GRemubamab ErAdication Trial (GREAT-2)

2022-502494-41-00 Protocol 1-023-22 Therapeutic exploratory (Phase II) Ended

Start 21 Nov 2023 · End 10 Jul 2024 · Status Ended · 1 EU/EEA countries · 10 sites · Protocol 1-023-22

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ended
Participants planned 90
Countries 1
Sites 10

bronchiectasis and chronic Pseudomonas aeruginosa infection

To evaluate the efficacy of Gremubamab on P. aeruginosa bacterial burden in sputum at week 12

Key facts

Sponsor
NHS Tayside, University Of Dundee
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Respiratory Tract Diseases [C08]
Trial duration
21 Nov 2023 → 10 Jul 2024
Decision date (initial)
2023-09-19
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
AstraZeneca · European Respiratory Society

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the efficacy of Gremubamab on P. aeruginosa bacterial burden in sputum at week 12

Secondary objectives 8

  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

Conditions and MedDRA coding

bronchiectasis and chronic Pseudomonas aeruginosa infection

VersionLevelCodeTermSystem organ class
23.0 LLT 10083611 Non-cystic fibrosis bronchiectasis 10038738
20.0 LLT 10045053 Tuberculous bronchiectasis tubercle bacilli found (in sputum) by microscopy 10021881

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Double blind
Parallel group design. Randomised, placebo-controlled trial.
 Randomised Controlled Double [{"id":72962,"code":2,"name":"Investigator"},{"id":72963,"code":1,"name":"Subject"}] Arm 1: 1500 mg intravenous infusion (reconstituted and diluted to a total volume of 250 mL). Intravenous infusion of 30 mL (as supplied, and diluted to a total volume of 250 mL)
Arm 2: 500 mg intravenous infusion (reconstituted and diluted to a total volume of 250 mL). Intravenous infusion of 30 mL (as supplied, and diluted to a total volume of 250 mL)
Arm 3: Placebo, liquid buffer in saline. Sterile, colourless to slightly yellow, clear to slightly opalescent liquid, free from visible particles, in a 20 mm 10R glass vial at a nominal fill volume of 4 mL, stoppered with a siliconized 20 mm chlorobutyl rubber stopper, and sealed with a flip-off cap overseal,. and is further diluted into 0.9% (w/v) saline to a total volume of 250 mL for IV infusion.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Age >18 to <86
  2. Clinical diagnosis of Bronchiectasis.
  3. Able to and provided informed consent.
  4. Previous computerised tomography (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 or PCR positive for P. aeruginosa sent at the screening visit and within 35 days of randomization

Exclusion criteria 18

  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 Chronic obstructive pulmonary disease (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 25ml/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 child baring age and not practicing a method of acceptable birth control

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Day 84

Secondary endpoints 8

  1. From Baseline to; Days 7, 14, 28 and 56
  2. From Baseline to; Day 168
  3. From Baseline to; Days 84 and 168
  4. From Baseline to; Days 28, 56, 84 and 168
  5. From Baseline to; First event from visit 1 to day 84
  6. From Baseline to; Day 28, 56 and 84
  7. From Baseline to; Over 168 days
  8. From Baseline to; Over 168 days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Gremubamab

PRD10287271 · Product

Active substance
Gremubamab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
1500 mg milligram(s)
Max total dose
4500 mg milligram(s)
Max treatment duration
12 Week(s)
Authorisation status
Not Authorised
MA holder
UNIVERSITY OF DUNDEE
Paediatric formulation
No
Orphan designation
No

Gremubamab

PRD10287678 · Product

Active substance
Gremubamab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
1500 mg milligram(s)
Max total dose
4500 mg milligram(s)
Max treatment duration
12 Week(s)
Authorisation status
Not Authorised
MA holder
NHS TAYSIDE
Paediatric formulation
No
Orphan designation
No

Gremubamab

PRD10287670 · Product

Active substance
Gremubamab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
1500 mg milligram(s)
Max total dose
4500 mg milligram(s)
Max treatment duration
12 Week(s)
Authorisation status
Not Authorised
MA holder
UNIVERSITY OF DUNDEE
Paediatric formulation
No
Orphan designation
No

Gremubamab

PRD10287281 · Product

Active substance
Gremubamab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
1500 mg milligram(s)
Max total dose
4500 mg milligram(s)
Max treatment duration
12 Week(s)
Authorisation status
Not Authorised
MA holder
NHS TAYSIDE
Paediatric formulation
No
Orphan designation
No

Placebo 1

MEDI3902 Pbo 4mL 10R

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
Route of administration
INTRAMUSCULAR OR INTRAVENOUS
Max daily dose
1500 mg milligram(s)
Max total dose
4500 mg milligram(s)
Max treatment duration
12 Week(s)
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NHS Tayside

Sponsor organisation
NHS Tayside
Address
P. O. Box 120
City
Dundee
Postcode
DD1 9SY
Country
United Kingdom

Scientific contact point

Organisation
NHS Tayside
Contact name
Chief Investigator

Public contact point

Organisation
NHS Tayside
Contact name
Clinical Trial Manager

University Of Dundee

Sponsor organisation
University Of Dundee
Address
Ninewells Avenue
City
Dundee
Postcode
DD1 9SY
Country
United Kingdom

Scientific contact point

Organisation
University Of Dundee
Contact name
Chief Investigator

Public contact point

Organisation
University Of Dundee
Contact name
Clinical Trial Manager

Sponsor responsibilities

Article 77 compliance
NHS Tayside
Contact point sponsor
NHS Tayside
Article 77 implementation
NHS Tayside

Locations

1 EU/EEA country · 10 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Ended 30 10
Rest of world
United Kingdom
 — 60 —

Investigational sites

Spain

10 sites · Ended
Ajuntament De L Hospitalet De Llobregat
Respiratory, Calle D Amadeu Torner 63, 08902, L Hospitalet De Llobregat
Hospital Universitari De Girona Doctor Josep Trueta
Pneumology, Avinguda De Franca S/n, 17007, Girona
Hospital Clinic De Barcelona
Respiratory, Calle De Sabino Arana 1, 08028, Barcelona
Hospital Universitario Ramon Y Cajal
Respiratory, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
Hospital Universitario Y Politecnico La Fe
Pneumology, Avenida De Fernando Abril Martorell 106, 46026, Valencia
University Hospital Son Espases
Respiratory Medicine, Carretera Valldemossa 79, 07120, Palma
Hospital Del Mar
Pulmonology, Passeig Maritim De La Barceloneta 25-29, 08003, Barcelona
Hospital Universitari Germans Trias I Pujol
Respiratory, Ctra. Canyet S/n, Edificio General 1a Planta, Badalona
Hospital Universitari Vall D Hebron
Respiratory, Passeig De La Vall D Hebron 119-129, 08035, Barcelona
Hospital De La Santa Creu I Sant Pau
Respiratory, Calle De San Antonio Maria Claret 167, 08025, Barcelona

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2023-11-21 2023-11-21 2024-01-24

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
GREAT-2 Results 24-06-25
SUM-95648
 2025-08-28T10:28:24 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
GREAT-2 Participant Results Summary Sheet V1 23-07-25 Spain 2025-08-28T10:29:02 Submitted Laypersons Summary of Results

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Laypersons summary of results (for publication) GREAT-2 Participant Results Summary Sheet V1 23-07-25 Spain 1
Protocol (for publication) GREAT-2 Protocol Spain V2 06-10-23 2
Protocol (for publication) GREAT-2 Protocol Spain V2 06-10-23 TRACK CHANGES 2
Summary of Product Characteristics (SmPC) (for publication) MEDI3902 No SmPC 1
Summary of results (for publication) GREAT-2 Results 24-06-25 1
Synopsis of the protocol (for publication) GREAT-2 Protocol Synopsis - Spanish 1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-05-30 Spain Acceptable
2023-09-18
 2023-09-19
2 SUBSTANTIAL MODIFICATION SM-1 2023-10-13 Spain Acceptable
2023-11-27
 2024-01-15
3 SUBSTANTIAL MODIFICATION SM-3 2024-07-25 Spain Acceptable
2024-08-12
 2024-08-12