JIKI Trial In Guinea
Reaction Project
Daouda Sissoko, on behalf of JIKI group
Center for tropical medicine and clinical international
health, University Hospital Center, Bordeaux
INSERM 897, University of Bordeaux, France
INSERM Guinea/ National Task Force against Ebola
No conflict of interest to declare
Evaluation of efficacy and antiviral activity
of favipiravir in non-human primates &
humans
JIKI Trial
JIKI Trial preparation and progress
Number of cases and deaths among
confirmed cases in Guinea
Start of JIKI trial
Prop. de cas confirmés décédés (%)
Source: Ebola in Guinea, Daily Sitrep. 5 may 2015 (5 may 2015). Guinean MoH and WHO
*Documentation non-exhaustive des décès communautaires non-prélevés
Methods
– Settings: 4 Ebola treatment centers in Guinea
– Sponsor/funding: Inserm/EU Horizon 2020
•
Objective: to assess the efficacy of high-dose favipiravir in decreasing mortality
in humans with EVD
•
Design: non-comparative, open-label, phase II trial
•
Inclusion criteria: Age >1 year, able to take pills, positive EBOV test, informed
consent,
•
Treatment: Favipiravir, Toyama Chemical Co., Ltd (oral tablets 200 mg), 10 days
(Mentre et al., Lancet Infect Dis 2014, Frange et al., Lancet 2015)
•
Primary outcome: Mortality at Day 14
•
Secondary outcomes: Evolution of EBOV plasma RNA and infectious loads,
grade 3-4 adverse events, resistance mutations, trough concentrations of
favipiravir
•
Analysis: Reference = pre-trial mortality (MSF/EMLab database, Sept 15- Dec
14, 2015), with same team, same procedures and same laboratory
• Funding:
Settings and teams
– EEUU
– Inserm
• Partners:
Inserm, MSF,
EuroMobLA,
ALIMA, Pasteur,
French Red
Cross, B-FAST,
French Army
Health Service
Settings: 4 Ebola Treatment Centers :
• 3 in the southern Guinean Highlands
(Gueckedou, Nzerekore, Macenta),
• 1 in costal Guinea (Conakry)
JIKI trial
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Flow chart
7
There is no child between 7 and 12 years included in the trial.
RT-PCR CT values at baseline and during
follow-up
First 69 adult participants, JIKI trial, 17 DEC 2014 – 20 JAN 2015
“cycle threshold”(Ct)
value is inversely
proportional to viral
load Ct=20
equivalent to 108
copies/ml; +3 cycles
equivalent to -1 log
Baseline Ct value
<20
>20
% with negative RT-PCR
At Day-2 of treatment
At Day-4 of treatment
0 (0%) 11 (28%)
1 (4%) 20 (51%)
Median gain in Ct
Day 2 – Baseline
Day 4 – Baseline
+ 1.5
+ 2.9
+ 5.2
+ 12.3
Report : Favipiravir in patients with Ebola Virus Disease: early results of the JIKI
trial in Guinea. D. SISSOKO, et al. CROI 2015, Feb. 25, Seattle, USA, Abstr 103ALB
JIKI trial
(oral presentation)
Outcome by baseline serum creatinine
and RT-PCR Ct value
First 69 adult participants, JIKI trial, 17 DEC 2014 – 20 JAN 2015
Creatinine at baseline***
R=0.44.
P=0.0005
Outcome
= Death
n
(column %)
n
5
10
12
(19%)
(37%)
(44%)
3
81% 10
12
(60%)
(100%) 100%
(100%)
19
10
4
(58%)
(30%)
(12%)
3
0
42% 1
(16%)
(0%)
(25%)
(row %)
Baseline Ct <20
<110 μM
110-299 μM
>300 μM
Baseline Ct >20
<110 μM
110-299 μM
>300 μM
7%
*** 9 missing values
Composite indicator Creat, CK and AST
Sissoko et coll., CROI,
February 23-26 2015, 103-ALB
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Comments
•
RT-PCR Ct value and serum creatinine are two excellent markers of disease
severity :
–
–
–
–
50% of patients showed up with a Ct value < 20 (equivalent to 108 copies/ml)
52% of patients showed up with AKI
81% of patients with baseline Ct < 20 had persistent AKI; 100% died
42% of patients with baseline Ct > 20 had transient AKI; 97% recovered
•
Final analyses stratified by baseline CT values
•
Feasability of use, tolerability, safety, prospective standardized clinical, virology
and biomarker data collection
• Further PK analysis undergoing to optimize the dosing
Concentrations measurements and link with viral load decrease and survival
•
Final results over 200 (126 trial, 98 therapeutic cohort) patients to be produced
(data under reviewing, october 2015)
Sissoko et coll. CROI, February 23-26 2015, 103-ALB
JIKI trial
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Conclusions/ Perspectives
• Emergency trials are feasible in the context of a
deadly contagious disease outbreak
• Efficay in patients with Ct≥20 (VL ≤ 7.7 log10
cp/ml) to be comforted by further studies
(higher doses in RCT)
• Ongoing substudy: Clearance of semen among
survivors
• Development of strong partnership with other
European/West African teams (BNI/PHE, NGO,
etc): cross-fertilization
Acknowledgements
Special thanks to:
• All patients who accepted to participate in the study
• Scientific Advisory Board: L Abel, G Carson, G Davies, A Diallo, P Frange, B Godard, A Kelly, F Le Marcis, N Morgensztejn,
A Ndjeyi Mbiguino, VK Nguyen, C Semaille, AM Taburet, JM Treluyer, Y Yazdanpanah
• Data Safety Monitoring Board: D Baush, B Bazin, E Bottieau, A Faye, R Garraffo, R Porcher, P Redfield
• Sponsor (Inserm): T Damerval, JF Delfraissy, Y Levy, C Levy-Marchal,
• Ethics Committees of Inserm (CEEI/IRB), MSF (MSF ERB), and Republic of Guinea (CNERS)
• Toyama Chemical Co., Ltd, for the donation of favipiravir: H Kitaguchi, K Yamada
The JIKI study group is constituted as follows:
– Guinea Ebola Task Force: S Keita
– Centre de Formation et de Recherche en Santé Rurale de Maferinyah: AH Beavogui
– MSF: I Arnould, A Antierens, N Bangoura, E Berbain, D Camara, FS Camara, S Carazo, AM Camara, L Delamou, B
Draguez, E Folkeson, MC Lamah, A Lefevre, T Leno, M Loua, K Malme, E Manfrin, A Maomou, S Ombelet, P Piguet,
M Poncin, OO Sakovogui, AY Sidiboun, A Tounkara, M Van Herp, D van Hoeydonck, I Verreckt
– ALIMA: B Abdoul, A Augier, G Baret, TS Barry, S Berrette, A Bongono, C Camara, M Conde, I Defourny, JM Dindart,
R Doumbouya, G Leduc, M Loua, R Lolamou FR Koundouno, S Harouna, V Massala, A Moumouni, P Mumbere, JP
Olele, R Palich, F Petitjean, O Peyrouset, C Provost, S Shepherd, C Sekou, A Soumah
– Croix Rouge Française: G Colin, D Dougo, P Gorovogui, E Olivier, Y Ruaux, B Simon, T Tran Minh, FT Simpogui
– Inserm: X Anglaret, M Cervantes-Gonzalez, S Eholie, X de Lamballerie, C Laouenan, D Malvy, F Mentre, R Moh, B
Murgue, C Nchot, L Nguessan, B Siloue, D Sissoko
– P4 Lyon Mérieux: S Baize, H Raoul
– EMLab: J Akoi Bore, M Carroll, S Diederich, S Duraffour, J Hinzmann, RF Koundouno, A Kraus, B Liedigk, P Maes, D
Ngabo, M Rudolf, R Thorn
– BFAST: Y Deccache, C Dumont, JF Durant JL Gala, L Irenge, B Smiths, N Toufic, S Van CauwenbergheSSA: H
Dampierre, V Foissaud, F Janvier, C Rapp, H Savini
– ADERA: O Fouassier, J Rivenc
– Solthis: A Abadie, R Benhamou, E Dortenzio, PE Martineau, L Pizarro
CROI, February 23-26 2015
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JIKI trial
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