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.: PACTR202010817169062 Date of Approval: 05/10/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Pharmacokinetics, tolerability and safety of favipiravir compared to ribavirin for the treatment of Lassa Fever: A randomized controlled open label phase II clinical trial
Official scientific title Pharmacokinetics, tolerability and safety of favipiravir compared to ribavirin for the treatment of Lassa Fever: A randomized controlled open label phase II clinical trial
Brief summary describing the background and objectives of the trial Lassa fever in West Africa, including Nigeria, is of public health concern. It is listed as a priority disease for urgent research and development in the World Health Organisation (WHO) blueprint for action to prevent epidemics. There is no vaccination available for use in humans and only one drug with poor evidence of therapeutic efficacy is available (ribavirin). Favipiravir is a promising new drug that showed efficacy against Lassa fever in preclinical studies. It is already approved for treatment of pandemic influenza virus infections in Japan and is currently used in clinical studies for the treatment of severe influenza in the US. Before evaluating its efficacy to reduce the case fatality rate in Lassa fever, the optimal use of favipiravir must be understood. The aim of this phase II clinical study is to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of favipiravir in patients with Lassa fever with the ultimate goal of improving patient care.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SAFARI
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Lassa Fever
Purpose of the trial Treatment: Drugs
Anticipated trial start date 02/05/2021
Actual trial start date 30/07/2021
Anticipated date of last follow up 01/12/2022
Actual Last follow-up date 17/11/2022
Anticipated target sample size (number of participants) 40
Actual target sample size (number of participants) 40
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
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Ribavirin Irrua regimen 100 mg/kg Day 1(2/3 stat, 1/3 8 hours later), then 25 mg/kg days 2-7, 12.5 mg/kg days 8-10 10 days Ribavirin is the currently used antiviral for Lassa fever treatment, which is also recommended by the WHO. 20 Active-Treatment of Control Group
Experimental Group Favipiravir Day 1 2400mg-2400mg-1200mg, Day 2-10 1200mg BD 10 days Favipiravir is a promising new drug that showed efficacy against LF in preclinical studies. During the West-African Ebola outbreak it has been evaluated for the treatment of Ebola Virus disease. It is approved for treatment of pandemic influenza virus infections in Japan and currently in clinical studies for the treatment of severe influenza in the US. 20
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Age ≥ 18 years Lassa fever confirmed by PCR Written informed consent Inability to give consent (e.g. unconscious patients/ cognitively impaired patients) Women who plan to get pregnant within the upcoming 6 months Severe malnutrition (BMI<16) Pregnancy/lactation (evidenced by negative urine pregnancy test in women of child-bearing potential) Known intolerance to ribavirin or favipiravir History of hemoglobinopathies (i.e., sickle-cell anaemia or thalassemia major) and/or haemophilia Organ failure as evidenced by: o Creatinine ≥ 3x ULN o ALT/ AST > 150 IU/l o ACVPU score = V or P or U (corresponds to GCS ≤ 12) o Severe central nervous system features (e.g. seizures, restlessness, confusion or coma) o O2 Saturation < 90% o Hematocrit <30 % o Severe anaemia requiring blood transfusion Inability to take oral drug (e.g. encephalopathy, severe vomiting) Patients who already received ribavirin or favipiravir within the preceding 7 days 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 110 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 14/09/2021 National Health Research Ethics Committee of Nigeria
Ethics Committee Address
Street address City Postal code Country
Federal Secretariat Complex Shehu Shagari Way, Garki, Abuja P.M.B. 083, Garki-Abuja Abuja 0000 Nigeria
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 25/01/2021 Ethik Kommission der Aerztekammer Hamburg
Ethics Committee Address
Street address City Postal code Country
Weidestrasse 122b, 22083 Hamburg, Germany Hamburg 22083 Germany
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 14/09/2021 ISTH HREC
Ethics Committee Address
Street address City Postal code Country
KM 87, Benin Auchi Road Irrua 0000 Nigeria
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 15/02/2021 FMCO ethics
Ethics Committee Address
Street address City Postal code Country
Michael Adekunle Ajasin Road Owo 0000 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Description of classical pharmacokinetic parameters of favipiravir (e.g. Cmax, Tmax, AUC, T1/2, VOD, etc.) in patients with PCR confirmed LF after drug administration
Primary Outcome Proportion of drug related AEs and SAEs- Safety and tolerability of ribavirin and favipiravir in investigated regimens after drug administration
Secondary Outcome Mutagenicity of ribavirin and favipiravir measured via nucleotide exchange rate in individual Lassa virus genomes before and after treatment
Secondary Outcome Description of RNA concentrations, infectious titers and serological status during treatment before and after treatment
Secondary Outcome PK modelling and simulation of different loading regimens to characterise time to target concentration attainment after drug administration
Secondary Outcome Relationship between drug exposure (AUC, Cl/F) and i. Viral elimination dynamics (elimination rate constant), including time to viral clearance ii. Length of hospital stay iii. Mortality iv. Blood component therapy use after treatment
Secondary Outcome Co-variates impacting on drug exposure before and after treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Irrua Specialist Teaching Hospital Km 87 Benin-Auchi Road Irrua Nigeria
Federal Medical Centre Owo Michael Adekun Aiasin Road, P.M.B. 1053 Owo Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Bundesministerium fuer Gesundheit Friedrichstrasse 108 Berlin 11055 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Bernhard Nocht Institute for Tropical Medicine Bernhard-Nocht-Strasse 74 Hamburg 20359 Germany Foundation under Public Law
COLLABORATORS
Name Street address City Postal code Country
INSERM Universite de Bordeaux 146 Rue Leo Saignat Bordeaux 33076 France
Alliance for International Medical Action 15 rue des immeubles industriels Paris 75011 France
Institute of Pharmacy University of Hamburg Bundesstrasse 45 Hamburg 20146 Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Peter Akhideno ehideno@yahoo.co.uk +2348037048831 KM 87 Benin Auchi Rd
City Postal code Country Position/Affiliation
Irrua Nigeria Principal Investigator ISTH
Role Name Email Phone Street address
Scientific Enquiries Michael Ramharter ramharter@bnitm.de +494042818511 Bernhard-Nocht-Strasse 74
City Postal code Country Position/Affiliation
Hamburg 20359 Germany Head of Clincial Research
Role Name Email Phone Street address
Public Enquiries Mirjam Groger groger@bnitm.de +494042818480 Bernhard-Nocht-Strasse 74
City Postal code Country Position/Affiliation
Hamburg 20359 Germany Project Coordinator
Role Name Email Phone Street address
Principal Investigator Cyril Erameh cyrilerameh@gmail.com +2348032413382 KM 87 Benin Auchi Rd
City Postal code Country Position/Affiliation
Irrua Nigeria Co Principal Investigator ISTH
Role Name Email Phone Street address
Principal Investigator Ayodeji Oladele Oluwafemi emiayodeji@yahoo.com +2348035767632 Michael Adekun Ajasin Road, P.M.B. 1053
City Postal code Country Position/Affiliation
Owo Nigeria Principal Investigator FMCO
Role Name Email Phone Street address
Principal Investigator Abiodun Abidoye atabidoye233@yahoo.com +2347033276118 Michael Adekun Ajasin Road, P.M.B. 1053
City Postal code Country Position/Affiliation
Owo Nigeria Co Principal Investigator FMCO
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes In line with the funding conditions, IPD is to be shared. However, this will be de-identified IPD that used to generate the results reported (text, tables, figures and appendices). IPD sharing will begin after publication of primary results and will be available for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. The IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. Clinical Study Report,Informed Consent Form,Study Protocol From the time of publication and for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. This IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The data shall be made available through a governed data access process which includes a transparent, accountability and decision-making process: Completion of data request form Evaluation by a data access committee Data sharing Agreement Secure transfer of data
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information