The MONACO Cell Therapy Study: Monocytes as an Anti-fibrotic Treatment After COVID-19
Study Details
Study Description
Brief Summary
Up to a third of patients who recovered from SARS coronavirus (SARS-CoV) had a 20% decline in lung function with a long term reduction in exercise capacity and SF-36 health status a year after infection. Similar outcomes are now being reported in COVID-19 patients, with interstitial lung disease (fibrosis) and long term lung function decline being a common feature. Anti-fibrotic monocytes/macrophages are important for the clearance of partially degraded collagen fragments of fibrotic extracellular matrix, in particular fibrillary-type collagen.
MON002 is an autologous monocyte product, cultured in vitro prior to intravenous delivery into patients with post-COVID-19 lung fibrosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The MONACO Cell Therapy Study is a prospective, non-randomised, open label study phase I/II clinical trial with a key objective of evaluating safety of MON002 in 5 adults who have a clinical diagnosis of interstitial lung disease (pulmonary fibrosis) after recovery from acute COVID-19 infection. The main objectives of this study are to: (1) to determine the safety profile of MON002 by assessing clinical responses in adults with post-COVID-19 pulmonary fibrosis and (2) to assess its impact on reducing disease morbidity/severity in this population.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MON002 Minimum of 1x10~7 cells to maximum of 2x10~6 cells/kg. Single infusion. |
Biological: MON002
Autologous monocytes
|
Outcome Measures
Primary Outcome Measures
- Frequency of serious adverse events (SAE) related to the administration of the IMP [Total number of SAEs at 12 months after administration]
Any SAEs that result in death, are life-threatening, require hospitalisation or prolonged or existing hospitalisation (that are not determined to be as a result of disease progression) or result in persistent or significant disability or incapacity
Secondary Outcome Measures
- Absolute change from baseline of predicted forced vital capacity (FVC) [3, 6 and 12 months]
- Rate of decrease in FVC [3, 6 and 12 months]
- Time to first occurrence of a ≥10% absolute decline in percentage of predicted FVC [3, 6 and 12 months]
- Time to decrease from baseline (relative change) of ≥ 10% in FVC (mL/year) [3, 6 and 12 months]
- Time from cell administration to first event of acute pulmonary fibrosis exacerbation [3, 6 and 12 months]
Defined by (a) worsening or development of dyspnoea and radiologic evidence of new bilateral ground-glass abnormality or consolidation superimposed on a reticular or honeycomb background pattern
- Absolute change in transfer capacity of the lung (TLCO). [3, 6 and 12 months]
- Improvement in quality of life as indicated by the King's Brief Interstitial Lung Disease (K-BILD) score [3, 6 and 12 months]
Score is transformed to range from 0-100. 100=best health status
- Improvement in quality of life as indicated by the 36-Item Short Form Survey (SF-36) score [3, 6 and 12 months]
Score is transformed to range from 0-100. 100=best health status
- Reduction in fibrosis score on high resolution lung CT [6 and 12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinical evidence/diagnosis of interstitial lung disease (fibrosis) following COVID-19 infection
-
Aged at least 18 years
-
Willing and able to participate in the MONACO Cell Therapy Study
-
Signed and dated written informed consent.
Exclusion Criteria:
-
Subjects who have had other investigational medicinal products within 90 days prior to screening or during the treatment phase.
-
Malignant or premalignant haematological conditions
-
Serologically positive for antiHIV1,2; HBsAg; Anti-HBc; Anti-HCVab;Anti-HTLV1,2 or syphilis (Treponema palladium)
-
Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully treated non metastatic basal/squamous cell carcinoma of the skin)
-
Evidence of significant local or systemic infection
-
Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
-
Clinical diagnosis of interstitial lung disease prior to the COVID-19 infection
-
Any condition which, in the judgement of the Investigator, would place the subject at undue risk
-
Female patients of childbearing potential with a positive serum pregnancy test at enrolment
-
Sexually active Women of Childbearing Potential who do not agree continued abstinence from heterosexual intercourse or to use highly effective methods of birth control for the duration up to 4 weeks post IMP administration. Men who do not agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy after receiving the therapy
-
Female patients who are breastfeeding
-
Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow up visit schedule
-
Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel
-
Patients unable to freely give their informed consent (e.g. individuals under legal guardianship).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Guy's & St Thomas' NHS Foundation Trust | London | United Kingdom | SE1 7EH |
Sponsors and Collaborators
- Guy's and St Thomas' NHS Foundation Trust
- King's College London
Investigators
- Study Chair: Ashish Patel, PhD FRCS, King's College London and Guy's & St Thomas' NHS Foundation Trust
- Principal Investigator: Bijan Modarai, PhD FRCS, King's College London and Guy's & St Thomas' NHS Foundation Trust
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 289624