A Phase 2 safety and efficacy study of JBT101 in cystic fibrosis
Research type
Research Study
Full title
A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of JBT-101 in Cystic Fibrosis
IRAS ID
188235
Contact name
Damian Downey
Contact email
Sponsor organisation
Corbus Pharmaceuticals, Inc.
Eudract number
2015-002581-23
Duration of Study in the UK
0 years, 11 months, 2 days
Research summary
Research Summary
New treatments are needed to reduce chronic inflammation and scarring and help clear bacteria in cystic fibrosis (CF). The genetic mutation that causes CF leads to thick secretions that obstruct the lungs and other organs. The immune system in CF is overactive, but inefficient at clearing bacteria. These problems generate a vicious cycle of obstruction, infection and inflammation/scarring that causes organ dysfunction and even death from CF.JBT-101 is a man-made drug that is structurally related to marijuana, but doesn’t have marijuana’s unwanted effects on the brain. JBT-101 increases production of molecules that stimulate a naturally-occurring network to resolve inflammation, stop scarring, and increase bacterial clearance. This research will test whether JBT-101 has acceptable safety and shows trends for clinical benefit in 70 adult participants with stable CF, when administered orally for 84 days in doses up to 20 mg twice a day. There is no guarantee of benefit to the participant. This study is designed to obtain information to guide the design of additional Phase 2 and Phase 3 studies to test efficacy of JBT-101 in CF.
This research will be conducted at about 24 CF out-patient care centres at academic medical institutions in Europe, Israel and United States and is funded by Corbus Pharmaceuticals, Inc.
Participants must have CF, be ≥ 18 and ≤ 65 years old, and have a lung function measurement (FEV1) that is ≥ 40% predicted value. Screening takes ≤ 28 days, and study participation takes 112 days (84 days treatment and 28 days follow-off). Based on random assignment, 50 participants will receive JBT-101 at some time during the study, and 20 participants will receive placebo (inactive material) throughout.
Study procedures include questionnaires, medical history, vital signs, physical examination, lung function tests, sputum, blood, and urine tests, and electrocardiograms. Participants will be asked about side effects.
Summary of Results
General information about the trial
Where did the study take place:
This study took place in the following countries (number of patients):
• United States (47)
• Poland (30)
• United Kingdom (6)
• Germany (3)
• Italy (3)When did the study take place:
The study started in 29 September 2015 and ended in 28 December 2016.Why was this study done?
The sponsor is testing lenabasum in people with cystic fibrosis (CF).
The study summarised here was done to find out if lenabasum was safe to give to people with CF and to test its effect on how well the people with CF were feeling and functioning.
This was a randomised, double-blind, placebo-controlled study; which means that neither the person in the study nor the person’s doctor knew if the person was taking the drug (lenabasum) or a placebo. This type of study, where no-one in the study is aware of which drug a person is taking, is usually considered the best and fairest test of the safety and effectiveness of a new medicine. A placebo is a treatment that has no active effect on the person and is used as a standard for comparison to the test drug. All study drug and placebo taken in this study were provided as identical capsules to be swallowed.General information about the disease
All people in this study had CF. CF is a genetic disease that some people are born with and causes the build-up of thick sticky mucus in the lungs, digestive system, and other organs of the body. People with CF have inflammation in the lungs that can worsen when they develop lung infections. The major cause of death in people with CF is worsening of their chronic lung disease.
A pulmonary exacerbation is a sudden worsening of the person’s day-to-day symptoms of lung disease, often caused by an infection. Symptoms include coughing, producing more sputum (a mix of saliva and mucus coughed up from the lungs), and shortness of breath due to increased inflammation of the lungs. Pulmonary exacerbations lead to reduced survival in people with CF, a gradual loss of lung function, and reduced quality of life. Exacerbations may also lead to an increase in the use of antibiotics or a longer time on antibiotics, less time between episodes of severe symptoms, as well as reduced lung function.
Drugs such as ibuprofen or steroids taken by mouth are sometimes used to try to reduce inflammation, but these may have serious side effects and are not prescribed as a regular treatment for most people with CF.
General information about the new treatment, lenabasum What medicine was studied?Lenabasum (also called JBT-101 or anabasum, and previously called Resunab) is a drug being tested for its ability to reduce the numbers of pulmonary exacerbations by reducing inflammation people with CF experience. Lenabasum works on proteins called cannabinoid receptors to reduce inflammation without suppressing the immune system. It may reduce inflammation in people with CF and as a result reduce how often pulmonary exacerbations occur or reduce their severity.
Who was in the study?
Overall, 89 men and women with CF were enrolled and 85 aged 18 to 62 years were treated during the study. People with severe or unstable CF were not allowed to take part.
People in this study were treated with 1 mg or 5 mg lenabasum once a day for 4 weeks, or placebo. After the first 4 weeks, people were treated with 20 mg or 40 mg lenabasum daily, or placebo, for a further 8 weeks. In total, 61 people took lenabasum daily and 24 people took only a placebo.
The analysis compared all 61 patients treated with lenabasum to 24 patients treated with placebo.
How long were patients in the study?
The patients were treated for 12 weeks.Safety of lenabasum
A side effect is an unwanted effect (e.g. headache) that happen during the study. The safety of a new drug is estimated by looking at the numbers of patients with side effects that might be related to the treatments in the study. These side effects are also called “adverse reactions”. Serious adverse reactions (serious side effects) are the worst type of side effect. Patients with serious side effects may have to go to hospital, or stay longer in hospital than was planned, and the side effects may be life-threatening or even fatal.
To find out what the side effects of lenabasum are, the doctors did medical tests on the patients before and after starting treatment in the study and also asked them how they were feeling. Serious and other side effects related to lenabasum are listed below.What were the serious side effects of lenabasum?
To find out what the side effects of lenabasum are, the doctors did medical tests on the patients before and after starting treatment in the study and also asked them how they were feeling.Serious side effects:
There were no serious side effects related to the study treatment in this study.
There were no deaths in this study.
Other side effects on lenabasum:
Other side effects related to the study treatment (that were not serious) in the 61 patients treated with lenabasum included:
• Dry mouth: 7 of 61 patients (11.4%)
• Cognitive disorder (noticeably reduced mental ability): 2 of 61 patients (3.2%)
• Nervous system disorder (difficulty focusing): 2 of 61 (3.2%)
• Depressed mood: 2 of 61 (3.2%)
• Feeling abnormal: 2 of 61 patients (3.2%)
• Memory impairment: 2 of 61 (3.2%)
• Apathy (lack of interest or enthusiasm): 1 of 61 (1.6%)
• Dizziness: 1 of 61 patients (1.6%)
• Pain in extremity (pain in arm or leg): 1 of 61 (1.6%)
Safety summary:
Lenabasum was safe and well tolerated in this study. There were no deaths reported, and no new safety signals were identified. There were no serious side effects related to lenabasum.
The most common side effect for people treated with lenabasum was dry mouth. All other side effects were reported by at most 2 people treated with lenabasum.Overall results of the study
Is lenabasum effective in treatment patients with cystic fibrosis?
A total of 85 adolescents and adults with CF from the United States, Germany, Italy, Poland, and the United Kingdom were treated in this study were treated with lenabasum (61 patients) or placebo (24 patients).
The assessment of the efficacy of lenabasum in CF in this study was based on comparing the numbers of people with CF lung problems after 12 weeks of treatment compared with people treated with placebo. Efficacy evaluations were comparable for lenabasum and placebo (this means there was no significant difference between lenabasum and placebo in this study). Other assessments of efficacy also showed no significant difference to placebo. The changes in measures of lung function (such as the amount of air exhaled in one second) were similar for people treated with lenabasum and people treated with placebo.
Lenabasum was safe and well tolerated in this study. There were no deaths or serious side effects reported, and no new safety signals were identified.REC name
HSC REC A
REC reference
15/NI/0250
Date of REC Opinion
22 Dec 2015
REC opinion
Further Information Favourable Opinion