Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn's disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial

Author(s):  
Stephen Hanauer ◽  
Bernd Liedert ◽  
Sigrid Balser ◽  
Ekkehard Brockstedt ◽  
Viktoria Moschetti ◽  
...  
2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S107-S108
Author(s):  
J Rosh ◽  
D Turner ◽  
A Griffiths ◽  
D Jacobstein ◽  
O Adedokun ◽  
...  

Abstract Background Ustekinumab (UST) is approved for the treatment of adults with moderate to severe Crohn’s disease (CD). The objective of this study was to evaluate the pharmacokinetics (PK), safety, and efficacy of UST in paediatric patients with moderately to severely active CD who had failed treatment with corticosteroids (CS) and/or immunomodulators (IM) and/or anti-tumour necrosis factor (TNF) therapies. Here, we report the safety and efficacy results through Week 16; PK results are reported separately. Methods This was a Phase 1, multicentre, 16-week, double-blind induction dose-ranging study (NCT02968108) in patients aged 2 to <18 years (body weight [BW] ≥10 kg) with a Paediatric CD Activity Index (PCDAI) score >30 and at least an abnormal C-reactive protein >3.0 mg/l or faecal calprotectin >250 µg/g), or ulcerations in the ileum or colon upon ileocolonoscopy despite adequate treatment with CS ± IM ± anti-TNF therapy. Patients were randomised (1:1) and stratified by weight and prior anti-TNF use for induction to one of 2 weight range-based intravenous (IV) doses: 130mg vs. 390 mg if BW ≥40 kg and 3 mg/kg vs. 9 mg/kg if BW <40 kg. At week 8, all patients received a single subcutaneous (SC) UST maintenance dose of 90mg if BW ≥40 kg or 2 mg/kg if BW <40 kg. Results Forty-four patients (59% ≥40kg BW; >90% anti-TNF exposed) were randomised (n = 23 lower dose; n = 21 higher dose) and treated with UST. Baseline characteristics are summarised in Table 1. At week 16, in the lower dose and higher dose groups, 52%/52% achieved clinical response (reduction in PCDAI ≥15) and 22%/29% had clinical remission (PCDAI ≤10), respectively (Table 2). In addition, 32% and 28% of patients showed endoscopic response (reduction in Simple Endoscopic Score for CD of ≥50%), respectively. Through week 16, 73% of patients reported ≥1 adverse event (AE; 82.6% lower dose vs. 62% higher dose); 2 discontinued due to AEs (1 in each group). Serious AEs occurred in 16% of patients (26% lower dose and 5% higher dose, with CD exacerbation being the most frequent (13%/5%, respectively). Infections occurred in 41% of patients (1 was serious, which was intestinal abscess that spontaneously resolved with sequelae). No injection site reactions, opportunistic infections, malignancies, or deaths were reported. No antibodies to UST were observed. Conclusion As early as 3 weeks and through 16 weeks, both the lower and higher doses of UST (IV week 0 and SC at week 8) improved clinical and endoscopic disease activity in this previously treatment-refractory group of children with CD. The safety profile was consistent with that for UST in adults with CD.


The Lancet ◽  
2016 ◽  
Vol 388 (10051) ◽  
pp. 1281-1290 ◽  
Author(s):  
Julián Panés ◽  
Damián García-Olmo ◽  
Gert Van Assche ◽  
Jean Frederic Colombel ◽  
Walter Reinisch ◽  
...  

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S020-S021
Author(s):  
S Vermeire ◽  
W Sandborn ◽  
F Baert ◽  
S Danese ◽  
T Kobayashi ◽  
...  

Abstract Background Vedolizumab (VDZ) is a gut-selective, humanised, monoclonal α 4β 7 integrin antibody for the treatment of patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). VDZ is currently an intravenous (IV) therapy; a subcutaneous (SC) formulation is under development to provide patients with an alternative route of administration for maintenance treatment for UC and CD. Here we present the first data from the phase 3 study of VDZ SC maintenance treatment in CD. Methods VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a randomised, double-blind, placebo (PBO)-controlled phase 3 trial of VDZ SC as maintenance treatment in adults with moderately to severely active CD. Patients (n = 644) received open-label VDZ 300mg IV induction therapy at Weeks 0 and 2. At Week 6, clinical responders (defined as patients with a ≥70-point decrease in CD Activity Index [CDAI] from baseline) were randomly assigned to receive vedolizumab SC (108 mg every 2 weeks [Q2W]), or placebo (Q2W) for up to 52 weeks. The primary endpoint was clinical remission at Week 52 (defined as CDAI score ≤150). Rank-ordered secondary endpoints were enhanced clinical response at Week 52 (a drop of ≥100 in CDAI score), corticosteroid (CS)-free clinical remission at Week 52, and clinical remission at Week 52 in anti-tumour necrosis factor (TNF)-naïve patients. Finally, VDZ immunogenicity and predefined adverse events of special interest were assessed. Results Patients who responded to VDZ IV induction at Week 6 (n = 409) were randomised to VDZ SC (n = 275) or PBO (n = 134) maintenance and received at least 1 dose of study drug; 61% and 53%, respectively, were previously exposed to anti-TNF therapy. At Week 52, 48.0% of patients on VDZ SC vs. 34.3% on PBO were in clinical remission (p = 0.008, Figure). Enhanced clinical response at Week 52 was reached by 52.0% vs. 44.8% of patients on VDZ SC vs. PBO, respectively (p = 0.167). Among patients on concomitant CS at baseline (VDZ SC, n = 95; PBO, n = 44), 45.3% receiving VDZ SC vs. 18.2% receiving PBO achieved CS-free clinical remission at Week 52. Of anti-TNF-naïve patients (VDZ SC, n = 107; PBO, n = 63), 48.6% vs. 42.9% were in clinical remission at Week 52 in the VDZ SC and PBO arms, respectively. Injection-site reactions were reported for <3% of patients treated with VDZ SC. Serious infections, malignancy, and liver injury were ≤5% for both arms. Anti-VDZ antibodies were detected in 7 (2.5%) patients treated with VDZ SC arm; 4 of 7 patients developed neutralising antibodies. No new safety signals were observed. Conclusion Among VDZ IV induction responders, significantly more patients on maintenance VDZ SC than PBO achieved clinical remission at Week 52. The safety findings with VDZ SC remain in line with the known safety profile of VDZ IV in patients with CD.


The Lancet ◽  
2019 ◽  
Vol 393 (10182) ◽  
pp. 1699-1707 ◽  
Author(s):  
Byong Duk Ye ◽  
Marina Pesegova ◽  
Olga Alexeeva ◽  
Marina Osipenko ◽  
Adi Lahat ◽  
...  

2016 ◽  
Vol 150 (4) ◽  
pp. S157-S158 ◽  
Author(s):  
William Sandborn ◽  
Brian G. Feagan ◽  
Christopher Gasink ◽  
Douglas Jacobstein ◽  
Long-Long Gao ◽  
...  

2017 ◽  
Vol 2 (3) ◽  
pp. 154-162 ◽  
Author(s):  
Tadashi Yokoyama ◽  
Akihiko Ohta ◽  
Satoshi Motoya ◽  
Masakazu Takazoe ◽  
Toshitaka Yajima ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document