GRemubamab ErAdication Trial (GREAT-2)
Research type
Research Study
Full title
GRemubamab ErAdication Trial (GREAT-2) A phase 2 trial of Gremubamab compared to placebo in participants with bronchiectasis and chronic Pseudomonas aeruginosa infection
IRAS ID
1005993
Contact name
James Chalmers
Contact email
Sponsor organisation
University of Dundee
Eudract number
2022-003215-28
ISRCTN Number
ISRCTN70034823
Research summary
Research Summary
Patients with bronchiectasis often get chest infections which are difficult to treat causing coughing, sputum (phlegm) production, breathlessness and tiredness. Approximately one third of people with bronchiectasis become infected with a bacteria called Pseudomonas aeruginosa (P. aeruginosa). P. aeruginosa can often become resistant to antibiotics. The purpose of this trial is to test whether an intravenous infusion (drip) containing a new drug called Gremubamab can reduce the amount of infection with P. aeruginosa.
The purpose of this trial is to test whether a new drug called Gremubamab, given intravenously, can reduce the amount of infection with P. aeruginosa in people with bronchiectasis. Whether Gremubamab can help reduce the number of bronchiectasis exacerbations and improves quality of life will also be examined. The safety of Gremubamab use in people with bronchiectasis will be assessed.
Gremubanab is a type of drug called a monoclonal antibody which is expected to work with the immune system to eliminate the P. aeruginosa infection.
Gremubamab is a new medication which is being developed by AstraZeneca. It has been used in a few trials already, in healthy people (Phase I trial) and people who were on a ventilator in intensive care and developed pneumonia (Phase II trial). Phase I trials look at the safety of new drugs and phase II trials look at how effective new drugs are as well as their safety. This trial is a phase II trial which will look at the safety and effectiveness of Gremubamab in people with bronchiectasis.
A total of 90 people in the UK and Spain will be enrolled.
The health of participants treated with Gremubamab will be compared with the health of participants given a placebo. The effects of two different doses will also be compared.
Participant will be in the trial for 6 months and will receive infusions of the gremubamab/placebo at monthly intervals for the first 3 months. The trial is expected to run for a total of 18 months.Summary of Results
The GREAT-2 trial
Bronchiectasis is the third most common airway disease. People with bronchiectasis frequently get chest infections which are difficult to treat and can cause coughing, phlegm production, breathlessness and tiredness. Approximately one third of people with bronchiectasis become infected with a bacteria called Pseudomonas aeruginosa (P. aeruginosa). This infection often becomes resistant to antibiotics which means antibiotics don’t work. People are often left with a chronic infection which is difficult to treat.
Finding new treatments to treat this infection is important. The purpose of the GREAT-2 trial was to test whether an intravenous infusion (drip) containing a new drug called Gremubamab could reduce the amount of infection with P. aeruginosa.
How does this drug work?
Gremubamab is a new medication (called an antibody) which has been developed by AstraZeneca. An antibody is a protein used by the immune system of the body to identify bacteria and viruses that cause disease. Gremubamab is an antibody designed to work with the immune system to eliminate the P. aeruginosa infection.
Who took part in the GREAT-2 trial?
GREAT-2 was a randomised controlled trial, which included people diagnosed with bronchiectasis with P. aeruginosa in their sputum. The trial took place in 12 hospitals in the UK and 6 hospitals in Spain.
62 people attended a screening visit and 37 people were able to take part and joined the trial. Participants took part in the trial over 6 months and they were given 3 infusions of either Gremubamab 1500mg, Gremubamab 500mg or a placebo (dummy).
12 people received Gremubamab 1500mg
13 people received Gremubamab 500mg
12 people received the placebo
What were the main results of the GREAT-2 trial?
Gremubamab was shown to be safe, with similar side effects reported by people who received Gremubamab & people who received the placebo.
Compared with people who received the placebo, people who received Gremubamab had:
Less P. aeruginosa infection in the lungs,
Less flare ups (bronchiectasis exacerbations),
Reported better quality of life.
What happens now?
Professor James Chalmers, who was the lead clinician for the GREAT-2 trial, said:
“When you see this kind of improvement in quality of life and reduced chest infections it is very encouraging. The symptom improvements we have seen in patients in the trial are greater than anything we’ve seen before with antibiotic treatments. If this can be replicated in larger trials, this could be a major step forward in developing treatments for antibiotic resistant Pseudomonas infections and bronchiectasis.”
Researchers will use these results to continue to develop treatments for antibiotic resistant Pseudomonas infections and bronchiectasis.
This trial was funded by the European Respiratory Society. Gremubamab and placebo treatments were provided by AstraZeneca.REC name
East of Scotland Research Ethics Service REC 2
REC reference
22/ES/0051
Date of REC Opinion
11 May 2023
REC opinion
Further Information Favourable Opinion