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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Covid19; Pulmonary Fibrosis; Interstitial Lung Disease
• Intervention / Treatment: Biological: MON002

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 Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ashish Patel, PhD FRCS; Phone Number: +442071880214; Email: ashish.patel@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's & St Thomas' NHS Foundation Trust
    • Contact: Ashish Patel, PhD FRCS; Phone Number: +442071880214; Email: ashish.patel@kcl.ac.uk
    • Contact: Bijan Modarai, PhD FRCS; Phone Number: +442071880214; Email: bijan.modarai@kcl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical evidence/diagnosis of interstitial lung disease (fibrosis) following COVID-19 infection
2. Aged at least 18 years
3. Willing and able to participate in the MONACO Cell Therapy Study
4. Signed and dated written informed consent.

Exclusion Criteria:

1. Subjects who have had other investigational medicinal products within 90 days prior to screening or during the treatment phase.
2. Malignant or premalignant haematological conditions
3. Serologically positive for antiHIV1,2; HBsAg; Anti-HBc; Anti-HCVab;Anti-HTLV1,2 or syphilis (Treponema palladium)
4. 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)
5. Evidence of significant local or systemic infection
6. Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
7. Clinical diagnosis of interstitial lung disease prior to the COVID-19 infection
8. Any condition which, in the judgement of the Investigator, would place the subject at undue risk
9. Female patients of childbearing potential with a positive serum pregnancy test at enrolment
10. 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
11. Female patients who are breastfeeding
12. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow up visit schedule
13. 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
14. Patients unable to freely give their informed consent (e.g. individuals under legal guardianship).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MON002; Minimum of 1x10~7 cells to maximum of 2x10~6 cells/kg. Single infusion.	Biological: MON002; Autologous monocytes

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: 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 record dates

Study Major Dates

• Study Start (ANTICIPATED): March 8, 2021
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): March 5, 2023

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 17, 2021
• First Posted (ACTUAL): March 18, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: cell therapy; Phase I/II; ATIMP
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; COVID-19; Lung Diseases; Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: 289624

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No