- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
LBP12
Efficacy and safety results of the phase 2 JNJ-56136379 JADE study
in patients with chronic hepatitis B: Interim week 24 data
Harry Janssen1, Jinlin Hou2, Tarik Asselah3, Henry Chan4,
Fabien Zoulim5, Yasuhito Tanaka6, Ewa Janczewska7, Ronald Nahass8,
Stefan Bourgeois9, Maria Buti10, Pietro Lampertico11, Oliver Lenz12,
Thierry Verbinnen12, Joris J. Vandenbossche12, Willem Talloen12,
Michael Biermer12, Ronald Kalmeijer13, Maria Beumont-Mauviel13,
Umesh Shukla13. 1Toronto General Hospital, Toronto, Canada; 2Nanfang
Hospital, Southern Medical University, Guangzhou, China; 3University
Paris Diderot, INSERM UMR1149, Hôpital Beaujon, Clichy, France; 4The
Chinese University of Hong Kong, Hong Kong SAR, China; 5Hospices Civils
de Lyon and Lyon University & INSERM U1052-Cancer Research Institute
of Lyon, Lyon, France; 6Nagoya City University Graduate School of
Medical Sciences, Nagoya; 7University of Silesia, School of Health
Sciences in Bytom, Medical University of Silesia, Silesia, Poland; 8ID Care,
Hillsborough, United States; 9ZNA Jan Palfijn, CPU, Antwerp, Belgium;
10Hospital Universitario Vall d’Hebrón and CIBERHED del Instituto
Carlos III, Barcelona; 11CRC “A. M. and A. Migliavacca” Center for Liver
Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS
Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di
Milano, Milan, Italy; 12Janssen Pharmaceutica NV, Beerse, Belgium;
13Janssen Pharmaceuticals R&D, Titusville, United States
Email: [email protected].
Background and aims: JNJ-56136379 (JNJ-6379) is a potent capsid
assembly modulator producing normal empty capsids (CAM-N). We
present wk 24 efficacy and safety from the ongoing Ph2 JADE study
(NCT03361956) in chronic hepatitis (CHB) patients ( pts).
Method: CHB not treated at study start (NT) and virologically
suppressed (VS) HBeAg+ or HBeAg− pts were randomized to 75/
250 mg JNJ-6379 qd or placebo (pbo) with a nucleos(t)ide analogue
(NA; TDF/ETV) or received JNJ-6379 alone. As JNJ-6379 monotherapy
will not be developed further, data from the combination arms are
presented here. Primary endpoint was change from baseline (BL) in
HBsAg at wk 24.
Results: Of 172 pts in the combination arms (88 NT; 84 VS), 48%were
Asian and 34% HBeAg+.
In NT HBeAg+ pts, a more pronounced mean (SE) DNA decline fromBL
at wk 24 was observed for JNJ-6379 75 mg and 250 mg + NA [5.53
(0.23) and 5.88 (0.34) log10 IU/mL] over NA+pbo [5.21 (0.42)]; HBV
DNAwas <LLOQ in 0/12, 4/11 (36%) and 1/8 (13%) pts, respectively.
At wk 24 in NT HBeAg±pts, JNJ-6379 75 mg and 250 mg + NA showed
an increased mean (SE) HBV RNA decline from BL [2.82 (0.25) and
3.13 (0.35) cp/mL] over NA+pbo [1.43 (0.32)]. HBV RNAwas target not
detected (TND) at wk 24 in 16/27 (59%), 19/25 (76%) and 9/20 (45%)
NT HBeAg+/− pts, respectively. All JNJ-6379 VS pts with detectable
HBV RNA at BL achieved HBV RNA TND at wk 24 vs 0% with NA+pbo.
JNJ-6379 250 mg+NA showed a mean (SE) HBsAg decline of 0.40
(0.15) log10 IU/mL in NT HBeAg+ pts at wk 24 (Figure). Pts with HBsAg
decline also had HBeAg and HBcrAg declines and frequently early on
treatment isolated ALT flares.
Maximal JNJ-6379+NA individual HBsAg and HBeAg reductions were
1.28 and 1.8 log10 IU/mL, respectively. Proportions of JNJ-6379+NA NT
HBeAg+ pts with >0.3 log10 IU/mL reductions from BL in HBsAg and
HBeAgwere 8/23 (35%) and 19/23 (83%) vs 1/8 (13%) and 4/8 (50%)NA
+pbo, respectively. Proportions of VS JNJ-6379+NA HBeAg+ pts with
>0.3 log10 IU/mL reductions in HBeAgwere 6/19 (32%) vs 1/5 (20%) NA
+pbo.
No study treatment related serious adverse events or clinically
significant changes in laboratory parameters occurred.
Conclusion: In not treated pts, JNJ-6379+NA increased HBV DNA
suppression over NA alone. A mean 0.4 log10 IU/mL HBsAg decline
with JNJ-6379 250 mg+NAwas seen in NT HBeAg+ pts. JNJ-6379+NA
was safe and well tolerated, supporting evaluation of JNJ-6379 in
combination with an NA and the siRNA JNJ-73763989 in the ongoing
Ph2 REEF-1 study (NCT03982186). |
|