the rate of pulmonary exacerbations (PEx) using primary definition of PEx
|Secondary objectives of the trial
1. To evaluate the efficacy of lenabasum 20 mg BID compared to placebo in the treatment of CF by assessing other efficacy endpoints
2. To evaluate the efficacy of lenabasum 5 mg BID compared to placebo in the treatment of CF
1. To evaluate steady state plasma concentrations of lenabasum 20 mg and 5 mg BID at the estimated time of trough concentration after a dose of lenabasum
2. To evaluate plasma concentrations of lenabasum 20 mg and 5 mg at the estimated time of peak concentration after the first dose
3. To evaluate metabolites of lenabasum
4. To develop population pharmacokinetic models of lenabasum exposure in CF subjects
1. To evaluate safety of lenabasum 20 mg BID and lenabasum 5 mg BID treatment and placebo treatment
2. To evaluate tolerability of lenabasum 20 mg BID and lenabasum 5 mg BID treatment
|Trial contains a sub-study
|Principal inclusion criteria
|1. Documentation of a CF diagnosis as evidenced by 1 or more clinical features consistent with the CF phenotype and 1 or more of the following criteria:
a. Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
b. Two known disease-causing mutations in the CFTR gene.
2. Twelve years of age or older at the time Informed Consent/Assent is signed.
3. Weight ≥ 40 kg.
4. FEV1 ≥ 40% predicted and < 100 % predicted within the last 12 months.
5. Physician-initiated treatment with an IV antibiotic 2 or 3 times in the last 12 months for a new PEx.
6. As an alternative to inclusion criterion 5, 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.
7. Completion of the last course of antibiotics prescribed for any PEx ≥ 28 days before Visit 1.
8. Able to perform pulmonary function tests. Optional use of a bronchodilator before testing is allowed to facilitate testing if the bronchodilator is used consistently starting with Visit 1.
9. Willing to provide repeat sputum specimens. If a subject is unable to reliably spontaneously expectorate sputum, induced sputum collection is acceptable. Optional collection of induced sputum specimens is allowed if induced sputum specimens are consistently collected starting with Visit 1. Adolescents should try to produce sputum spontaneously and can opt out of sputum induction.
10. Willing not to use any cannabinoids or any illegal substance of abuse from screening through Visit 9.
11. Women of childbearing potential must not be pregnant or breastfeeding at Visit 1 and must be using at least one highly effective, or an acceptable method of contraception for at least 28 days before Visit 1 and be willing to continue to use at least one highly effective or an acceptable method of contraception throughout the study and for at least 28 days after discontinuation of study drug.
12. Male participants must be willing to follow contraceptive requirements and should not get anyone pregnant while they are taking the study product or within 28 days after taking the last dose of the study product, during which time period they or their partner must be willing to use at least one highly effective or an acceptable method of contraception.
13. Able to adhere to the study visit schedule and other protocol requirements.
|Principal exclusion criteria
|1. Severe or unstable CF at screening or Visit 1, such as:
a. Change in dose, or initiation of any new chronic therapy for CF lung disease within 28 days before Visit 1
b. Treatment with any systemic corticosteroids > 10 mg per day prednisone or equivalent within 14 days before Visit 1
c. Actively listed on an organ transplant list or have had an organ transplant other than corneal transplant.
2. Significant diseases or conditions other than CF that may influence response to the study drug or safety, such as:
a. Active hepatitis B or C infection
b. Human immunodeficiency virus infection
c. A history of cancer except basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ one year before Visit 1.
3. Subjects with a history of any seizure within the last 2 years
4. Pregnant, trying to become pregnant or lactating female.
5. Current evidence of alcohol abuse (defined as 4 or more drinks per day on at least 4 days of the week) or history of abuse of illegal and/or legally prescribed drugs such as barbiturates, benzodiazepines, amphetamines, cocaine, or opioids during the 1 year before screening.
6. Any investigational agent within 30 days or five therapeutic half-lives of that agent whichever is longer, before Visit 1
7. Any of the following values for laboratory tests at screening:
a. A positive pregnancy test
b. Hemoglobin < 10 g/dL in males and < 9 g/dL in females.
c. Neutrophils < 1.0 x 1000,000,000/L
d. Platelets < 75 x 1000,000,000/L
e. Creatinine clearance < 50 ml/min according to Modification of Diet in Renal Disease (MDRD) Study equation in adults and Schwartz eGFR formula in adolescent population
f. Serum transaminases > 2.5 x upper normal limit
8. Any other condition or concurrent medical therapy at screening or Visit 1 that causes the investigator to determine it is not safe for the subject to participate or that may influence response to study drug or interfere with study assessments.
|E.5 End points
|Primary end point(s)
|Rate of PEx using primary definition of PEx with lenabasum 20 mg BID, compared to placebo, during the treatment period
|Timepoint(s) of evaluation of this end point
|Visit 1 through study completion, up to 6 months
|Secondary end point(s)
|Efficacy (lenabasum 20 mg BID):
a. Event rate of PEx using secondary definition of PEx with lenabasum 20 mg BID compared to placebo
b. Time to first new PEx using primary definition of PEx with lenabasum 20 mg BID compared to placebo
c. Time to first PEx using secondary definition of PEx with lenabasum 20 mg BID compared to placebo
d. Change from baseline in CFQ-R respiratory symptom domain with lenabasum 20 mg BID compared to placebo
e. Change from baseline in FEV1 % predicted with lenabasum 20 mg BID compared to placebo
Efficacy (lenabasum 5 mg BID):
a. Rate of pulmonary exacerbations (PEx) using primary definition of PEx with lenabasum 5 mg BID compared to placebo, during the treatment period
b. Event rate of PEx using secondary definition of PEx with lenabasum 5 mg BID compared to placebo
c. Time to first new PEx using primary definition of PEx with lenabasum 5 mg BID compared to placebo
d. Time to first PEx using secondary definition of PEx with lenabasum 5 mg BID compared to placebo
e. Change from baseline in CFQ-R respiratory symptom domain with lenabasum 5 mg BID compared to placebo
f. Change from baseline in FEV1 % predicted with lenabasum 5 mg BID compared to placebo
1. Estimated trough plasma concentrations of lenabasum
2. Estimated maximum plasma concentration (Cmax) of lenabasum
3. Metabolites of lenabasum
1. Treatment emergent adverse events (TEAEs)
2. Changes in vital signs, physical examination, blood and urine laboratory safety tests and electrocardiograms
3. Treatment discontinuations with lenabasum treatments compared to placebo
|Timepoint(s) of evaluation of this end point
|Efficacy and Safety endpoints: Visit 1 through study completions, up to 6 months;
PK endpoints: Visit 1 through Visit 8.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years