An early-phase clinical study to provide early data on an inhibitor/blocker of an important part of the immune system in the lung
| ISRCTN | ISRCTN35867933 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN35867933 |
| IRAS number | 318427 |
| Secondary identifying numbers | AC22119, IRAS 318427 |
- Submission date
- 09/11/2022
- Registration date
- 21/12/2022
- Last edited
- 20/09/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Interstitial lung disease (ILD) is an umbrella term used for a large group of diseases that cause scarring (fibrosis) in the lungs, inflammation in the lungs, or a mixture of both. The scarring causes stiffness in the lungs which makes it difficult to breathe and get oxygen to the bloodstream.
As there are more than 100 different types of ILD, it is difficult to monitor and treat these conditions effectively. Currently, the diagnosis of conditions involving fibrosis/scarring relies on a number of different measures, including lung biopsy, and available treatments following diagnosis are often limited. New potential drugs are in development to treat fibrotic conditions but in order for them to work effectively, we need to better understand how this process works and be able to see the effects treatments are having directly in the lungs of patients.
In the lung, ILD has also been associated with higher levels of certain types of immune cells (alveolar macrophages). Normally, these immune cells are important in keeping the lungs free of pollutants and infection but in a large number of ILD cases, they can become ‘over-active’ and result in scarring. Developing treatments that target these immune cells could help to reverse or slow the rate of ILD progression.
Who can participate?
Adult patients with a diagnosis of suspected or confirmed ILD or bronchiectasis
What does the study involve?
This study involves a new compound that has been shown to dampen down the activity of these particular immune cells outside of the body. The next step is to find out if small amounts of this compound target these cells in the lung. This liquid compound will be delivered into the lung during a routine bronchoscopy procedure and small amounts of lung fluid or samples will be taken to assess if it is having an effect on the immune cells.
What are the possible benefits and risks of participating?
While there will be no direct benefit to the patient, we are testing this new compound to see if it has an effect on certain immune cells that are key to the progression of inflammation in the lung. The information we gain from this study will help us improve our understanding and treatment of inflammatory lung diseases.
Where is the study run from?
The Queen's Medical Research Institute, The University of Edinburgh (UK)
When is the study starting and how long is it expected to run for?
June 2022 to September 2024
Who is funding the study?
Adiso Therapeutics (USA)
Who is the main contact?
Dr Annya Bruce, annya.bruce@ed.ac.uk (UK)
Contact information
Scientific
Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
| Phone | +44 (0)1312429180 |
|---|---|
| annya.bruce@ed.ac.uk |
Study information
| Study design | Exploratory non-randomized phase 0 experimental medicine study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Micro: A phase 0 experimental medicine study to provide early mechanistic data in humans of NLRP3/1 inflammasome inhibition after direct intrapulmonary dosing of ADS032. |
| Study acronym | MICRO |
| Study objectives | This study seeks to test the hypotheses that a novel clinical investigational agent (CIA) can attenuate alveolar macrophage (AM) inflammasome activity. This study specifically asks the question: In treatment-naive patients with confirmed or suspected interstitial lung disease (ILD) (which includes sarcoidosis), and in patients with bronchiectasis, can this compound that is delivered to the distal lung, attenuate IL-1β secretion and other markers of inflammasome activity in AMs retrieved from bronchoalveolar lavage (BAL)? |
| Ethics approval(s) |
Approved 27/04/2023, South Central - Oxford B Research Ethics Committee (Temple Quay House, 2 The Square, Bristol, BS1 6PN, United Kingdom; +44 207 104 8241; oxfordb.rec@hra.nhs.uk), ref: 23/SC/0077 |
| Health condition(s) or problem(s) studied | Interstitial lung disease or bronchiectasis |
| Intervention | This study seeks to test the hypotheses that a novel Clinical Investigational Agent (CIA), ADS032, can attenuate alveolar macrophage inflammasome activity in the human lung. ADS032 will be microdosed into the distal lung during a bronchoscopy procedure. Up to 100 μg of ADS032 (approximately 1.5 ml) will be delivered into the distal lung using a medically approved catheter. This can be administered as single or smaller divided doses. Lung fluid samples and blood will be taken either before, during or after the procedure. Patients will be reviewed at 4 hours and their participation in the study will end at 24 hours post-procedure. Group 1: Patients with suspected or confirmed Interstitial lung disease (ILD) or bronchiectasis will receive a microdose of the inflammasome inhibitor ADS032. Patients will also receive the equivalent regime of saline to enable them to act as their own control when samples are compared. Group 2: Patients undergoing surgical resection of the lung will receive a microdose of ADS032. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic |
| Phase | Phase 0 |
| Drug / device / biological / vaccine name(s) | ADS032 |
| Primary outcome measure | To evaluate early mechanistic data following administration of ADS032 assessed by measuring key inflammatory cytokine levels in the lung fluid of suspected or confirmed ILD patient groups measured using a variety of laboratory techniques, for example, ELISA at a single time point post the bronchoscopy |
| Secondary outcome measures | 1. Key exploratory biomarkers and their response will be evaluated (e.g. cytokines, chemokines, cell surface markers) will be measured using a variety of laboratory techniques immediately before the procedure and following the administration of ADS032 at a single time point post bronchoscopy 2. Pharmacokinetics parameters (e.g. quantification) of ADS0132 in blood and urine measured using standard laboratory techniques immediately before the procedure and 4 hours post procedure |
| Overall study start date | 01/06/2022 |
| Completion date | 01/09/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Up to 20 |
| Key inclusion criteria | 1. Provision of informed consent 2. Aged at least 18 years old and over 3. Diagnosis of suspected or confirmed ILD or bronchiectasis (Group 1) and ability to have a bronchoscopy 4. Patient undergoing surgical resection of lung for a suspected inflammatory, fibrotic or malignant process (Group 2) 5. Is not participating in a Clinical Trial of an Investigational Medicinal Product (CTIMP) |
| Key exclusion criteria | 1. Pregnant or breastfeeding 2. Known hypersensitivity to ADS032 3. In the Investigator’s opinion, the patient is unwilling or unable to undergo a bronchoscopy, laboratory tests or other study procedures 4. ILD and bronchiectasis patients receiving steroids or other immunomodulators (defined as any drugs that may suppress the immune system - azathioprine, mycophenolate, ongoing chemotherapy, macrolide antibiotics) 5. Already participated in Group 1 of this study |
| Date of first enrolment | 15/09/2023 |
| Date of final enrolment | 01/06/2024 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
Old Dalkeith Road
Edinburgh
Lothian
EH16 4SA
United Kingdom
Sponsor information
University/education
University of Edinburgh and NHS Lothian
Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)1312429180 |
|---|---|
| researchgovernance@ed.ac.uk | |
| Website | https://www.accord.scot/ |
"ROR" |
https://ror.org/01x6s1m65 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 20/09/2023 | No | No |
Editorial Notes
20/09/2023: A link to the HRA research summary was added.
30/08/2023: The following changes were made to the trial record:
1. The scientific title was changed from "A phase 0 experimental medicine study to provide early mechanistic data in humans on an inflammasome inhibitor in the lung (MICRO)" to "Micro: A phase 0 experimental medicine study to provide early mechanistic data in humans of NLRP3/1 inflammasome inhibition after direct intrapulmonary dosing of ADS032.".
2. The IRAS number was added.
3. The ethics approval was added.
4. The pharmaceutical study types were added.
5. The phase was added.
6. The study website was added.
7. The recruitment start date was changed from 15/06/2023 to 15/09/2023.
05/04/2023: The following changes have been made and the plain English summary updated accordingly:
1. The overall trial start date has been changed from 01/09/2022 to 01/06/2022.
2. The recruitment start date has been changed from 01/04/2023 to 15/06/2023.
3. The recruitment end date has been changed from 01/11/2023 to 01/06/2024.
4. The overall trial end date has been changed from 31/12/2023 to 01/09/2024.
5. The intention to publish date has been changed from 01/02/2024 to 01/12/2024.
25/11/2022: Trial's existence confirmed by the University of Edinburgh and Lothian Health Board (UK).
