scholarly journals OP27 Long-term safety and efficacy of risankizumab treatment in patients with Crohn’s disease: Final results from the Phase 2 open-label extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S024-S025 ◽  
Author(s):  
M Ferrante ◽  
B G Feagan ◽  
J Panés ◽  
F Baert ◽  
E Louis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Opportunistic Infections ◽  
Activity Index ◽  
Induction Treatment ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Efficacy and safety of the IL-23 inhibitor risankizumab (RZB) have been assessed in patients with moderate-to-severe Crohn’s disease (CD) following induction/maintenance treatment.1,2 Responders to RZB in a Phase 2 induction/maintenance study2,3 could enrol in an open-label extension (OLE), NCT02513459.4 Final safety and efficacy results from this RZB OLE study are reported here. Methods Patients achieving clinical response (CResp) (decrease from baseline [BL] in CD Activity Index [CDAI] ≥100) without remission (CRem) (CDAI <150) after Period 2 (Week 26) or CResp/CRem after Period 3 (Week 52) of the preceding study1 received open-label 180 mg subcutaneous (SC) RZB every 8 weeks (Q8W) for up to 206 weeks. Patients who lost CResp/CRem at screening of the OLE were re-induced with open-label 600 mg IV RZB at Weeks 0, 4, and 8. Patients receiving re-induction treatment only received subsequent 180 mg SC RZB Q8W if they regained CResp/CRem following re-induction. A centrally read ileocolonoscopy was performed yearly. Treatment-emergent adverse events (AEs) were collected up to 20 weeks after the last RZB dose. CRem and endoscopic remission (ER [CD Endoscopic Index of Severity (CDEIS) ≤4 or CDEIS ≤2 for patients with isolated ileitis at BL]) were reported up to Week 152. Non-responder imputation (NRI) and observed case analysis were used for binary endpoints. Results Sixty-five patients with CD were enrolled in the OLE, with 4 patients re-induced. At BL of the preceding study, median (range) age was 34 (19–67) years and median (range) disease duration was 10 (2–38) years. Sixty patients (92%) were previously exposed to TNF antagonists. In the OLE, median (range) exposure to RZB was 1014.0 (114–1317) days. Twenty-one (32%) patients prematurely discontinued RZB, including 6 (9%) who had developed an AE. AEs were reported in 60 (92%) patients; 23 (35%) experienced serious AEs. The most common AEs were nasopharyngitis (31%), gastroenteritis (23%), and fatigue (20%). Serious infections were reported in 6 (9%) patients and opportunistic infections in 3 (5%) patients. No tuberculosis, malignancies, or deaths occurred. At Week 0 of the current study, 47 (72%) patients were in CRem and 27 (42%) patients had ER. Both CRem and ER were sustained up to Week 152 (Table). Conclusion In this final analysis of patients with CD receiving long-term open-label RZB treatment, the safety profile of RZB remained consistent with previous data² with no new safety signals. Clinical and endoscopic remissions were sustained. References

Tu1873 LONG-TERM SAFETY AND EFFICACY OF RISANKIZUMAB TREATMENT IN PATIENTS WITH CROHN'S DISEASE: FINAL RESULTS FROM THE PHASE 2 OPEN-LABEL EXTENSION STUDY

2020 ◽  
Vol 158 (6) ◽  
pp. S-1198
Author(s):  
Marc Ferrante ◽  
Brian G. Feagan ◽  
Julian Panes ◽  
Filip J. Baert ◽  
Edouard Louis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extension Study ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

DOP71 Efficacy, safety, and tolerability of ustekinumab in paediatric patients with moderately to severely active Crohn’s disease: Results from, UniStar, a phase 1 study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S107-S108
Author(s):  
J Rosh ◽  
D Turner ◽  
A Griffiths ◽  
D Jacobstein ◽  
O Adedokun ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Opportunistic Infections ◽  
Activity Index ◽  
Phase 1 ◽  
Double Blind ◽  
Faecal Calprotectin ◽  
Adequate Treatment ◽  
Safety And Efficacy ◽  
Paediatric Patients

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.

scholarly journals P219 Long-term safety of filgotinib in patients with PsA: week 52 safety data from a Phase 2 open-label extension study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Laura Coates ◽  
Philip Mease ◽  
Dafna Gladman ◽  
Filip Van den Bosch ◽  
Anna Rychlewska-Hanczewska ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

Safety and efficacy of maintenance infliximab therapy for moderate-to-severe Crohn’s disease in children: REACH open-label extension

2011 ◽  
Vol 27 (3) ◽  
pp. 651-662 ◽  
Author(s):  
Jeffrey Hyams ◽  
Thomas D. Walters ◽  
Wallace Crandall ◽  
Subra Kugathasan ◽  
Anne Griffiths ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Infliximab Therapy ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

scholarly journals POS0315 LONG-TERM SAFETY AND EFFICACY OF LENABASUM DURING 3 YEARS IN AN OPEN-LABEL EXTENSION (OLE) OF A PHASE 2 STUDY OF LENABASUM IN REFRACTORY SKIN DISEASE IN DERMATOMYOSITIS (DM)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 383.1-384
Author(s):  
V Werth ◽  
J. Concha ◽  
J. Burroughs ◽  
J. Okawa ◽  
R. Feng ◽  
...  
Keyword(s):  
Activity Score ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Phase 2 Trial ◽  
Phase 2 Study ◽  
Patient Reported ◽  
Open Label Extension ◽  
To Receive

Background:Lenabasum is a synthetic, non-immunosuppressive, selective cannabinoid receptor type 2 agonist that activates resolution of inflammation. Lenabasum had acceptable safety and tolerability and improved efficacy outcomes in the initial 16-week double-blinded, randomized, placebo-controlled Part A of Phase 2 trial JBT101-DM-001 (NCT02466243) in DM subjects with refractory skin involvement. In that study, lenabasum or placebo was added to stable background treatment, with immunosuppressive therapies allowed.Objectives:To assess long-term safety and efficacy in DM subjects in this study.Methods:Subjects who completed Part A of the Phase 2 study (n = 22) were eligible to receive oral lenabasum 20 mg BID in an open-label extension (OLE) that assessed safety and efficacy at 4 weeks, then every 8 weeks.Results:20/22 (91%) eligible subjects enrolled in the OLE, following a mean interval of 31 weeks from the end of Part A, during which they continued to receive standard-of care treatments, to the start of the OLE during which lenabasum 20 mg BID was added. 17/20 (85%) subjects were on stable baseline immunosuppressive drugs. At the time of this data cut-off, 17 subjects were still enrolled, 17 had completed 140 months (2.7 years), and 15 had completed 156 months (3 years) of OLE dosing.All OLE subjects experienced at least 1 adverse event (AE), with 118 AEs during the OLE through Dec 2020. Most AEs were mild (n = 111, 94%), with 2 severe AEs (fatigue and metastatic prostate cancer) considered unrelated to lenabasum. AEs occurring in ≥ 3/20 OLE subjects were: URI (n = 5); fatigue (n = 4); nausea (n = 3); common cold (n = 3); UTI (n = 3); and DM flare (n = 3). No serious AEs related to lenabasum have been reported in this OLE to date. No subject discontinued the OLE because of an AE related to lenabasum.Improvement was seen in multiple physician- and patient-reported efficacy outcomes. CDASI activity score improved through the first 15 months of lenabasum treatment in the OLE and remained stable thereafter, with an improvement of ~20 points from the beginning of the study maintained from Month 15 through Year 3 in the OLE. CDASI damage score increased through the first year of the OLE, even though skin activity was decreasing, but lessened thereafter, returning after 3 years to about the same level it was at the beginning of the OLE. Other outcomes shown in Figure 1 followed the same general pattern as CDASI activity score, with improvement through the first 12-16 months of the OLE, then stability thereafter. Of note, 2 subjects had disease flares shortly after stopping lenabasum for conclusion of the OLE.Conclusion:Lenabasum continues to have a favorable safety and tolerability profile in the OLE of the Phase 2 trial JBT101-DM-001 with no serious AEs or study discontinuations related to lenabasum. The CDASI activity score and multiple other physician and patient-reported outcomes improved and have remained stable, showing durability of improvement in these patients with refractory skin disease. Skin damage was reversible and began to improve once skin activity stabilized. The limitations of attributing this improvement to lenabasum in the setting of open-label dosing is acknowledged. These data support further testing of lenabasum for the treatment of DM, and a Phase 3 study of lenabasum in DM is ongoing.Figure 1.Change from Baseline in Selected Efficacy Outcomes in OLE of Phase 2 Trial JBT101-DM-001Disclosure of Interests:Victoria Werth Grant/research support from: Investigator for Corbus Pharmaceuticals and received funding to conduct trials, Josef Concha: None declared, Julie Burroughs: None declared, Joyce Okawa: None declared, Rui Feng: None declared, Anisha Jobanputra: None declared, Robert Borucki: None declared, Kathleen Hally Employee of: Employee of Corbus Pharmaceuticals, Emily Hejazi: None declared, Michael Tillinger Employee of: Employee of Corbus Pharmaceuticals, Scott Constantine Employee of: Employee of Corbus Pharmaceuticals, Nancy Dgetluck Employee of: Employee of Corbus Pharmaceuticals, Barbara White Employee of: Employee and stockholder of Corbus Pharmaceuticals

scholarly journals OP031 Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2 open-label 48-week extension study

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S18-S19
Author(s):  
J. Panés ◽  
G.R. D'Haens ◽  
P.D.R. Higgins ◽  
L. Mele ◽  
M. Moscariello ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extension Study ◽  
Phase 2 ◽  
Open Label
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