COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001736-95/GB

University Hospital Southampton NHS Foundation Trust - Emma Perry

sponsor@uhs.nhs.uk

2020-04-23

Recruiting

RCT

Randomized

Adaptive

Open label

multi-center

Treatment

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 sub-protocol): 1. Adults (≥18 years) with SARS-CoV-2 infection confirmed by laboratory tests and/or point of care tests (which may include results from a test that was performed prior to hospital admission if, in the opinion of the Investigator, it is relevant to ongoing COVID-19). 2. Patients with symptoms and/or signs consistent with COVID-19, requiring treatment. 3. A score of Grade 3 to 5 on the 9-point ordinal scale. 4. a) Male patients: A male patient must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. b) Female patients: A female patient is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least 1 of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5. OR ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 90 days after the last dose of study treatment. 5. Women who are lactating who agree not to breastfeed their child during the study and for a fixed period of time (following guidance that will be given by the investigator as appropriate for any candidate agent administered) after termination of study therapy (they may continue to express milk away from the child during this period, but this milk must be discarded). 6. Ability to provide informed consent signed by the study patient or legally authorised representative. In addition for the sub-protocol ACCORD-2-006: Antibiotic prophylaxis: PLEASE NOTE that, according to Protocol Section 4.1.1.1, all patients must take antibiotic prophylaxis concomitantly, starting with the first dose of zilucoplan. For the sub-protocol ACCORD-2-002: Inclusion criteria 4 and 5 will be modified from the Master Protocol, as the contraception requirements will need to be for 120 days (not 90 days) after termination of study therapy, and breastfeeding restrictions will be for a similar time period. The revised criteria will be as follows: 4.a) Male patients: A male patient must agree to use contraception as detailed in Appendix 5 of the Master Protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. b) Female patients: A female patient is eligible to participate if she is not pregnant (see Appendix 5 of the Master Protocol), not breastfeeding, and at least 1 of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 of the Master Protocol. OR ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 of the Master Protocol during the treatment period and for at least 120 days after the last dose of study treatment. 5. Women who are lactating who agree not to breastfeed their child during the study and for at least 120 days after termination of study therapy (they may continue to express milk away from the child during this period, but this milk must be discarded).

Patients are excluded from the study if any of the following criteria apply (or any of the criteria from the appropriate sub-protocol): 1. Patients who have previously had a score of 6 or 7 on the 9-point ordinal scale. 2. Any patient whose interests are not best served by study participation, as determined by a senior attending clinician. 3. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × the upper limit of normal (ULN). 4. Known active infection with HIV or hepatitis B or C. 5. Stage 4 severe chronic kidney disease. 6. Allergy to any study medication. 7. Experimental off-label usage of medicinal products as treatments for COVID-19 (except where the product has either been given a positive opinion under the Early Access to Medicines Scheme [EAMS] or is a SARS-CoV-2 vaccine) at the time of enrolment. 8. Patients participating in another clinical study of an investigational medicinal product, unless co-enrolment in the other study has been pre-approved by the Sponsor and Chief Investigator. 9. Active tuberculosis defined as requiring current treatment for tuberculosis. Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-002: X1. Inability to swallow capsules (administration via nasogastric tube is permitted in patients who become unable to swallow after starting the study drug) X2. Patients with a permanent cardiac pacemaker implanted. X3. History of the following cardiac conditions: a) Myocardial infarction within 3 months prior to the first dose b) Unstable angina c) History of clinically significant dysrhythmias (long QT features on ECG, sustained bradycardia [≤55 bpm]), left bundle branch block, or ventricular arrhythmia) or history of familial long QT. Patients with an implantable cardioverter defibrillator device in place, will be allowed to enrol. Atrial fibrillation will not be a reason for exclusion. X4. Screening 12-lead ECG with a measurable QTc interval according to Fridericia correction (QTcF) >470 msec In the presence of a temporary cardiac pacemaker, QTcF will need to be calculated from an ECG which has been recorded during a period where ventricular (QRS) complexes without pacing are present. If no unpaced ventricular complexes are present to allow calculation of QTcF, the patient should not be enrolled in this sub-protocol. X5. Clinically significant hypokalaemia. Individuals who do not meet this criterion may be rescreened once, after correction of electrolyte abnormality X6. Therapeutic anticoagulation with vitamin K antagonists. Note: Patients receiving low doses prescribed to maintain the patency of venous access devices may be included. X7. Previous bowel resection that would interfere with drug absorption Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-003: X1. A known history of myocardial infarction within 3 months prior to the first dose X2. A known history of heart failure defined as either of the following: a) ≥2 first degree relatives with clinically significant heart failure, or b) ≥1 first degree relative with heart failure known to be heritable (eg, hypertrophic cardiomyopathy), unless inheritance was previously excluded by genetic testing Additional exclusion criteria that are specific to the sub-protocol ACCORD-2-006: X1.Participants with unresolved or suspected infection with Neisseria meningitidis, or a past history of Neisseria meningitidis (eg, in a complement deficient patient), should not receive treatment with zilucoplan.

5

University Hospital Southampton NHS Foundation Trust

18

None

United Kingdom

Moderate/severe disease at enrollment

4: Moderate/severe disease at enrollment

1800

•Time to sustained clinical improvement of at least 2 points (from randomisation) on a 9 point category ordinal scale, live discharge from the hospital, or considered fit for discharge (a score of 0, 1, or 2 on the ordinal scale), whichever comes first, by Day 29 (this will also define the “responder” for the response rate analyses). 9-point category ordinal scale: 0. Uninfected, no clinical or virological evidence of infection 1. Ambulatory, no limitation of activities 2. Ambulatory, limitation of activities 3. Hospitalised – mild disease, no oxygen therapy 4. Hospitalised – mild disease, oxygen by mask or nasal prongs 5. Hospitalised – severe disease, noninvasive ventilation or high flow oxygen 6. Hospitalised – severe disease, intubation and mechanical ventilation 7. Hospitalised – severe disease, ventilation and additional organ support – vasopressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO) 8. Death *************** Sub-protocol-ACCORD-2-002, 003 & 006: As defined in Master Protocol.

nan

Phase 2

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