Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201411000939962 Date of Approval: 14/11/2014
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Rapid Assessment of Potential Interventions & Drugs for Ebola (RAPIDE) - BCV
Official scientific title Open-label, non-randomised single arm trial to investigate the efficacy of Brincidofovir compared to historic controls for Ebolavirus Disease in an outbreak setting in West Africa.
Brief summary describing the background and objectives of the trial The size and scale of the on-going Ebola Virus Disease (EVD) outbreak is unprecedented, shows no signs of abating, and has been declared a Public Health Emergency of International Concern. Ebola virus is among the most virulent infectious agents known and is associated with intense virus replication, severe disease and high mortality. Whilst several therapeutic interventions have shown promise in pre-clinical studies, none have been tested for efficacy and safety in humans with EVD. The aim of this protocol is to assess the effectiveness of Brincidofovir for the treatment of EVD. Brincidofovir (BCV; CMX001, Chimerix Inc.), available as a tablet, has demonstrated broad spectrum antiviral activity against various pathogenic human dsDNA viruses in vitro and in animal models. BCV has successfully completed Phase 2 clinical development for the prevention of cytomegalovirus (CMV) infection. Phase 2 and 3 studies of CMV prevention and treatment of adenovirus (AdV) viremia are ongoing. Pre-clinical work indicating potential efficacy against the Mayinga strain of Ebola Zaire combined with experience in over 1000 patients to show efficacy in other viral infections and providing safety and tolerability data, support the case for undertaking a phase IIB assessment of this drug in patients presenting with Ebola infection. BCV was selected for urgent evaluation from a possible list of 10 candidate therapies. The criteria for selection were based upon a Target Product Profile that considered existing clinical and pre-clinical data supporting safety and efficacy, immediate availability and scalability, and an acceptable treatment regimen. The aim of this protocol is to provide a safe, scientifically valid, ethical and operationally realistic mechanism for assessing Brincidofovir for the treatment of EVD as soon as possible. This protocol aims to rapidly assess efficacy and, to a very limited extent, safety of this un-registered therapeutic product in patients with EVD.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) RAPIDE
Disease(s) or condition(s) being studied Ebola Virus,Infections and Infestations
Sub-Disease(s) or condition(s) being studied Ebola
Purpose of the trial Treatment: Other
Anticipated trial start date 05/12/2014
Actual trial start date 02/01/2015
Anticipated date of last follow up 19/02/2015
Actual Last follow-up date 30/06/2015
Anticipated target sample size (number of participants) 140
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Brincidofovir (BCV) Patients >= 50 kg: 200 mg initial dose, then 100 mg twice weekly for 4 doses Patients <50 kg: 4mg/kg initial dose, then 2 mg/kg twice weekly for 4 doses 2 weeks BCV 140 Historical
Control Group Historical untreated survival rate N/A N/A Used historical data on outcomes of patients at treatment centre to calculate probability of survival 778 Historical
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Male and female patients 2 months of age or older Laboratory confirmed infection with Ebolavirus infection. Women who are lactating must agree to stop breastfeeding (a standard recommendation for all EVD patients) Willingness to use barrier birth control for 3 months after recovery of EVD (a standard recommendation for all EVD patients) For patients 18 years and older: the ability to provide fully informed consent or the provision of consent from the representative of a patient deemed too unwell to comprehend what is being asked of them. For patients under 18 years: consent from a parent or guardian. Any underlying disease or condition that, in the opinion of the principal investigator or treating physician, could jeopardize the participant¿s or healthcare workers safety or the participant¿s ability to comply with the protocol requirements Patient unable to take oral IMP (e.g. severe vomiting unresponsive to anti-emetics, unconscious) Pregnancy 2 Month(s) 99 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/11/2014 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
University of Oxford, Joint Research Office, Block 60, Churchill Hospital Oxford OX3 7LE United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/11/2014 University of Liberia-Pacific Institute for Research & Evaluation Institutional Review Board (UL-PIRE IRB)
Ethics Committee Address
Street address City Postal code Country
Capitol Hill Monrovia Liberia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Mortality at Day 14 after entry into the trial Day 14
Secondary Outcome Time to meeting EVD treatment center discharge criteria daily until discharge
Secondary Outcome Mortality at Day 30 after first dose of study treatment Day 30
Secondary Outcome Day 4 viral load Day 4
Secondary Outcome Presence and duration of symptoms Day 0-14
Secondary Outcome Convalescent anti-Ebolavirus IgG titer Day 30
Secondary Outcome Incidence of SARs and key adverse events Day 0-14
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
ELWA3 Monrovia Liberia
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome Trust 215 Euston Road London NW1 2BE United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford Joint Research Office, Block 60, Churchill Hospital Oxford OX3 7LE United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Iza Ciglenecki Médecins Sans Frontières, 78 rue de Lausanne, Case Postale 116 Geneva 1211 Switzerland
Annick Antierens Médecins Sans Frontières, Rue Dupré 94 Brussels 1090 Belgium
Trudie Lang University of Oxford, NDMRB, Old Road Campus, Roosevelt Drive Oxford OX3 7FZ United Kingdom
Piero L Olliaro University of Oxford, NDMRB, Old Road Campus, Roosevelt Drive Oxford OX3 7FZ United Kingdom
Jake Dunning University of Oxford, NDMRB, Old Road Campus, Roosevelt Drive Oxford OX3 7FZ United Kingdom
John Whitehead Department of Mathematics and Statistics, Fylde College, Lancaster University Lancaster LA1 4YF United Kingdom
Stephen Kennedy Pacific Institute for Research and Evaluation, University of Liberia Monrovia Liberia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Peter Horby peter.horby@ndm.ox.ac.uk +441865612974 Nuffield Department of Medicine Research Building
City Postal code Country Position/Affiliation
Oxford OX3 7FZ United Kingdom University of Oxford
Role Name Email Phone Street address
Public Enquiries Raul Pardinaz-Solis raul.pardinaz-solis@ndm.ox.ac.uk +44 01865 612 977 NDM Research Building
City Postal code Country Position/Affiliation
Oxford OX3 7FZ United Kingdom University of Oxford
Role Name Email Phone Street address
Scientific Enquiries Peter Horby peter.horby@ndm.ox.ac.uk +441865612974 NDM Research Building
City Postal code Country Position/Affiliation
Oxford OX3 7FZ United Kingdom University of Oxford
Role Name Email Phone Street address
Scientific Enquiries Catrin Moore catrin.moore@ndm.ox.ac.uk +441865612964 NDM Research Building, Centre for Tropical Medicine, Roosevelt Drive
City Postal code Country Position/Affiliation
Oxford OX3 7FZ United Kingdom University of Oxford
REPORTING
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Result URL Hyperlinks
Changes to trial information