Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Phase 1 study on the safety and efficacy of E6011, antifractalkine antibody, in patients with Crohn's disease.

ABSTRACT:

Background and aim

E6011 is a humanized monoclonal antibody targeting fractalkine (FKN), a CX3C chemokine, which regulates leukocyte trafficking during inflammation. We evaluated the safety and pharmacokinetic profile of E6011 in patients with Crohn's disease (CD) and also performed preliminary pharmacodynamic (PD) and efficacy assessments.

Methods

This study included a 12-week multiple ascending dose (MAD) phase (2, 5, 10, and 15 mg/kg intravenously every 2 weeks, n = 6, 8, 7, and 7, respectively) and a 40-week Extension phase (n = 12) at the same dose as the MAD phase. Serum E6011, serum total FKN (free soluble FKN and E6011-FKN complex) as a PD marker and CD activity index were evaluated. The primary outcome was safety assessment in the MAD phase.

Results

Twenty-seven (96%) of 28 patients had previously been treated with anti-tumor necrosis factor α agents. During the MAD phase, adverse events (AEs) occurred in 18 (64%). The most common AE was nasopharyngitis (five patients, 18%). No severe AEs occurred. Serious AEs occurred in three patients, progression of CD in two, and anemia in one. Serum E6011 concentrations increased dose-dependently after infusion and reached a plateau around 4-6 weeks. Serum total FKN rose simultaneously. Five (18%) patients developed anti-E6011 antibodies during the study. Overall, clinical response and clinical remission were observed at Week 12 in 40% (10/25) and 16% (4/25) of active CD patients, respectively.

Conclusion

E6011 was well-tolerated and might be effective in CD patients. These findings need to be clarified in a randomized controlled study.

SUBMITTER: Matsuoka K

PROVIDER: S-EPMC8451784 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Efficacy and safety of ustekinumab treatment in patients with Crohn's disease

Project description:UNITI-2 was a phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT01369342) comparing the effects (both positive and negative) of an initial treatment with ustekinumab to a placebo over 8 weeks in patients with moderately to severely active Crohn's disease.

2022-09-08 | GSE207022 | GEO

Efficacy and safety of ustekinumab treatment in patients with Crohn's disease

Project description:Efficacy and safety of ustekinumab treatment in patients with Crohn's disease

| PRJNA853329 | ENA

Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study.

Project description:Background and aimsThe objective was to evaluate the pharmacokinetics, safety/tolerability, and efficacy of ustekinumab in children with moderately to severely active Crohn's disease.MethodsIn this Phase 1, multicentre, 16-week, double-blind, induction dose-ranging study [NCT02968108], patients aged 2-<18 years [body weight ≥10 kg] were randomised [1:1] to one of two weight range-based intravenous induction doses: 130 mg vs 390 mg in patients ≥40kg and 3 mg/kg vs 9 mg/kg in patients <40kg. At Week 8, all patients received a single subcutaneous ustekinumab maintenance dose of 90 mg in patients ≥40kg or 2 mg/kg in patients <40kg.ResultsA total of 44 patients were randomised and treated with ustekinumab [n = 23 lower dose; n = 21 higher dose]; median [interquartile range] age was 13.0 [12-16] years. Pharmacokinetics were similar to those in adults with Crohn's disease. However, serum ustekinumab concentrations were lower among those with body weight <40 kg compared with patients ≥40 kg and the reference Phase 3 adult population. Through Week 16, 73% of patients reported ≥1 adverse event [82.6% lower vs 62% higher dose]; two discontinued due to adverse events [one in each group]. Serious adverse events occurred in 16% [26% lower, 5% higher dose], with Crohn's disease exacerbation being the most frequent. At Week 16, 22%/29% [lower/higher dose] achieved clinical remission [Paediatric Crohn's Disease Activity Index ≤10].ConclusionsThe pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn's disease. These results suggest a different dosing regimen may be required for patients <40 kg from that employed in this study; additional pharmacokinetic analyses may be needed in this population.

| S-EPMC8575045 | biostudies-literature

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study.

Project description:Background and aimsRisankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn's disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study.MethodsEnrolled patients had achieved clinical response [decrease in Crohn's Disease Activity Index from baseline ≥100] without clinical remission [Crohn's Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks.ResultsSixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [>71%] and endoscopic remission [>42%].ConclusionsLong-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn's disease, with no new safety signals. Clinical trial registration number: NCT02513459.

| S-EPMC8684487 | biostudies-literature

Pharmacokinetics, Safety and Efficacy of Intravenous Vedolizumab in Paediatric Patients with Ulcerative Colitis or Crohn's Disease: Results from the Phase 2 HUBBLE Study.

Project description:Background and aimsTo date, there are no systematic pharmacokinetic [PK] data on vedolizumab in paediatric inflammatory bowel disease [IBD]. We report results from HUBBLE, a dose-ranging, phase 2 trial evaluating the PK, safety and efficacy of intravenous vedolizumab for paediatric IBD.MethodsEnrolled patients [aged 2-17 years] with moderate to severe ulcerative colitis [UC] or Crohn's disease [CD] and body weight ≥10 kg were randomized by weight to receive low- or high-dose vedolizumab [≥30 kg, 150 or 300 mg; <30 kg, 100 or 200 mg] on Day 1 and Weeks 2, 6 and 14. Week 14 assessments included PK, clinical response and exposure-response relationship. Safety and immunogenicity were assessed.ResultsRandomized patients weighing ≥30 kg [UC, n = 25; CD, n = 24] and <30 kg [UC, n = 19; CD, n = 21] had a baseline mean [standard deviation] age of 13.5 [2.5] and 7.6 [3.2] years, respectively. In almost all indication and weight groups, area under the concentration curve and average concentration increased ~2-fold from low to high dose; the trough concentration was higher in each high-dose arm compared with the low-dose arms. At Week 14, clinical response occurred in 40.0-69.2% of patients with UC and 33.3-63.6% with CD in both weight groups. Clinical responders with UC generally had higher trough concentration vs non-responders, while this trend was not observed in CD. Fourteen per cent [12/88] of patients had treatment-related adverse events and 6.8% [6/88] had anti-drug antibodies.ConclusionsVedolizumab exposure increased in an approximate dose-proportional manner. No clear dose-response relationship was observed in this limited cohort. No new safety signals were identified.

| S-EPMC9426668 | biostudies-literature

Efficacy and Safety of Oral Budesonide in Patients with Active Crohn's Disease in Japan: A Multicenter, Double-Blind, Randomized, Parallel-Group Phase 3 Study.

Project description:BackgroundUS and European guidelines recommend budesonide for the treatment of mild-to-moderate active ileocolic Crohn's disease (CD). However, budesonide has not been approved, and mesalazine is widely used as first-line treatment in Japan. The objective of this study was to evaluate the efficacy and safety of budesonide in patients with mild-to-moderate active CD in Japan.MethodsIn this phase 3 noninferiority study (NCT01514240), 112 patients with a baseline Crohn's Disease Activity Index (CDAI) score of 180-400 were randomized to budesonide or mesalazine for 8 weeks. Assessments included remission rate (CDAI score ≤150) at weeks 2, 4, and 8, change in CDAI score, health-related quality of life (measured using the Inflammatory Bowel Disease Questionnaire [IBDQ]), and tolerability.ResultsThe remission rate at week 8 was numerically higher in the budesonide group (30.4%) than in the mesalazine group (25.0%), and the noninferiority of budesonide to mesalazine was shown. The mean total CDAI score decreased to a greater extent with budesonide than with mesalazine. Mean IBDQ scores improved from baseline to weeks 2, 4, 8, and 10 in both groups; improvements were numerically higher with budesonide than with mesalazine. No safety concerns were found.ConclusionBudesonide is comparably effective to mesalazine in the treatment of Japanese patients with mild-to-moderate active CD.

| S-EPMC5988115 | biostudies-literature

Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.

Project description:BackgroundIMAgINE 1 assessed 52-week efficacy and safety of adalimumab in children with moderate to severe Crohn's disease. Long-term efficacy and safety of adalimumab for patients who entered the IMAgINE 2 extension are reported.MethodsPatients who completed IMAgINE 1 could enroll in IMAgINE 2. Endpoints assessed from weeks 0 to 240 of IMAgINE 2 were Pediatric Crohn's Disease Activity Index remission (Pediatric Crohn's Disease Activity Index ≤ 10) and response (Pediatric Crohn's Disease Activity Index decrease ≥15 from IMAgINE 1 baseline) using observed analysis and hybrid nonresponder imputation (hNRI). For hNRI, discontinued patients were imputed as failures unless they transitioned to commercial adalimumab (with study site closure) or adult care, where last observation was carried forward. Corticosteroid-free remission in patients receiving corticosteroids at IMAgINE 1 baseline, discontinuation of immunomodulators (IMMs) in patients receiving IMMs at IMAgINE 2 baseline, and linear growth improvement were reported as observed. Adverse events were assessed for patients receiving ≥1 adalimumab dose in IMAgINE 1 and 2 through January 2015.ResultsOf 100 patients enrolled in IMAgINE 2, 41% and 48% achieved remission and response (hNRI) at IMAgINE 2 week 240. Remission rates were maintained by 45% (30/67, hNRI) of patients who entered IMAgINE 2 in remission. At IMAgINE 2 week 240, 63% (12/19) of patients receiving corticosteroids at IMAgINE 1 baseline achieved corticosteroid-free remission and 30% (6/20) of patients receiving IMMs at IMAgINE 2 baseline discontinued IMMs. Adalimumab treatment led to growth velocity normalization. No new safety signals were identified.ConclusionsEfficacy and safety profiles of prolonged adalimumab treatment in children with Crohn's disease were consistent with IMAgINE 1 and adult Crohn's disease adalimumab trials.

| S-EPMC5319394 | biostudies-literature

Efficacy and safety of vedolizumab in Crohn's disease in patients from Asian countries in the GEMINI 2 study.

Project description:Background/aimsThe efficacy and safety of vedolizumab in moderate-to-severely active Crohn's disease (CD) were demonstrated in the GEMINI 2 study (NCT00783692). This post-hoc exploratory analysis aimed to assess the efficacy and safety of vedolizumab in the subgroup of patients from Asian countries.MethodsDuring the induction phase (doses at day 1, 15), clinical remission, enhanced clinical response, and change in C-reactive protein at 6 weeks; during the maintenance phase, clinical remission, enhanced clinical response, glucocorticoid-free remission and durable clinical remission at 52 weeks, were the efficacy outcomes of interest. Efficacy and safety of vedolizumab compared to placebo were assessed in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) using descriptive analyses.ResultsDuring the induction phase, in Asian countries (n = 51), 14.7% of the vedolizumab-treated patients achieved clinical remission at week 6 compared to none with placebo (difference, 14.7%; 95% confidence interval, 15.8%-43.5%). In non-Asian countries (n = 317), the remission rate at week 6 with vedolizumab was 14.5%. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks and placebo were 41.7%, 36.4%, and 0%, respectively; while enhanced clinical response rates were 41.7%, 63.6%, and 42.9%, respectively. During induction, 39.7% of patients with vedolizumab experienced an adverse event compared to 58.8% of patients with placebo, and vedolizumab was generally well-tolerated.ConclusionsThis post-hoc analysis demonstrates the treatment effect and safety of vedolizumab in moderateto-severely active CD in patients from Asian countries.

| S-EPMC7873405 | biostudies-literature

A phase 2, open label single arm study for evaluating safety & efficacy of apremilast in the treatment of cutaneous disease in patients with recalcitrant dermatomyositis.

Project description:Purpose: Studying the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis. Studying the mechanism of action of apremilast in dermatomyositis by performing RNA sequencing and immunohistochemistry on skin biopsies before and after treatment. Methods: We enrolled 8 patients with recalcitrant dermatomyositis. Apremilast 30 mg orally twice daily was added to a stable treatment regimen of steroids and/or steroids sparing agents and patients were followed for 7 months. A CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly till month 7. Skin biopsies were performed at baseline and 3-months post-apremilast to study gene expression alterations. Results: Our ORR assessed at 3 months post apremilast was 87.5%. The response was maintained at 6 months with continued decrease in CDASI and improvement in DLQI. The mean decrease in CDASI was 12.9 points (p<0.05). Apremilast was well tolerated and without any grade 3 or higher adverse events using CTCAE version 5. RNA sequencing was performed on skin biopsies from 7 patients before and 3 months after apremilast. Out of 39,076 expressed genes, there were 195 whose expression changed ≥2-fold at P<0.01 (123 down- and 72 up-regulated), several genes are known JAK-STAT targets. Using GSEA analysis, we identified 13 pathways significantly downregulated by apremilast, notably STAT1, STAT3, IL-2, IL-6, IL-12, IL-23, INFγ, and TNFα pathways. Immunohistochemical staining confirmed JAK/STAT signaling inhibition at the protein level. Conclusions: Apremilast is a safe and efficacious add-on treatment in recalcitrant dermatomyositis with an overall response rate of 87.5%, and functions through downregulation of JAK/STAT signaling in dermatomyositis.

2022-01-11 | GSE193276 | GEO

Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn's Disease Patients Stratified by Age.

Project description:IntroductionThe efficacy and safety of vedolizumab, a gut-selective α4β7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18-80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials.MethodsSafety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years.ResultsAt baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn's disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person-years) and adverse events leading to hospitalization (14.8 per 100 person-years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death.ConclusionsThe safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted.FundingMillennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).

| S-EPMC5331094 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data