Pharmacokinetics, Tolerability and Safety of Favipiravir Compared to Ribavirin for the Treatment of Lassa Fever: A Randomized Controlled Open Label Phase II Clinical Trial
Phase: PHASE2
Conditions: Lassa Fever
Sponsor: Bernhard Nocht Institute for Tropical Medicine

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 1 of 9 
 
 
This Informed Consent Form is for men and women who attend Irrua Specialist Teaching 
Hospital (ISTH), and who we are inviting to participate in research on Lassa Fever. The title of 
our research project is as follows.  
 
Title of the research: Pharmacokinetics, tolerability and safety of favipiravir compared to 
ribavirin for the treatment of Lassa fever: A randomized controlled open label phase II clinical 
trial 
 
Name(s) and affiliation(s) of researcher(s) of applicant(s): This study is being conducted by 
Dr. Peter Akhideno (Principal Investigator) of the Irrua Specialist Teaching Hospital (ISTH) in 
Edo State, Nigeria and by Dr. Cyril Erameh (Co-Principal Investigator) of the Irrua Specialist 
Teaching Hospital (ISTH) in Edo State, Nigeria, and Prof. Stephan Günther of the Bernhard 
Nocht Institute for Tropical Medicine in Hamburg, Germany.  
 
Sponsor(s) of research: The sponsor of this study is the Bernhard-Nocht-Institute for Tropical 
Medicine, Hamburg, Germany. The sponsor representative is Prof. Stephan Günther, 
Department of Virology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany. 
 
Funding: The research is funded by the German Federal Ministry of Health. 
 
Introduction: The ISTH and the Bernhard-Nocht-Institute for Tropical Medicine in Germany 
as well as the Federal Medical Center of Owo (FMCO) Ondo State, Nigeria, the Institut national 
de la santé et de la recherche médicale (Inserm), France and the Alliance for International 
Medical Action (ALIMA), France, are doing research on the treatment of Lassa fever. You have 
been diagnosed with Lassa fever. Therefore, you are being invited to volunteer as a participant 
in this research being conducted by ISTH. The same study is also conducted at FMCO. Before 
you decide whether you want to participate in this research or not, it is important for you to 
understand why the research is being done and what it will involve. You will have sufficient 
time to consider whether or not you would like to participate in the research. Please read through 
the following information carefully and feel free to ask any questions if it is not clear or to 

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 2 of 9 
 
discuss it with anyone you wish. There may be some words that you do not understand. Please 
feel free to ask the research physician (investigator) who is informing you about this study. 
There will be time to explain all details, to address all your questions and time for you to 
consider your participation.  
 
Purpose(s) of research: Lassa fever is an acute febrile illness with bleeding and organ failure. 
The Lassa virus, which is spread by rodents, is responsible for this illness. There is no 
vaccination available against the Lassa virus. There is only one drug known for treatment of 
Lassa fever which is called ribavirin. The knowledge of the efficacy of this drug in Lassa fever 
treatment is poor. Favipiravir is a drug candidate that showed efficacy against Lassa fever in 
non-human research. It has also been evaluated for use during the West-African Ebola outbreak 
and is approved for the treatment of widespread influenza virus infections in Japan. In order to 
evaluate the efficacy of favipiravir in Lassa fever, it is necessary to compare this new treatment 
candidate to the standard of care. We therefore conduct a randomized study with two treatment 
arms. This means that one of two treatment options will be allocated to you by chance. 
 
Participation selection: We are inviting all (if female: non-pregnant) adults with Lassa fever 
who attend ISTH to participate in this research. Pregnant women, minors and cognitively 
impaired patients will be excluded from the research because, as a vulnerable population, they 
should not be exposed to the additional burden of an interventional study. Furthermore, 
intravenous ribavirin is not suitable for children and pregnant women. In case you are not able 
to take oral drugs (favipiravir will be administered orally) you may not be eligible. 
 
Voluntariness: Your participation in this research is entirely voluntary. It is your choice 
whether to participate or not. If you choose not to participate in this research project, you will 
be offered the standard of care for Lassa fever treatment which is ribavirin. This treatment is 
routinely offered in this hospital for the treatment of Lassa fever. You also may change your 
mind later and stop participating even if you have agreed earlier. 
 
Alternatives to participation: If you choose not to participate, this will not affect your 
treatment in this hospital in any way. 

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 3 of 9 
 
 
Procedure of the research, what shall be required of each participant and approximate 
total number of participants that would be involved in the research: If you decide to 
participate in the study, one of the following treatment options will be allocated to you by 
chance: 
1. Intravenous ribavirin standard treatment 
2. Oral favipiravir  
 
You will further be asked to provide blood. In total there will be 10 additional blood draws. 75 
ml blood will be drawn in addition to the routine care which corresponds to approximately 5 
tablespoons of blood. The routine care includes at least 8 blood draws and 49 ml of blood 
(corresponding to approximately 3.5 tablespoons) which will be withdrawn. Sampling will stop 
at discharge. The sampling frequency is planned as follows: To determine the ribavirin or 
favipiravir blood levels, blood collection will take place at 0.5, 1, 3, 5, 8 and 12 hours after as 
well as before the first drug administration. Furthermore, blood collection for determination of 
ribavirin or favipiravir blood levels will be performed once daily on day 2, 4, 6, 8, 10 and three 
times daily on day 7. On day 1 and 7 the blood may be taken with the help of a venous catheter 
which will stay in your vein for up to 13 hours on these days so that there will be less punctures 
and the blood is easier accessed. Blood for viral load measures will be taken at recruitment, 
before and 24 hours after first drug administration and on the 4th, 6th, 8th and 10th day of drug 
administration. Blood for general analyses (biochemical and haematology) will be collected 
every other day starting with screening. Whenever possible, collecting blood for research 
purposes is done in conjunction with routine blood collection to prevent additional 
interventions. If blood will be taken without a venous catheter, it will be taken with a syringe 
and needle. In total 124 ml blood will be drawn from you which corresponds to 8.5 tablespoons 
of blood. The additional amount of blood which is taken for research purposes amount to 75 ml 
(= 5 tablespoons) and is included in this 124 ml. Sampling will stop at day 10.  
 
 
The blood will be tested in the laboratory for several parameters to find out how the drugs works 
in your body. In addition, your symptoms along the disease/your stay at the hospital will be 

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 4 of 9 
 
recorded, vital signs and body temperature will be measured regularly, ECG measurements as 
well as physical examinations will be performed and your urine will be analysed. 
The research is conducted by staff of the Institute of Lassa Fever Research and Control at ISTH 
in collaboration with your doctor, as well as specialized laboratories. Part of your blood will 
also be sent to and tested by our German collaboration partners at the Bernhard-Nocht-Institute 
for Tropical Medicine, Hamburg and at the Institute of Pharmacy, University of Hamburg. This 
blood will be shipped according to the respective regulations. Your blood will be shipped in a 
pseudonymized manner (there will be no link to your name). Please see also the chapter 
“Confidentiality”.    
A total of 40 evaluable patients with Lassa fever are expected to participate (20 per treatment 
option). 
 
What happens to your blood samples: The biologicals materials are to be stored at the 
Bernhard-Nocht-Institute for Tropical Medicine, BNITM, Hamburg, Germany and used at the 
laboratories of the BNITM and collaborators under BNITM’s direct or delegated supervision 
as specified in the research protocol approved by the Institutional HREC. The blood samples 
will be stored securely for up to 10 years. It may become necessary to redo the analysis at a 
later time to confirm the results. The remaining blood samples will be destroyed according to 
the institutions’ Standard Operating Procedure as well as to applicable regulations.  
In order to improve the general health of the population and help the countries to put in place 
the right preventive measures, it could also occur that your blood may be needed to perform 
more analysis for Lassa fever and/or for other diseases that you might have been exposed to (it 
is possible to know this by testing the blood you gave along the study). These additional 
analyses would be conducted following internationally accepted standards (e.g. approval by 
ethics committee if applicable) and your identifier would be removed from your identifiable 
blood samples. That way your blood samples could be used without your additional informed 
consent. 
Expected duration of research and of participant(s)’ involvement: The enrolment period 
corresponds to the 10-day treatment period which is the common duration for Lassa fever 
treatment. The study itself started in August 2021 and is supposed to end in December 2022.  
 

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 5 of 9 
 
Risk(s):  
Favipiravir has never been used for the treatment of Lassa fever in humans but there is evidence 
from laboratory and animal studies suggesting that it is active. Therefore, it is not known 
whether and at which dose it is beneficial for the treatment of Lassa fever. The dose used in this 
study is a dose estimate based on previous studies in humans and in animal models. The most 
frequent side effects of favipiravir are decreased liver function, diarrhoea, decrease of white 
blood cells, decrease of neutrophils, increased blood uric acid and increased blood triglycerides. 
There may also be a temporary effect on the conduction system of the heart. To minimize this 
risk, repeated investigations of the heart will be performed by ECG.  
Administration of ribavirin is standard of care for Lassa fever patients and therefore there is no 
additional risk associated with ribavirin. The most frequent side effects of ribavirin are pain, 
swelling and soreness at the injection site, nausea, flu-like symptoms, tiredness, fever, chills or 
shaking, headache, mood changes, irritability, muscle pain, stomach pain, vomiting and loss of 
appetite.  
The total amount of blood is 124 ml taken over 10 days and does not pose a particular risk for 
your health. The minimal risks of blood drawing are possible discomfort like painful swelling 
of the skin or local infection. Any bleeding can be stopped by putting pressure on the puncture 
site. There might be the risk of infection or, in rare cases, damage of nerves caused by insertion 
of catheters for repeat blood draws, but this risk is also very low. Before the start of the study, 
the personnel will receive trainings in Good Clinical Practice (GCP), research ethics, study 
procedures and blood drawing. The study team will consist of personnel which is trained in 
supportive care of Lassa fever patients. 
 
Modality of providing treatments and action(s) to be taken in case of injury or adverse 
event(s): If you suffer any injury as a result of your participation in this research, you will be 
treated at ISTH and the research will bear the cost of this treatment. There will also be an 
insurance covering all trial related injuries. You will receive the insurance certificate as well as 
the policy. This proceeding will not have any influence on your legal rights.  
 
Costs to the participants, if any, of joining the research: Your participation in this research 
will not cost you anything.  

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 6 of 9 
 
Benefit(s):  
There is benefit to your community anticipated from participation in this research. Benefits to 
the community may be a new and more effective treatment for Lassa fever. This will help to 
better treat Lassa fever in the future. 
 
Confidentiality:  
All data collected in this study will be kept confidential. Information about you that will be 
collected during the research will be put away and no-one, but the researchers, will be able to 
see it. Any information about you and all your samples will have a number on it instead of your 
name (pseudonymized data). Only the researcher will know what your number is and will lock 
that information up with a lock and key. It will not be shared or given to anyone except 
designated persons. As part of our responsibility to conduct this research properly, officials 
from ethics committees, NAFDAC (National Agency for Food and Drug Administration and 
Control) and from the sponsor will have access to the medical records for verification of 
correctness. 
Data from the research will be reported and may be published but will never include your name 
or identify any individual participants when shared with third parties (e.g. regulatory 
authorities, clinical trial registries as Nigeria Clinical Trial Registry or scientific journals).  
 
Due inducement(s): No costs will occur to you regarding your treatment of Lassa Fever 
(hospitalization, examinations, drugs) as long as you participate in the study. The sponsor of 
this research will bear these costs. You will not be paid any fees for participating in this 
research. You will receive one impregnated mosquito net as further incentive for taking part in 
the research.  
 
Consequences of participants’ decision to withdraw from research and procedure for 
orderly termination of participation: You can choose to withdraw from the research at any 
time. This will not affect medical care given to you. If you withdraw from the study, you will 
be asked whether information that has been obtained about you before you chose to withdraw 
may be used for analysis and hence may be included in reports and publications. If you also 

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 7 of 9 
 
withdraw your consent for data processing, all obtained data from you will be excluded from 
further analysis and deleted.  
 
What if new information arises during this research project: Sometimes during the course 
of a research project, new information becomes available about the treatment/the disease that 
is being studied. If this happens, your research doctor will tell you about it and discuss with you 
whether you want to continue in the research project. If you decide to withdraw, your research 
doctor will make arrangements for your regular health care to continue. If you decide to 
continue in the research project you will be asked to sign an updated consent form.  
Also, on receiving new information, your research doctor might consider it to be in your best 
interests to withdraw you from the research project. If this happens, he/she will explain the 
reasons and arrange for your regular health care to continue. 
 
What happens to research participants and communities when the research is over:  
During the course of this research, you will be informed about any information that may affect 
your continued participation or your health. The outcome of the research will be shared with 
the scientific community to improve future management of Lassa fever. You may also request 
to be informed about the outcome of the study at any time. 
  
Statement about sharing of benefits among researchers and whether this includes or 
exclude research participants: This research will not lead to commercial products. 
 
Any apparent or potential conflict of interest: None of the researchers (neither the PI, the 
sponsor, nor ISTH) declare conflict of interest. None of the researchers has any relationship 
that may affect the integrity of any aspect of the research. We are not aware of any other 
information that may cause the researchers not to do their work with fear or favor. 
 
 
 

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 8 of 9 
 
Statement of person obtaining informed consent: 
I have fully explained this research to ____________________________________ and have 
given sufficient information, including about risks and benefits, to make an informed decision. 
DATE: _____________________ SIGNATURE: _______________________________ 
NAME: ________________________________________________________________ 
 
Statement of person giving consent: 
I have read the description of the research or have had it translated into language I understand. 
I have also talked it over with the doctor to my satisfaction. I understand that my participation 
is voluntary. I know enough about the purpose, methods, risks and benefits of the research study 
to judge that I want to take part in it. I understand that I may freely stop being part of this study 
at any time. I have received a copy of this consent form to keep for myself. I have further 
received a copy of the insurance certificate and policy. 
 
DATE: ___________________ SIGNATURE: _________________________________ 
 
NAME: ________________________________________________________________ 
 
 
PARTICIPANT RESEARCH IDENTIFIER 
 
 
 
If illiterate 
A literate witness must sign (if possible, this person should be selected by the participant and 
should have no connection to the research team). Participants who are illiterate should include 
their thumb print as well.  
 
I have witnessed the accurate reading of the consent form to the potential participant, and the 
individual has had the opportunity to ask questions. I confirm that the individual has given 
consent freely.  
 
 
 

IRRUA SPECIALIST TEACHING HOSPITAL 
KM 87, BENIN AUCHI ROAD, P.M.B. 8, IRRUA, EDO STATE, NIGERIA 
Centre of Excellence for the Management and Control of Lassa Fever 
08058065577, 070600483732; irruateachosp@yahoo.com; www.irruaspecialistteachinghospital.com 
NHREC Approval Number: NHREC/01/01/2007-14/09/2021 
Date of NHREC approval: 14/09/2021  
This approval will elapse on: 13/09/2022 
Informed Consent Form_Irrua_SAFARI_v3 
 
10/01/2022 Page 9 of 9 
 
DATE: ____________WITNESS’ SIGNATURE (if applicable):__________________ 
 
WITNESS’ NAME (if applicable): __________________________________________ 
 
 
_______________________________________________________________________ 
 
 
AND 
THUMB-PRINT OF PARTICIPANT 
 
 
 
 
 
 
 
 
Detailed contact information including contact address, telephone, fax, e-mail and any 
other contact information of researcher(s), institutional NHREC and head of the 
institution:  
This research has been approved by the National Health Research Ethics Committee of Nigeria 
(NHREC) and the Chairman of this Committee, Prof. Zubairu Iliyasu, NHREC, can be contacted via 
info@nhrec.net and +234 9 523 8367. This research has also been approved by the Health Research 
Ethics Committee of ISTH and the Chairman of this Committee, Prof. M.A.C. Odike, can be contacted 
at ISTH REC/IEC Irrua, Nigeria. The phone number is +234 815 299 8878.  In addition, if you have any 
question about your participation in this research, you can contact the principal investigator, Dr. Peter 
Akhideno or the co-principal investigator Dr. Cyril Erameh at address: Irrua Specialist Teaching 
Hospital 
(ISTH), 
Km 
87, 
Benin 
Auchi 
Road, 
P.M.B. 
8. 
The 
phone 
number 
is 
+2348037048831/+2348032413382, 
the 
e-mail 
address 
is: 
ehideno@yahoo.co.uk/ 
cyrilerameh@gmail.com 
PLEASE KEEP A COPY OF THE SIGNED INFORMED CONSENT