scholarly journals Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e043666
Author(s):  
Siew Eng Choon ◽  
Mark G Lebwohl ◽  
Slaheddine Marrakchi ◽  
A David Burden ◽  
Tsen-Fang Tsai ◽  
...  
Keyword(s):  
Phase Ii ◽  
Controlled Trial ◽  
Unmet Need ◽  
Intravenous Dose ◽  
Pustular Psoriasis ◽  
Controlled Study ◽  
Supplementary File ◽  
Physician Global Assessment ◽  
Double Blind ◽  
Generalized Pustular Psoriasis

IntroductionGeneralized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare.Methods and analysisAt least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.Ethics and disseminationThe study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation’s Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.Trial registration detailsClinicalTrials.gov identifier: NCT03782792; Pre-results.

A randomized, double-blind, placebo-controlled trial for prevention of oxaliplatin-induced neuropathy symptoms with pregabalin.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 553-553
Author(s):  
M. Karthaus ◽  
C. S. Karapetis ◽  
M. Brown ◽  
N. Pavlakis ◽  
T. Trarbach ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Interim Analysis ◽  
Controlled Trial ◽  
Unmet Need ◽  
Persistent Pain ◽  
Controlled Study ◽  
Double Blind ◽  
Treatment Groups ◽  
Persistent Symptoms

553 Background: Sensorial peripheral neuropathy (PNP) is a major limitation for pts receiving oxaliplatin-based ctx for CRC. Pregabalin is widely used for treatment of oxaliplatin-induced PNP. We evaluated the efficacy of pregabalin vs. placebo for the prevention of paresthesia from the onset of oxaliplatin-based ctx over each cycle. Methods: Rd, db, placebo-controlled study in adult CRC pts with ECOG 0-2 to undergo a new oxaliplatin/5-FU/FA-based ctx. Pts were excluded if they had neuropathic pain or other of painful paresthesia prior to baseline. Paresthesia, dysesthesia, and pain were rated on a numerical scale (NRS 0-10) every day. Primary endpoint was the time of onset of persistent symptoms (NRS >4). Results: Of the 69 screened pts, 64 were randomized and 61 received study medication (32 pregabalin vs. 29 placebo). Pts were balanced in both arms regarding age, sex, stage, and ctx. There were no differences between both treatment groups for all PNP parameters at any cycle. One pt in both arms developed paresthesia (5.3%) after 9 cycles of ctx, 1 pt had persistent pain (placebo arm). During the follow-up period persistent paresthesic, dysesthesic, and persistent pain developed in 2 vs. 1, 2 vs. 2, and 0 vs. 2 pts, respectively. The study was terminated after a blinded data review found that there were very few events of persistent symptoms, which was then confirmed an interim analysis. Nausea and anorexia were the most frequently reported AE in both groups. Conclusions: The results of this study, which was terminated early at interim analysis, is that too few patients developed persistent symptoms to allow any meaningful treatment difference for prevention of neuropathic pain related to oxaliplatin by pregabalin. There remains an unmet need for oxaliplatin-induced PNP with new trial design issues in this field urgently needed. No significant financial relationships to disclose.

ISA247: Quality of Life Results from a Phase II, Randomized, Placebo-Controlled Study

2008 ◽  
Vol 12 (6) ◽  
pp. 268-275 ◽  
Author(s):  
Aditya K. Gupta ◽  
Richard G. Langley ◽  
Charles Lynde ◽  
Kirk Barber ◽  
Wayne Gulliver ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Phase Ii ◽  
Life Quality ◽  
Skin Condition ◽  
Controlled Study ◽  
Double Blind ◽  
Plaque Type ◽  
Psoriasis Disability Index ◽  
Stable Plaque

Background: Psoriasis is a chronic skin condition that can negatively affect a patient's quality of life (QoL), often hindering social functioning. ISA247, a novel psoriatic agent, has shown clinical efficacy in moderate to severe psoriasis sufferers, but its effect on QoL is currently not reported. Objective: The objective of this study was to assess the effect of ISA247 on the QoL in patients with stable, plaque-type psoriasis. Methods: A phase II, randomized, double-blind, placebo-controlled, parallel-group, multicenter study assessed the effects of ISA247 doses of 0.5 mg/kg/d ( n = 77) or 1.5 mg/kg/d ( n = 83) compared with placebo ( n = 41) for 12 weeks. QoL was assessed using the Dermatology Life Quality Index (DLQI) and Psoriasis Disability Index (PDI) scales. Results: ISA247 treatment (pooled groups) significantly improved QoL scores as assessed by both the DLQI and the PDI compared with those receiving placebo ( p < .05). Treatment with the higher dose of 1.5 mg/kg/d demonstrated a significantly greater response to many of the QoL scales compared with the 0.5 mg/kg/d group ( p < .05). Conclusions: ISA247 appears to improve the QoL while also providing effective treatment for chronic, moderate to severe, plaque-type psoriasis.

scholarly journals Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)

2017 ◽  
Vol 77 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Dinesh Khanna ◽  
Christopher P Denton ◽  
Celia J F Lin ◽  
Jacob M van Laar ◽  
Tracy M Frech ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Controlled Trial ◽  
Safety Data ◽  
Open Label ◽  
Double Blind ◽  
Skin Score ◽  
Open Label Extension ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesAssess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.MethodsPatients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.ResultsOverall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.ConclusionsSkin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.Trial registration numberNCT01532869; Results.

Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial

Perfusion ◽  
2017 ◽  
Vol 32 (7) ◽  
pp. 591-597 ◽  
Author(s):  
Geoff G. Lockwood ◽  
Leilani Cabreros ◽  
Dorota Banach ◽  
Prakash P. Punjabi
Keyword(s):  
Cardiac Surgery ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Morphine Consumption ◽  
Controlled Study ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Subcutaneous Infusion ◽  
Randomised Controlled Study ◽  
Randomised Controlled

Background: Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Method: Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg-1.hr-1) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. Results: There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l-1. There were no adverse events as a consequence of the study. Conclusion: Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. Clinical trial registration: ISRCTN13424423 ( https://www.isrctn.com )

Dose-Finding of Linaclotide for Patients with Chronic Constipation in Japan: A Phase II Randomized, Double-Blind, and Placebo-Controlled Study

2017 ◽  
Vol 152 (5) ◽  
pp. S515-S516
Author(s):  
Shin Fukudo ◽  
Hiroto Miwa ◽  
Atsushi Nakajima ◽  
Yoshikazu Kinoshita ◽  
Masanori Kosako ◽  
...  
Keyword(s):  
Phase Ii ◽  
Chronic Constipation ◽  
Dose Finding ◽  
Controlled Study ◽  
Double Blind
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