mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Experimental Drugs and Mechanisms

NCT04393246 | Completed Phase 2 DMC

• 1 other identifier: TACTIC-E
• Study Type: interventional
• Target: 454
• Locations: 1 country
• Sites: 1

Brief Summary

TACTIC-E is a randomised, parallel arm, open-label platform trial for investigating potential treatments for COVID-19 disease. While SARS-CoV infection evades detection by the immune system in the first 24 hours of infection, it ultimately produces a massive immune system response in the subgroup of people who develop severe complications. Most tissue damage following infection with COVID-19 appears to be due to a later, exaggerated, host immune response (Gralinski and Baric 2015). This leads to lung and sometimes multi-organ damage. Most people who develop these severe complications still have virus present in their respiratory tract at the time-point when the disease starts to evolve. Immune modulation in the presence of active infection has potential to cause more harm than benefit. Safety considerations when studying immune modulation strategies are paramount. This study will assess the efficacy of a novel immunomodulatory agent and a novel combination of approved agents which may protect the patient against end-organ damage and modulate the pulmonary vascular response. This study will compare the novel therapeutic agent EDP1815 and a novel combination of the approved agents dapagliflozin and ambrisentan against Standard of Care. A trial arm (UNI911) with the IMP Niclosamide was added to the protocol with one patient recruited into this arm. Following an AESI and after discussions between the funder and the Sponsor the arm was stopped.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Time to incidence of the composite endpoint of: Death, Mechanical ventilation, ECMO, Cardiovascular organ support, or Renal failure

  Number of days taken for occurrence of one of the following events: 1. Death 2. Mechanical ventilation 3. Extracorporeal membrane oxygenation (ECMO) 4. Cardiovascular organ support (balloon pump or inotropes/vassopressors) 5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) \<15 ml /min/1.73m\^2), haemofiltration or dialysis

  up to Day 14

Secondary Outcomes (15)

• Change in biomarkers thought to be associated with progression of COVID-19 compared to baseline: IL-6

  14 days

• Change in biomarkers thought to be associated with progression of COVID-19 compared to baseline: ferritin

  14 days

• Change in biomarkers thought to be associated with progression of COVID-19 compared to baseline: c-reactive protein (CRP)

  14 days

• Change in biomarkers thought to be associated with progression of COVID-19 compared to baseline: D-dimer

  14 days

• Change in biomarkers thought to be associated with progression of COVID-19 compared to baseline: neutrophil/lymphocyte ratio

  14 days

Study Arms (3)

Standard of care

ACTIVE COMPARATOR

Standard of care

Other: Standard of care

EDP1815

EXPERIMENTAL

1.6 x 10\^11 cells dosage-in-capsule orally twice per day for up to 7 days (with the option to extend up to 14 days), on top of standard of care

Drug: EDP1815

Dapagliflozin and Ambrisentan

EXPERIMENTAL

Ambrisentan 5mg tablet orally once per day for up to a maximum of 14 days and Dapagliflozin 10mg tablet orally once per day for up to a maximum of 14 days, on top of standard of care

Drug: Dapagliflozin; Drug: Ambrisentan

Interventions

EDP1815 DRUG

EDP1815 is an orally administered pharmaceutical preparation of a single strain of Prevotella histicola isolated from the duodenum of a human donor. EDP1815 is currently in phase 2 clinical development and has European and US approval to initiate a multinational psoriasis study.

EDP1815

Dapagliflozin DRUG

Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT-2) inhibitor. Dapagliflozin is licensed for use in the UK for treatment of Type II diabetes. Since this trial is evaluating Dapagliflozin in an unlicensed indication, it is being carried out under a Clinical Trial Authorisation (CTA)

Also known as: Forxiga

Dapagliflozin and Ambrisentan

Ambrisentan DRUG

Ambrisentan is an endothelin receptor antagonist, and is selective for the type A endothelin receptor (ETA). Ambrisentan was approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and indicated for the treatment of pulmonary arterial hypertension.

Also known as: Letairis, Volibris, Pulmonext

Dapagliflozin and Ambrisentan

Standard of care OTHER

Regular standard of care for COVID-19 patients

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:

• Be aged 18 and over
• Have clinical picture strongly suggestive of COVID-19-related disease (with/without positive COVID-19 test) AND
• Risk count (as defined below) \>3 OR
• Risk count ≥3 if it includes "Radiographic severity score \>3"
• Be hospitalized or eligible for hospitalization on clinical grounds
• Be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator
• Is able to swallow capsules/tablets

You may not qualify if:

• Inability to supply direct informed consent from patient or from Next of Kin or Independent Healthcare Provider on behalf of patient
• Invasive mechanical ventilation at time of screening
• Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients
• Currently on any of the study investigational medicinal products
• Concurrent participation in an interventional clinical trial (observational studies allowed)
• Patient moribund at presentation or screening
• Pregnancy at screening
• Unwilling to stop breastfeeding during treatment period
• Known severe hepatic impairment (with or without cirrhosis)
• Requiring dialysis Cockcroft Gault estimated creatinine clearance \< 30 ml /min/1.73m2 at screening
• Inability to swallow at screening visit
• Patient is taking a systemic immunosuppressive agent such as, but not limited to, oral steroids, methotrexate, azathioprine, ciclosporin or tacrolimus, unless these are given as part of COVID standard of care treatment.
• Patient has known primary or secondary B cell disorder
• Type 1 diabetes
• Known idiopathic pulmonary fibrosis

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Related Publications (3)

• Gralinski LE, Baric RS. Molecular pathology of emerging coronavirus infections. J Pathol. 2015 Jan;235(2):185-95. doi: 10.1002/path.4454.

  PMID: 25270030 BACKGROUND

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

• Lu IN, Kulkarni S, Fisk M, Kostapanos M, Banham-Hall E, Kadyan S, Bond S, Norton S, Cope A, Galloway J, Hall F, Jayne D, Wilkinson IB, Cheriyan J. muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E): A structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Jul 31;21(1):690. doi: 10.1186/s13063-020-04618-2.

  PMID: 32736592 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

dapagliflozin; ambrisentan; Standard of Care

Condition Hierarchy (Ancestors)

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

• Joseph Cheriyan, MBChB MA FRCP

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant in Clinical Pharmacology

Model Details: TACTIC-E is a randomised, parallel arm, open-label platform trial

Study Record Dates

• First Submitted: May 16, 2020
• First Posted: May 19, 2020
• Study Start: July 3, 2020
• Primary Completion: June 1, 2022
• Study Completion: June 8, 2022
• Last Updated: July 28, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)