Clinical trial NCT04805086: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Pulmonary Fibrosis
Interstitial Lung Disease
Covid19
Keywords: Phase I/II
cell therapy
ATIMP
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: King's College London
First posted: 2021-03-18
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective trial
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Frequency of serious adverse events (SAE) related to the administration of the IMP
timeFrame: Total number of SAEs at 12 months after administration
Secondary outcomes:
measure: Absolute change from baseline of predicted forced vital capacity (FVC)
timeFrame: 3, 6 and 12 months
measure: Rate of decrease in FVC
timeFrame: 3, 6 and 12 months
measure: Time to first occurrence of a ≥10% absolute decline in percentage of predicted FVC
timeFrame: 3, 6 and 12 months
measure: Time to decrease from baseline (relative change) of ≥ 10% in FVC (mL/year)
timeFrame: 3, 6 and 12 months
measure: Time from cell administration to first event of acute pulmonary fibrosis exacerbation
timeFrame: 3, 6 and 12 months
measure: Absolute change in transfer capacity of the lung (TLCO).
timeFrame: 3, 6 and 12 months
measure: Improvement in quality of life as indicated by the King's Brief Interstitial Lung Disease (K-BILD) score
timeFrame: 3, 6 and 12 months
measure: Improvement in quality of life as indicated by the 36-Item Short Form Survey (SF-36) score
timeFrame: 3, 6 and 12 months
measure: Reduction in fibrosis score on high resolution lung CT
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust
Study officials:
affiliation: King's College London and Guy's & St Thomas' NHS Foundation Trust
name: Ashish Patel, PhD FRCS
role: STUDY_CHAIR
affiliation: King's College London and Guy's & St Thomas' NHS Foundation Trust
name: Bijan Modarai, PhD FRCS
role: PRINCIPAL_INVESTIGATOR
References: