A Phase 2 safety and efficacy study of Lenabasum in Cystic Fibrosis
Research type
Research Study
Full title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic Fibrosis
IRAS ID
242168
Contact name
Damian Downey
Contact email
Sponsor organisation
Corbus Pharmaceuticals, Inc.
Eudract number
2017-003723-29
Clinicaltrials.gov Identifier
126359, Investigational New Drug Number
Duration of Study in the UK
1 years, 8 months, 6 days
Research summary
Research Summary
Cystic Fibrosis (CF) is an inherited condition that affects multiple organs, including the lungs, pancreas, liver and intestine. Most cases of CF in the UK are now identified through screening tests carried out soon after birth. It's estimated that 1 in every 2,500 babies born in the UK has CF. Symptoms of CF tend to start in early childhood, although they can sometimes develop very soon after birth, or may not be obvious until adulthood. Some of the main symptoms of CF can include: recurring chest infections, difficulty putting on weight, frequent and wet sounding coughs, diarrhoea, and wheezing or shortness of breath. Chest infections develop due to increased mucus production and often require treatment with antibiotics. Episodes of acute worsening of cough and sputum production are called Pulmonary Exacerbations (PEx). The target population for this trial will have an increased risk of suffering from a Pulmonary Exacerbation (PEx) in the next 6 months.Lenabasum is an investigational drug that is expected to reduce the lung inflammation that occurs following events such as viral or bacterial infection, thus reducing the need for antibiotics, reduce hospitalizations, increase quality of life and reduce long term damage to the lungs caused by inflammation. This study will look at the efficacy and safety of Lenabasum.
A total of 415 male and female patients 12 years old and older will be will be randomly assigned into 1 of 3 cohorts in a 2:1:2 ratio: 20mg twice a day, 5mg twice a day or placebo twice a day for 28 weeks. The study drug is taken orally. There is a screening period (up to 4 weeks) followed by a treatment period consisting of 8 visits over 28 weeks. The final visit will be a follow up visit 32 weeks after start of study treatment. Patients who suffer from a PEx will attend extra visits if required. Subjects who receive at least one dose of study drug are considered enrolled in the study.
Study procedures include vital signs, height, weight, collection of blood and sputum samples, physical examination, spirometry, ECG and questionnaires.
The study sponsor is Corbus Pharmaceuticals, Inc.
Summary of Results
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial to Evaluate Efficacy and Safety of Lenabasum in Cystic FibrosisResearchers look at the results of many studies to understand which drugs work and how they work. It takes many people in many studies all around the world to advance medical science. This summary includes the results of only this one study. Other studies may find different 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 (151)
• Canada (14)
• Serbia (6)
• Russian Federation (30)
• Romania (1)
• Slovakia (8)
• Netherlands (1)
• Poland (39)
• Portugal (4)
• Spain (12)
• Sweden (9)
• United Kingdom (35)
• Austria (7)
• Belgium (4)
• Bulgaria (9)
• Czechia (4)
• France (29)
• Germany (27)
• Greece (4)
• Hungary (35)
• Italy (18)
When did the study take place?
The study started in 08 May 2018 and ended in 17 June 2020.
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 being tested (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. The study drug and placebo taken in this study were provided as identical capsules to be swallowed.
General information about the disease cystic fibrosis 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, 425 men and women with CF aged 12 to 65 years were treated during the study. People with severe or unstable CF were not allowed to take part. In total, 254 people took either 5 mg lenabasum (89 people) or 20 mg lenabasum (165 people), and 171 people took a placebo.
The analysis compared all 254 patients treated with lenabasum to 171 patients treated with placebo.
How long were patients in the study?
The patients were treated for 28 weeks.
The time on study treatment was similar between people on lenabasum 20 mg twice daily (185.7 days), lenabasum 5 mg twice daily (194.5 days), and placebo (188.4 days).
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?
List 1: Serious side effects:
Serious side effects related to the study treatment were as listed below.
Lenabasum (20 mg):
• Infective pulmonary exacerbation of cystic fibrosis (worsening lung symptoms of CF): 2 of 165 patients (1.2%)
• Distal intestinal obstruction syndrome (small intestine blocked by thickened stool): 1 of 165 patients (0.6%)
• Haemoptysis (cough up blood): 1 of 165 patients (0.6%)
Lenabasum (5 mg):
• Infective pulmonary exacerbation of cystic fibrosis (worsening lung symptoms of CF): 1 of 89 patients (1.1%)
There were no deaths in this study.
List 2a: Other side effects; lenabasum 20 mg:
Other side effects related to the study treatment (that were not serious), and were reported for more than 1 person on treatment, were as listed below:
• Dizziness: 11 of 165 patients (6.6%)
• Headache: 8 of 165 patients (4.8%)
• Dry mouth: 8 of 165 patients (4.8%)
• Fatigue (tiredness): 8 of 165 patients (4.8%)
• Infective pulmonary exacerbation of cystic fibrosis (worsening lung symptoms of CF): 7 of 165 patients (4.2%)
• Haemoptysis (coughing up blood from lungs): 5 of 165 patients (3.0%)
• Cognitive disorder (noticeably reduced mental ability): 3 of 165 patients (1.8%)
• Cough: 3 of 165 patients (1.8%)
• Sputum increased (increased mucus): 3 of 165 patients (1.8%)
• Confusional state (confused): 2 of 165 patients (1.2%)
• Dyspnoea (shortness of breath): 2 of 165 patients (1.2%)
• Insomnia (difficulty sleeping): 2 of 165 patients (1.2%)
• Somnolence (sleepiness): 2 of 165 patients (1.2%)
List 2b: Other side effects; lenabasum 5 mg:
Other side effects related to the study treatment (that were not serious) included:
• Headache: 4 of 89 patients (4.4%)
• Infective pulmonary exacerbation of cystic fibrosis: 3 of 89 patients (3.3%)
• Asthenia (weakness, lack of energy): 2 of 89 patients (2.3%)
• Diarrhoea: 2 of 89 patients (2.3%)
• Dizziness: 2 of 89 patients (2.3%)
• Fatigue (tiredness): 2 of 89 patients (2.2%)
• Sputum abnormal (abnormal mucus): 2 of 89 patients (2.3%)
Safety summary:
Lenabasum was safe and well tolerated in this study. There were no deaths reported, and no new safety signals were found.
Five serious side effects (See List 1 above) were considered related to study product by the investigator. They included infective pulmonary exacerbation of CF reported in 2 subjects in lenabasum 20 mg twice daily group and 1 subject in lenabasum 5 mg twice daily group, small intestine blockage with thickened stool reported in in 1 subject in the lenabasum 20 mg twice daily group, and coughing up blood from lungs reported in 1 subject in the lenabasum 20 mg twice daily group. All 5 serious treatment-related side effects were resolved by the end of study.
The incidence of side effects leading to study product discontinuation was low (6.7% of subjects in the lenabasum 20 mg twice daily group and 2.2% of subjects in the lenabasum 5 mg twice daily group). The most frequent side effect leading to discontinuation of study product was infective pulmonary exacerbation of CF in 3 subjects in the lenabasum 20 mg twice daily group and 1 in the lenabasum 5 mg twice daily group.
Lenabasum did not appear to be associated with any clinically relevant patterns of change in clinical laboratory assessments, vital signs, or ECGs for either the lenabasum 20 mg twice daily or lenabasum 5 mg twice daily groups. Clinically significant changes in physical examinations were observed in both treatment groups and were largely confined to changes in general appearance and lung examination, indicating pulmonary exacerbations.Overall results of the study
Is lenabasum effective in treatment patients with cystic fibrosis?
A total of 447 adolescents and adults with CF from the US, Canada, and Europe were enrolled into the study and 425 received lenabasum 20 mg twice daily, lenabasum 5 mg twice daily, or placebo twice daily. All people in the study had a high risk for recurrent CF lung problems.
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 28 weeks of treatment compared with people treated with placebo. In this study, the rates of CF lung problems were similar in people treated with 20 mg or 5 mg lenabasum twice daily and people treated with 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 20 mg or lenabasum 5 mg and people treated with placebo.
Lenabasum was safe and well tolerated in this study. There were no deaths reported, and no new safety signals were identified. There was no increase in serious side effects during treatment in the lenabasum.
How has this study helped patients and researchers?
Studies with lenabasum are ongoing, and further studies are planned. The effects observed in the patients in this study may be helpful in future studies of lenabasum in patients with CF.
Where can I find more information about this study?
Further information on this study can be found at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=04%7C01%7Capprovals%40hra.nhs.uk%7C3c6db4031b5b4aa1c77508d9e0e3c831%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637788091191411232%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=HUY%2B8VHg3IDX%2F9i%2B23ZYhdXM47%2FJXeJ%2BFjux2kFfC2o%3D&reserved=0 (study number 2017-003723-29) and at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=04%7C01%7Capprovals%40hra.nhs.uk%7C3c6db4031b5b4aa1c77508d9e0e3c831%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637788091191411232%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=T0%2FrUhgL1bMIvF0dIAstBw7IN1ESlGll8gPKjiXl9wc%3D&reserved=0 (study number NCT03451045).REC name
HSC REC A
REC reference
18/NI/0060
Date of REC Opinion
11 May 2018
REC opinion
Further Information Favourable Opinion