GREAT-2: a trial of gremubamab compared to placebo in participants with bronchiectasis and chronic Pseudomonas aeruginosa infection
| ISRCTN | ISRCTN70034823 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN70034823 |
| EudraCT/CTIS number | 2022-003215-28 |
| IRAS number | 1005993 |
| Secondary identifying numbers | 1-023-22, IRAS 1005993, CPMS 55567 |
- Submission date
- 15/11/2022
- Registration date
- 26/05/2023
- Last edited
- 04/07/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
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 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.
Gremubamab 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.
Who can participate?
People aged 18 – 85 years with bronchiectasis in the UK and Spain
What does the study involve?
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.
The 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.
What are the possible benefits and risks of participating?
Benefits:
Participants will be monitored closely during the trial by the trial team. The tests will give the trial team information about the function of participants kidneys, liver, fitness and general wellbeing. If any of these investigations reveal any new clinically significant abnormality, the trial team will tell participants and either discuss this with their GP (with your consent) or refer them to a specialist clinic at the hospital (whichever seems most appropriate.) The trial may not immediately benefit participants, but if the results of the trial are positive this may improve how people with bronchiectasis are treated.
Risks:
Previous trials have shown that there was a low risk of allergic reactions to the gremubamab infusion. There is an extremely small risk of severe allergic reaction. The risk of having an allergic reaction will be reduced by giving the infusion slowly and giving an antihistamine before the trial drug administration starts. Participants will be monitored during all infusions of trial medication. A participant's trial medication will be stopped immediately a participant develops signs of a severe allergic reaction.
A few people in the previous trials also reported headache, indigestion and itch.
If a participant develops any reaction to the infusion the doctor looking after the participant will assess it and discuss with the participant if any treatment is required. The doctor will also decide if it is suitable for the participant to continue with their infusions.
Where is the study run from?
University of Dundee (UK)
When is the study starting and how long is it expected to run for?
November 2022 to October 2024
Who is funding the study?
European Respiratory Society (UK)
Who is the main contact?
Dr James Chalmers, j.chalmers@dundee.ac.uk
Contact information
Public
Tayside Clinical Trials Unit
TASC
Level 3, Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
| Phone | +44 (0)1382 381955 |
|---|---|
| GREAT-2-TM@dundee.ac.uk |
Principal Investigator
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
 ORCID ID |
0000-0001-5514-7868 |
|---|---|
| Phone | +44 1382 386131 |
| j.chalmers@dundee.ac.uk |
Study information
| Study design | Interventional double-blind randomized placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | 42766 GREAT-2 PIS V1 10Nov22.pdf |
| Scientific title | GRemubamab ErAdication Trial (GREAT-2) A phase 2 trial of gremubamab compared to placebo in participants with bronchiectasis and chronic Pseudomonas aeruginosa infection |
| Study acronym | GREAT-2 |
| Study objectives | Primary objective: To evaluate the efficacy of gremubamab on P. aeruginosa bacterial burden in sputum at week 12 Secondary objectives: 1. To evaluate the efficacy of gremubamab on P. aeruginosa bacterial burden in sputum 2. To determine the persistent effects of gremubamab on P. aeruginosa bacterial burden following discontinuation of treatment (week 24) 3. To determine if gremubamab can achieve eradication of P. aeruginosa in some individuals 4. To determine the effect of gremubamab on health related quality of life 5. To determine the effect of gremubamab on time to first exacerbation 6. To determine the effect of gremubamab on pulmonary function 7. To assess the safety of gremubamab in patients with bronchiectasis 8. To evaluate the PK of gremubamab |
| Ethics approval(s) | Approved 11/05/2023, East of Scotland Research Ethics Service (EoSRES, Tayside Medical Science Centre, Residency Block, Level 3, George Pirie Way, Dundee, DD1 9SY, UK; +44 (0)1382 383871; tay.eosres@nhs.scot), ref: 22/ES/0051 |
| Health condition(s) or problem(s) studied | Bronchiectasis |
| Intervention | Participants will be randomised using a GCP-compliant Interactive Web-based Randomisation System to one of three treatment arms. Randomisation will be stratified by inhaled antibiotic use. Depending on randomisation participants will receive either gremubamab 1500 mg per dose, gremubamab 500 mg per dose or placebo. Participants will receive trial treatment via intravenous infusion every 4 weeks a total of three times. Participants will be assessed during the treatment period (3 months) and for a 3-month period following completion of trial treatment. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Gremubamab |
| Primary outcome measure | Efficacy of gremubamab on P. aeruginosa bacterial burden in sputum measured by change from baseline (day 1 - day 84) in quantitative sputum cultures (colony-forming unit (CFU)) |
| Secondary outcome measures | 1. Efficacy of gremubamab on P. aeruginosa bacterial burden in sputum measured by change from baseline to Days 7, 14, 28 and 56 in Quantitative sputum cultures 2. Persistent effects of gremubamab on P. aeruginosa bacterial burden following discontinuation of treatment measured by change from baseline to Day 168 in quantitative sputum cultures 3. Eradication defined by negative sputum cultures for P. aeruginosa at the end of treatment (Days 84 and 168) 4. Eradication of P. aeruginosa of measured by change from baseline to Days 28, 56, 84 and 168 in QOL-B, BIM questionnaire 5. Effect of gremubamab on health-related quality of life 5.1. Measured by change from baseline to Days 84 and 168 in St. George’s Respiratory Questionnaire 5.2. Measured by change from baseline to Days 28, 56, 84 and 168 in change from baseline in Quality of Life Bronchiectasis questionnaire 5.3. Measured by change from baseline to Days 28, 56, 84 and 168 in change from baseline in Bronchiectasis Impact Measure questionnaire 6. Effect of gremubamab on time to first exacerbation measured by occurrence of exacerbations (as per EMBARC definition of exacerbation). First event from visit 1 to day 84. 7. Effect of gremubamab on pulmonary function measured by change from baseline to Day 28, 56 and 84 in forced expiratory volume in 1 second (FEV1) 8. Safety of gremubamab in patients with bronchiectasis measured by frequency of adverse events and serious adverse events between groups over 168 days 9. Safety of gremubamab in patients with bronchiectasis measured by safety lab parameters between groups over 168 days 10. Pharmacokinetics of gremubamab measured by gremubumab PK parameters through 168 days post-dose |
| Overall study start date | 11/11/2022 |
| Completion date | 31/10/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 86 Years |
| Sex | Both |
| Target number of participants | 60 |
| Total final enrolment | 62 |
| Key inclusion criteria | 1. Age 18 ≤ 86 years 2. Clinical diagnosis of bronchiectasis. 3. Able to and provided informed consent. 4. Previous CT scan of the chest demonstrating bronchiectasis in 1 or more lobes 5. P. aeruginosa in sputum, bronchoalveolar lavage or another airway sample at least once in the 24 months prior to screening. 6. A sputum sample that is culture positive for P. aeruginosa sent at the screening visit and within 35 days of randomization. |
| Key exclusion criteria | 1. Known hypersensitivity to gremubamab or any excipient of the investigational product 2. Known clinical diagnosis of cystic fibrosis 3. Immunodeficiency requiring replacement immunoglobulin. 4. Active tuberculosis or nontuberculous mycobacterial infection (currently under treatment, or requiring treatment in the opinion of the investigator). 5. Active allergic bronchopulmonary aspergillosis (receiving treatment with corticosteroids and/or antifungal medication). 6. Recent significant haemoptysis (a volume requiring clinical intervention, within the previous 4 weeks prior to screening). 7. Treatment with long-term inhaled, systemic or nebulized anti-pseudomonal antibiotics which are newly initiated within the previous 3 months prior to screening. 8. Chronic treatment with cyclical doses of inhaled or nebulized antibiotics e.g. 28 days on and 28 days off at the time of screening. 9. Receipt of antipseudomonal antibiotics for an exacerbation during the screening period. 10. Treatment with immunosuppressives within previous 6 months prior to screening. 11. Participants with a primary diagnosis of COPD associated with >10 pack years smoking history. 12. Participants with a primary diagnosis of asthma or asthma which is considered to be poorly controlled at screening. 13. Participants with FEV1 <25% predicted value at screening. 14. Glomerular filtration rate (eGFR) below 25 ml/min/1.73m² or requiring dialysis. This will be determined at screening. 15. Use of any investigational drugs within five times of the elimination half-life after the last dose or within 30 days, whichever is longer. 16. Unstable co-morbidities (e.g. cardiovascular disease, active malignancy) which in the opinion of the investigator would make participation in the trial not in the participant’s best interest. 17. Pregnant or lactating females. 18. Women of child baring age or male partners of women of childbearing age and not practicing a method of acceptable birth control |
| Date of first enrolment | 10/08/2023 |
| Date of final enrolment | 24/01/2024 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- Spain
- United Kingdom
- Wales
Study participating centres
Ninewells Avenue
Dundee
DD1 9SY
United Kingdom
Edgbaston
Birmingham
B15 2GW
United Kingdom
Llandough
Penarth
CF64 2XX
United Kingdom
London
SW3 6NP
United Kingdom
Cambridge Biomedical Campus
Cambridge
CB2 0AY
United Kingdom
Hammersmith
London
W12 0HS
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Harlow
CM20 1QX
United Kingdom
Belfast
BT9 7AB
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
Old Dalkeith Road
Edinburgh
Lothian
EH16 4SA
United Kingdom
Harrow
HA1 3UJ
United Kingdom
Sponsor information
University/education
Ninewells Hospital and Medical School
Dundee
DD1 9SY
Scotland
United Kingdom
| Phone | +44 1382 383642 |
|---|---|
| TASCgovernance@dundee.ac.uk | |
| Website | http://www.dundee.ac.uk/ |
"ROR" |
https://ror.org/03h2bxq36 |
Funders
Funder type
Research organisation
Private sector organisation / Associations and societies (private and public)
- Alternative name(s)
- ERS
- Location
- Switzerland
Results and Publications
| Intention to publish date | 31/10/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Peer reviewed scientific journals Conference presentation Submission to regulatory authorities Consent will be sought for data to be shared for the purposes of research. Any information which identifies the participant will be removed prior to sharing. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to commercial sensitivity. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1 | 10/11/2022 | 17/11/2022 | No | Yes |
| Participant information sheet | version 2 | 05/05/2023 | 26/05/2023 | No | Yes |
| HRA research summary | 20/09/2023 | No | No | ||
| Protocol file | version 4 | 19/10/2023 | 06/12/2023 | No | No |
| Other files | version 3 | 29/09/2023 | 26/01/2024 | No | Yes |
| Participant information sheet | version 3 | 29/09/2023 | 26/01/2024 | No | Yes |
| Participant information sheet | version 2 | 05/05/2023 | 26/01/2024 | No | Yes |
| Protocol file | version 5 | 13/12/2023 | 26/01/2024 | No | No |
| Basic results | 24/06/2025 | 04/07/2025 | No | No |
Additional files
- 42766 GREAT-2 PIS V1 10Nov22.pdf
- 42766 GREAT-2 PIS V2 05May23.pdf
- ISRCTN70034823_PROTOCOL_V4_19Oct23.pdf
- ISRCTN70034823_PROTOCOL_V5_13Dec23.pdf
- ISRCTN70034823_PIS_V3_29Sep23.pdf
- ISRCTN70034823_InformedConsentForm_V3_29Sep23.pdf
- ISRCTN70034823_BriefPIS_V2_05May23.pdf
- ISRCTN70034823_BasicResults_24Jun2025.pdf
Editorial Notes
04/07/2025: The basic results have been uploaded as an additional file.
26/01/2024: The following changes were made to the study record:
1. Protocol, participant information sheet and informed consent form added.
2. The recruitment start date was changed from 14/06/2023 to 10/08/2023.
3. The recruitment end date was changed from 31/12/2023 to 24/01/2024.
4. Total final enrolment added.
06/12/2023: The following changes were made to the study record:
1. Study protocol uploaded.
2. Study website added.
3. Contact details updated.
4. The target number of participants was changed from 90 to 60.
5. The study participating centres were updated to remove Walsgrave General Hospital, Torbay Hospital, and Altnagelvin Area Hospital and add Northwick Park Hospital.
20/09/2023: A link to the HRA research summary was added.
17/08/2023: Queen Elizabeth Hospital, University Hospital Llandough, Walsgrave General Hospital, Royal Brompton Hospital, Royal Papworth Hospital, Hammersmith Hospital, Royal Devon and Exeter Hospital, Princess Alexandra Hospital, Belfast City Hospital, Wythenshawe Hospital, Royal Infirmary of Edinburgh, Torbay Hospital, and Altnagelvin Area Hospital were added to the study participating centres.
16/08/2023: England, Northern Ireland and Wales were added to the countries of recruitment.
05/06/2023: Internal review.
15/11/2022: Trial's existence confirmed by NHS HRA.
