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

• ClinicalTrials.gov Identifier: NCT04805086
• Recruitment Status: Unknown
• First Posted: March 18, 2021
• Last Update Posted: March 18, 2021
• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborator: King's College London
• Information provided by (Responsible Party): Guy's and St Thomas' NHS Foundation Trust

Tracking Information

• First Submitted Date: March 3, 2021
• First Posted Date: March 18, 2021
• Last Update Posted Date: March 18, 2021
• Estimated Study Start Date: March 8, 2021
• Estimated Primary Completion Date: June 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 17, 2021)

Frequency of serious adverse events (SAE) related to the administration of the IMP [ Time Frame: 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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: March 17, 2021)

• Absolute change from baseline of predicted forced vital capacity (FVC) [ Time Frame: 3, 6 and 12 months ]
• Rate of decrease in FVC [ Time Frame: 3, 6 and 12 months ]
• Time to first occurrence of a ≥10% absolute decline in percentage of predicted FVC [ Time Frame: 3, 6 and 12 months ]
• Time to decrease from baseline (relative change) of ≥ 10% in FVC (mL/year) [ Time Frame: 3, 6 and 12 months ]
• Time from cell administration to first event of acute pulmonary fibrosis exacerbation [ Time Frame: 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). [ Time Frame: 3, 6 and 12 months ]
• Improvement in quality of life as indicated by the King's Brief Interstitial Lung Disease (K-BILD) score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 6 and 12 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• 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
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Prospective trial

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Pulmonary Fibrosis
• Interstitial Lung Disease
• Covid19

Intervention

Biological: MON002

Autologous monocytes

Study Arms

Experimental: MON002

Minimum of 1x10~7 cells to maximum of 2x10~6 cells/kg. Single infusion.

Intervention: Biological: MON002

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 17, 2021): 5
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 5, 2023
• Estimated Primary Completion Date: June 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04805086
• Other Study ID Numbers: 289624
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Guy's and St Thomas' NHS Foundation Trust
• Original Responsible Party: Same as current
• Current Study Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Original Study Sponsor: Same as current
• 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

• PRS Account: Guy's and St Thomas' NHS Foundation Trust
• Verification Date: March 2021