Inflammatory Signal Inhibitors for COVID-19 (MATIS)

NCT04581954 | Completed Phase 1 DMC

• 2 other identifiers: 20HH59262020-001750-22
• Study Type: interventional
• Target: 185
• Locations: 1 country
• Sites: 5

Brief Summary

The Multi-arm trial of Inflammatory Signal Inhibitors for COVID-19 (MATIS) study is a two-stage, open-label, randomised controlled trial assessing the efficacy of ruxolitinib (RUX) and fostamatinib (FOS) individually, compared to standard of care in the treatment of COVID-19 pneumonia. The primary outcome is the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Patients are treated for 14 days and will receive follow-up assessment at 7, 14 and 28 days after the first study dose. Patients with mild or moderate COVID-19 pneumonia will be recruited. Initially, n=171 (57 per arm) patients will be recruited in Stage 1. Following interim analysis to assess the efficacy and safety of the treatments, approximately n=285 (95 per arm) will be recruited during Stage 2.

Conditions

Coronavirus; Covid19; Pneumonia

Keywords

coronavirus; covid19; pneumonia; ruxolitinib; fostamatinib

Outcome Measures

Primary Outcomes (1)

• Progression from mild to severe COVID-19 pneumonia within 14 days in hospitalised patients

  Patients are recruited at a WHO COVID-19 Severity Score of 3 and 4 and the primary endpoint is the comparison of patients whose COVID-19 pneumonia progresses to a severity score ≥ 5 on the modified WHO Ordinal Scale. Specifically, the primary endpoint is met when the following are recorded within 14 days: * Death * Requirement for invasive ventilation * Requirement for non-invasive ventilation including CPAP or high flow nasal oxygen * O2 saturation \< 90% on ≥60% inspired oxygen

  Day 14

Secondary Outcomes (26)

• Mortality

  Day 14

• Mortality

  Day 28

• Invasive ventilation

  Day 14

• Invasive ventilation

  Day 28

• Non-invasive ventilation including CPAP and high flow nasal oxygen

  Day 14

Study Arms (3)

Standard of care

ACTIVE COMPARATOR

Other: Standard of care

Fostamatinib

ACTIVE COMPARATOR

Drug: Fostamatinib

Ruxolitinib

ACTIVE COMPARATOR

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Ruxolitinib is a Janus kinase 1 (JAK1)/Janus kinase 2 (JAK2) inhibitor approved for clinical use in the treatment of splenomegaly, myelofibrosis, polycythaemia vera and graft-versus-host disease. It is an oral agent with a rapid mode of action.

Ruxolitinib

Fostamatinib DRUG

Fostamatinib is a tyrosine kinase inhibitor with activity against spleen tyrosine kinase (SYK). It has approved for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP).

Fostamatinib

Standard of care OTHER

Standard of care treatment as per site-level policies and guidelines.

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients age ≥ 18 years at screening
• Patients with mild or moderate C19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale by
• Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected\* or laboratory-confirmed) AND Radiological change consistent with COVID-19 disease
• C-reactive protein (CRP) greater than or equal to 30mg/L
• Informed consent from patient or personal or professional representative
• No medical history that might, in the opinion of the responsible clinician, put the patient at significant risk if he/she were to participate in the trial
• Agreement to abstain from sexual intercourse or use contraception that is \>99% effective for all participants of childbearing potential for 42 days after the last dose of study drug. For male participants, agreement to abstain from sperm donation for 42 days after the last dose of study drug.
• Able to read English. Non-English speakers will be able to join the study. If patients are unable to understand verbal or written information in English - hospital translation services will be requested at the participating site for the participant where possible.

You may not qualify if:

• Requiring either invasive or non-invasive ventilation including CPAP or high flow nasal oxygen at any point after hospital admission and before baseline not related to a pre-existing condition (e.g. obstructive sleep apnoea)
• Grade ≥ 5 severity on the modified WHO COVID-19 Ordinal Scale, viz. O2 saturation \< 90% on ≥ 60% inspired oxygen at baseline; non-invasive ventilation; or invasive mechanical ventilation at any point since hospital admission.
• In the opinion of the investigator, progression to death is inevitable within the next 24 hours, irrespective of the provision of therapy
• Known severe allergic reactions to the investigational agents
• Child Pugh B or C grade hepatic dysfunction
• Use of drugs within the preceding 14 days that are known to interact with any study treatment (FOS or RUX), as listed in the Summary of Product Characteristics
• Pregnant or breast feeding
• Any medical condition or concomitant medication that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures.
• Any medical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study
• Pregnant or breast feeding

Sponsors & Collaborators

• Imperial College London: lead
• Imperial College Healthcare NHS Trust: collaborator
• Rigel Pharmaceuticals: collaborator
• Novartis: collaborator

Study Sites (5)

The Leeds Teaching Hospital - St James University Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

London North West University Healthcare

London, HA1 3UJ, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Royal Berkshire NHS Foundation Trust

Reading, RG1 5AN, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust - Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Vergis N, Phillips R, Cornelius V, Katsarou A, Youngstein T, Cook L, Willicombe M, Pilay C, Shturova T, Almonte M, Charania A, Turner R, Kon OM, Cooke G, Thursz M, Cherlin S, Wason J, Milojkovic D, Innes AJ, Cooper N. Multi-arm Trial of Inflammatory Signal Inhibitors (MATIS) for hospitalised patients with mild or moderate COVID-19 pneumonia: a structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Apr 12;22(1):270. doi: 10.1186/s13063-021-05190-z.

  PMID: 33845867 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19; Pneumonia

Interventions

ruxolitinib; fostamatinib; Standard of Care

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nichola Cooper

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 9, 2020
• Study Start: October 2, 2020
• Primary Completion: November 30, 2022
• Study Completion: September 2, 2023
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

GB (5)