The MONACO Cell Therapy Study: Monocytes as an Anti-fibrotic Treatment After COVID-19

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I/II MONACO Cell Therapy Study: Monocytes as an Anti-fibrotic Treatment After COVID-19

Conditions
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Pulmonary Fibrosis, Interstitial Lung Disease, Covid19

Intervention / Treatment
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* Biological: MON002


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MON002<br>Minimum of 1x10 7 cells to maximum of 2x10 6 cells/kg. Single infusion. | Biological: MON002<br>* Autologous monocytes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of serious adverse events (SAE) related to the administration of the IMP | 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 | Total number of SAEs at 12 months after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 3, 6 and 12 months | 
| 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 | Score is transformed to range from 0-100. 100=best health status | 3, 6 and 12 months | 
| Improvement in quality of life as indicated by the 36-Item Short Form Survey (SF-36) score | Score is transformed to range from 0-100. 100=best health status | 3, 6 and 12 months | 
| Reduction in fibrosis score on high resolution lung CT |  | 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I/II, cell therapy, ATIMP