DEFINE - Evaluating Therapies for COVID-19

• Status: Active, not recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

COVID-19 is a community acquired pneumonia caused by infection with a novel coronavirus, SARS CoV2 and is a serious condition with high mortality in hospitalised patients, for which there is no currently approved treatment other than supportive care. Urgent investigation of potential treatments for this condition is required.

This protocol describes an overarching and adaptive trial designed to provide safety, pharmacokinetic (PK)/ pharmacodynamic (PD) information and exploratory biological surrogates of efficacy which may support further development and deployment of candidate therapies in larger scale trials of COVID-19 positive patients receiving normal standard of care.

Given the spectrum of clinical disease, community based infected patients or hospitalised patients can be included. Products requiring parenteral administration will only be investigated in hospitalised patients. Patients will be divided into cohorts, a) community b) hospitalised patients with new changes on a chest x-ray (CXR) or a computed tomography (CT) scan or requiring supplemental oxygen and c) hospitalised requiring assisted ventilation. Participants may be recruited from all three of these cohorts, depending on the experimental therapy, its route of administration and mechanism of action. The relevant cohort(s) for any given therapy will be detailed in the therapy-specific appendix.

Candidate therapies can be added to the protocol and previous candidates removed from further investigation as evidence emerges. The trial will be monitored by an independent Data Monitoring Committee (DMC) to ensure patient safety.

Each candidate cohort will include a small cohort of patients randomised to candidate therapy or existing standard of care management dependent on disease stage at entry. Cohort numbers will be defined in the protocol appendices.

This is a Phase IIa experimental medicine trial and as such formal sample size calculations are not appropriate.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Edinburgh
• Collaborators: Latus Therapeutics; University of Oxford
• Treatments: Nafamostat

Criteria

Inclusion Criteria:

• Provision of informed consent from the patient or representative

• Aged at least 16 years

• If the patient is of child bearing potential, the patient, and their partner(s), agree to use medically-accepted double-barrier methods of contraception (eg, barrier methods, including male condom, female condom or diaphragm with spermicidal gel) during the study (if randomised to a treatment arm) and for at least 90 days after termination of study therapy. A vasectomised partner would be considered an appropriate birth control method provided that the partner is the sole male sexual partner and the absence of sperm has been confirmed.

• COVID-19 positive

Exclusion Criteria:

• Current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled cardiac disease (NYHA class IV), uncontrolled renal disease (eGFR <30 mL/min/1.73 m2), severe liver dysfunction (ALT/AST >5x ULN) or bone marrow failure (Hb <80 g/L AND ANC<0.5 mm3 AND platelet count <50,000 uL)

• Women who are pregnant or breastfeeding.

• Participation in another clinical trial of an investigational medicinal product (CTIMP)

• Known hypersensitivity to the IMP or excipients (e.g. lactose)

• Pre-existing or Cconcomittant use of off-label treatments for COVID-19 that are not recognised as locally approved standard care.

• Significant electrolyte disturbance (hyperkalaemia potassium >5.0 mmol/L or hyponatraemia sodium < 120mmol/L)

• Patient currently receiving potassium sparing diuretics that cannot be reasonably withheld

• Patient currently receiving prophylactic or therapeutic anticoagulantsanticoagulation or antiplatelet agents that cannot be reasonably withheld if randomised to Nafamostat

• Patients (or their partners) planning on donating sperm/eggs during the trial period

• Ongoing dialysis

• History of serious liver disease (Child Pugh score > 10)

• Hemoglobin < 80 g/L

• Any known allergy to the IMP/excipients

• Severe uncontrolled diabetes mellitus

• In the Investigator's opinion, patient is unwilling or unable to comply with drug administration plan, laboratory tests or other study procedures.