A study of safety and efficacy of lenabasum in Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 8 March 2021
• Main ID: EUCTR2017-003723-29-DE
• Date of registration: 14/02/2018
• Prospective Registration: Yes
• Primary sponsor: Corbus Pharmaceuticals, Inc.
• Public title: A study of safety and efficacy of lenabasum in Cystic Fibrosis
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis - A Phase 2 safety and efficacy study of Lenabasum in Cystic Fibrosis
• Date of first enrolment: 19/11/2018
• Target sample size: 415
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003723-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, Czech Republic, Czechia, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Portugal, Réunion, Romania, Russian Federation, Serbia, Slovakia, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Regulatory Services
• Affiliation: TMC Pharma Services Ltd

• Name: Regulatory Services
• Affiliation: TMC Pharma Services Ltd

Key inclusion & exclusion criteria

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 (failure rate < 1% per year) 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 62
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 353
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic Fibrosis (CF)
MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Lenabasum
Product Code: JBT-101
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENABASUM
CAS Number: 137945-48-3
Current Sponsor code: JBT-101
Other descriptive name: resunab, ajulemic acid, anabasum
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Lenabasum
Product Code: JBT-101
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENABASUM
CAS Number: 137945-48-3
Current Sponsor code: JBT-101
Other descriptive name: resunab, ajulemic acid, anabasum
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Visit 1 through study completion, up to 6 months

Primary end point(s): Rate of PEx using primary definition of PEx with lenabasum 20 mg BID, compared to placebo, during the treatment period

Main Objective: 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 Objective: Efficacy:
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
Pharmacokinetic:
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
Safety:
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

Secondary Outcome(s)

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.

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
Pharmacokinetics:
1. Estimated trough plasma concentrations of lenabasum
2. Estimated maximum plasma concentration (Cmax) of lenabasum
3. Metabolites of lenabasum
Safety:
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

Secondary ID(s)

JBT101-CF-002

2017-003723-29-GB

Source(s) of Monetary Support

Corbus Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 19/11/2018
Contact: