Coronavirus-induced disease (COVID-19) (SARS coronavirus 2, or SARS-CoV-2) MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Nomacopan
Product Code: rVA576
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Nomacopan
Other descriptive name: VA576
Concentration unit: mg milligram(s)
Co
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Master Protocol: Patients are eligible to be included in the study only if all of the following criteria apply (as well as all criteria from the appropriate candidate-specific trial protocol): 1. Adults (=18 years) with laboratory-confirmed* SARS-CoV-2 infection (PCR) 2. Ability to provide informed consent signed by study patient or legally acceptable representative 3. Women of childbearing potential (WOCBP) and male patients who are sexually active with WOCBP must agree to use a highly effective method of contraception from the first administration of trial treatment, throughout trial treatment and for the duration outlined in the candidate-specific trial protocol after the last dose of trial treatment *If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible. Standard additional criteria that may be applied per candidate-specific trial protocol: Group A (severe disease) Patients with clinical status of Grades 5 (hospitalised, oxygen by mask or nasal prongs), 6 (hospitalised, non-invasive ventilation or high flow oxygen), 7 (hospitalised, intubation and mechanical ventilation, pO2/FiO2 =150 or SpO2/FiO2 =200), 8 (hospitalised mechanical ventilation pO2/FiO2 94% RA. Nomacopan Candidate-Specific Trial: Additional inclusion criteria specific to this CST are: 1. Adults (=18 years) with laboratory-confirmed SARS-CoV-2 infection (PCR) who are within 5 days of symptom onset. 4. A score of grade 4, 5, 6 or 7 on the 9-Point Ordinal Scale* Grade 6 and 7 will only be accepted when second cohort open to recruitment. CST-2 (EIDD-2801) additional inclusion criteria: 5. Has signs or symptoms of COVID-19 that began within 5 days of the planned first dose of study drug. 6. Is in generally good health (except for current respiratory infection) and is free of uncontrolled chronic conditions. 7. Is willing and able to comply with all study procedures and attending weekly clinic visits through the 4th week. 8. Has someone, aged = 16 living in the same household during the dosing period. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Master Protocol: Patients are excluded from the study if any of the following criteria apply (as well as all criteria from the appropriate candidate-specific trial protocol): 1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 times the upper limit of normal (ULN) 2.Stage 4 severe chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration rate <30 mL/min/1.73 m2) 3.Pregnant or breast feeding 4. Anticipated transfer to another hospital which is not a study site within 72 hours 5. Allergy to any study medication 6. Patients taking other prohibited drugs (as outline in CST protocol) within 30 days or 5 times the half-life (whichever is longer) of enrolment 7. Patients participating in another CTIMP trial Nomacopan Candidate-Specific Trial: For the purpose of the nomacopan candidate-specific trial, appendix exclusion criteria 6 has been amended from the Master protocol as follows, to restrict the population of patients that will be included in the trial: 6. Patients taking the following prohibited drugs: • Other complement inhibiting drug such as eculizumab (Soliris®). • Any other drug which directly inhibits cytokines, chemokines or proinflammatory mediators such as tocilizumab (Actemra®/RoActremra®), anakinra (Kineret®), etanercept (Enbrel®), infliximab (Remicade®) or adalimumab (Humira®). N.B. Whilst it is not thought that there is likely to be any adverse interaction between nomacopan and any of these drugs, in the context of a clinical trial, it would be impossible to distinguish the effects of those agents from that of nomacopan. Corticosteroids, antivirals and antibiotics are permitted in conjunction with nomacopan therapy. Additional exclusion criteria specific to this candidate specific appendix are: 8. Weight less than 50kg or more than 100kg CST-2 (EIDD-2801) additional exclusion criteria: 8. Has a febrile respiratory illness that includes pneumonia that results in hospitalisation, or requires hospitalisation, oxygenation, mechanical ventilation, or other supportive modalities. 9. Has a platelet count less than 50x10^9/L. 10. Is experiencing adverse events or laboratory abnormalities that are Grade 3 or above based on the CTCAE v5 grading. 11. Has clinically significant liver dysfunction or renal impairment. 12. Has history of Hepatitis C infection or concurrent bacterial pneumonia. 13. Has received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 30 days prior to the first dose of study drug. 14. In the opinion of the investigator, has significant end-organ disease as a result of relevant comorbidities: chronic kidney disease, congestive heart failure, peripheral vascular disease including diabetic ulcers. 15. Has a SaO2<95% by oximetry or has lung disease that requires supplemental oxygen or maintenance steroids. 16. Has any condition that would, in the opinion of the investigator, put the patient at increased risk for participation in a clinical study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Master Protocol: Phase I - To find the optimal dose of each drug (candidate) (or combination of candidates) Phase II - To determine the effect each candidate has on improving patients clinical outcome (using the WHO clinical severity score) and safety of each candidate and recommend whether it should be evaluated further in a large phase II/III trial. ;Secondary Objective: Master Protocol: Phase I - How safe is the treatment Phase II: To assess the effects of study treatments on: - The need for (and duration) of oxygen support (including mechanical ventilation) - The length of time people remain in hospital (including time in intensive care) - Clinical improvement at various timepoints - Side effects seen In addition in EIDD-2801-Candidate Specific Trial 2 - Patient Reported Outcomes;Primary end point(s): Master Protocol Co-primary endpoints: For dose finding (phase I) • Dose limiting toxicities (Safety and Tolerability of drug under study – CTCAE v5 Grade =3 adverse events) For efficacy evaluation (phase II) one of the following depending on the population the candidate is being evaluated in: • Group A (severe disease) Time to clinical improvement: Improvement will be determined according to the WHO Progression Scale. Improvement, defined by a minimum 2-step change in the scale, will be analysed as time to event, measured up to 29 days from randomisation. • Group B (mild-moderate disease) Pharmacodynamics of drug defined as time to negative viral titres in nose and/or throat swab, measured up to 29 days from randomisation. Nomacopan Candidate-Specific Trial: Time to clinical improvement: improvement will be determined according to the WHO clinical severity score (WHO Working Group on the Clinical Characteristics of COVID-19 infection 9-point ordinal scale). Improvement, defined by a minimum 2-step change in the scale, will be analysed as time to event, measured up to day 29. For CST-2 (EIDD-2801): To determine the safety and tol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Master protocol: Phase I: Safety: Adverse event rate according to CTCAE v5 Phase II: • Proportion of patients with clinical improvement (as defined above) at day 8, 15 and day 29 • Change at day 8 and 15 from randomisation in the WHO Clinical Progression Scale • Time to a one point change on the WHO Clinical Progression Scale • The ratio of the oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2) • Time to discharge from randomisation • Proportion of patient discharged by days 8, 15 and 29 • Admission rate and time in ICU • White cell count, haemoglobin, platelets, creatinine, and ALT on day 1, 3, 5, 8, 11 (while hospitalised); and Day 15 and 29 • Mortality at Days 8, 15 and 29 • Time to death from registration • Duration (days) of oxygen use and oxygen-free days • Duration (days) of mechanical ventilation and mechanical ventilation-free days • Incidence of new mechanical ventilation use and duration (days) of new mechanical ventilation use • Actual versus planned candidate treatment received • NEWS2 assessed daily while hospitalised • Change in viral load over time • SARS-CoV-2 in OP swab at baseline • Biomarkers for response Nomacopan candidate-specific protocol - No additional secondary endpoints. CST-2 (EIDD-2801) • Concentrations of EIDD-2801 and -1931 in plasma, nasal swab, tears, blood spots (Ph I & II) • Qualitative (and quantitative when possible) PCR for SARS-CoV-2 by nasal swab. (Ph I) • Patient Reported Outcome Measures (Ph I & II) • Actual versus planned treatment (Ph I & II) ;Timepoint(s) of evaluation of this end point: Timepoints outline within secondary endpoints outlined above. | — |
Countries
United Kingdom
Contacts
Public ContactEllice Marwood
Southampton Clinical Trials Unit
Outcome results
None listed