Tu2019 - Engraftment of Ser-287, an Investigational Microbiome Therapeutic, is Related to Clinical Remission in a Placebo-Controlled, Double-Blind Randomized Trial (Seres-101) in Patients with Active Mild to Moderate Ulcerative Colitis (UC)

2018 ◽  
Vol 154 (6) ◽  
pp. S-1371-S-1372 ◽  
Author(s):  
Sheri Simmons ◽  
Liyang Diao ◽  
Edward O'Brien ◽  
Meghan Chafee ◽  
Jeff Zhao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Randomized Trial ◽  
Clinical Remission ◽  
Double Blind

Improved Insulin Sensitivity in 80 Nondiabetic Patients With MDD After Clinical Remission in a Double-Blind, Randomized Trial of Amitriptyline and Paroxetine

2006 ◽  
Vol 67 (12) ◽  
pp. 1856-1861 ◽  
Author(s):  
Bettina Weber-Hamann ◽  
Maria Gilles ◽  
Florian Lederbogen ◽  
Isabella Heuser ◽  
Michael Deuschle
Keyword(s):  
Insulin Sensitivity ◽  
Randomized Trial ◽  
Clinical Remission ◽  
Double Blind

scholarly journals A Multicentre, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of the S1P Receptor Agonist KRP203 in Patients with Moderately Active Refractory Ulcerative Colitis

2020 ◽  
Vol 5 (4) ◽  
pp. 180-190
Author(s):  
Heinfried H. Radeke ◽  
Jürgen Stein ◽  
Gert Van Assche ◽  
Gerhard Rogler ◽  
Peter L. Lakatos ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Receptor Subtype ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Peripheral Lymphocytes ◽  
Mayo Score ◽  
Parallel Group ◽  
The Difference ◽  
Improved Design

<b><i>Background and Aims:</i></b> KRP203 is a potent oral agonist of the sphingosine-1-phosphate receptor subtype 1 that induces the sequestration of peripheral lymphocytes, thereby potentially reducing the number of activated lymphocytes circulating to the gastrointestinal tract. <b><i>Methods:</i></b> We conducted a multicentre, double-blind, placebo-controlled, parallel-group, proof-of-concept study to evaluate the efficacy, safety, and tolerability of KRP203 in patients with moderately active 5-aminosalicylate-refractory ulcerative colitis (UC). Patients were randomly assigned to receive 1.2 mg KRP203 or placebo daily for 8 weeks. Primary efficacy variable was clinical remission, defined as partial Mayo Score 0–1 and modified Baron Score 0–1 with rectal bleeding subscore 0. <b><i>Results:</i></b> KRP203 was safe and well tolerated overall. The most common adverse events (AEs) were gastrointestinal disorders and headache. Importantly, no KRP203-related cardiac AEs were reported. Total peripheral lymphocytes and selectively affected lymphocyte subtypes decreased, causing marked decreases in naive and central memory CD4+ and CD8+ T cells, and also in B cells. Clinical remission occurred in 2/14 (14%) patients under KRP203, compared with 0/8 (0%) under placebo. <b><i>Conclusions:</i></b> Overall, KRP203 was safe and well tolerated by patients with UC. Importantly, no cardiac AEs were reported. Although KRP203 did not meet the minimum clinically relevant threshold for efficacy, the results may suggest that KRP203 treatment is superior to placebo. However, in this small study population, the difference was insignificant. Based on these data, studies with an improved design and a larger population should be considered.

scholarly journals OP25 Efficacy of filgotinib in patients with Ulcerative Colitis by line of therapy in the phase 2b/3 SELECTION trial

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S024-S026
Author(s):  
L Peyrin-Biroulet ◽  
I Dotan ◽  
T Hibi ◽  
V Taliadouros ◽  
A Oortwijn ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Controlled Trial ◽  
Janus Kinase ◽  
Double Blind ◽  
Once Daily ◽  
Janus Kinase 1 ◽  
Induction Study ◽  
Line Of Therapy ◽  
Maintenance Study

Abstract Background Patients with ulcerative colitis (UC) often do not respond to treatment or lose response over time, and thus switch between therapies with various mechanisms of action (MoAs).1 Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor in development as a UC treatment. We assessed the efficacy of FIL in biologic (bio)-naïve and bio-experienced patients with UC, and in bio-experienced patients with failure of 1 or ≥2 biologics or 1 or 2 MoAs. Methods SELECTION (NCT02914522) was a phase 2b/3 double-blind, randomised, placebo-controlled trial comprising two induction studies and a maintenance study. Adults (18–75 years) with moderately to severely active UC were randomised 2:2:1 to FIL 200 mg, FIL 100 mg or placebo (PBO) once daily for 11 weeks in Induction Study A (bio-naïve) and B (bio-experienced). Patients in either clinical remission or Mayo Clinic Score (MCS) response at week 10 (responders) could enter the Maintenance Study. Responders who received induction FIL were re-randomised 2:1 to continue their induction regimen or PBO through week 58. Responders who received induction PBO continued PBO. We assessed clinical remission and MCS response at weeks 10 and 58 in bio-naïve patients and bio-experienced patients with failure of 1 or ≥2 biologics and 1 or 2 MoAs (TNF antagonists and vedolizumab). All p values for subgroup analyses are nominal. Results At week 10, clinical remission was achieved by a significantly higher proportion of bio-naïve and -experienced patients treated with FIL 200 mg than PBO (Figure 1a). A higher proportion of bio-experienced patients with 1 biologic or MoA failure treated with FIL 200 mg than PBO achieved clinical remission at week 10 (p&lt;0.05); a smaller treatment effect was seen in patients with ≥2 biologic or 2 MoA failures (Figure 1b). None of these comparisons reached p&lt;0.05 for FIL 100 mg. Higher proportions of patients treated with either dose of FIL than PBO achieved MCS response at week 10 in all (sub)groups (Figure 2). At week 58, higher proportions of bio-naïve and -experienced responders, and bio-experienced responders with ≥2 biologic or 2 MoA failures treated with maintenance FIL 200 mg than PBO achieved clinical remission (p&lt;0.05) (Table 1). Higher proportions of responders treated with maintenance FIL 200 mg than PBO achieved MCS response at week 58 in all (sub)groups. Conclusion FIL 200 mg was effective in inducing and maintaining clinical remission in bio-naïve and -experienced patients. Induction results suggest FIL 200 mg is most effective in bio-naïve patients, and those who switch after failure of 1 biologic or MoA. Interpretation of week 58 data is limited by low patient numbers. Reference

scholarly journals Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial

2020 ◽  
Author(s):  
Toshihiro Kita ◽  
Sinya Ashizuka ◽  
Naoki Ohmiya ◽  
Takayuki Yamamoto ◽  
Takanori Kanai ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trial ◽  
Clinical Remission ◽  
High Dose ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Steroid Resistant ◽  
Double Blind Placebo ◽  
Mayo Score ◽  
Secondary Endpoints

Abstract Background Adrenomedullin (AM) is a bioactive peptide having many pleiotropic effects, including mucosal healing and immunomodulation. AM has shown beneficial effects in rodent models and in preliminary study for patients with ulcerative colitis (UC). We performed a clinical trial to investigate the efficacy and safety of AM in patients with UC. Methods This was a multi-center, double-blind, placebo-controlled phase-2a trial evaluating 28 patients in Japan with steroid-resistant UC. Patients were randomly assigned to four groups and given an infusion of 5, 10, 15 ng/kg/min of AM or placebo for 8 h per day for 14 days. The primary endpoint was the change in Mayo scores at 2 weeks. Main secondary endpoints included the change in Mayo scores and the rate of clinical remission at 8 weeks, defined as a Mayo score 0. Results No differences in the primary or secondary endpoints were observed among the four groups at 2 weeks. Despite the insufficient tracking rate, the Mayo score at 8 weeks was only significantly decreased in the high-dose AM group (15 ng/kg/min) compared with the placebo group (− 9.3 ± 1.2 vs. − 3.0 ± 2.8, P = 0.035), with its rate of clinical remission at 8 weeks being significantly higher (3/3, 100% vs. 0/2, 0%, P = 0.025). We noted mild but no serious adverse events caused by the vasodilatory effect of AM. Conclusions In this double-blind randomized trial, we observed the complete remission at 8 weeks in patients with steroid-resistant UC receiving a high dose of AM. Clinical trial registry JAPIC clinical trials information; Japic CTI-205255 (200410115290). https://www.clinicaltrials.jp/cti-user/trial/Search.jsp.

scholarly journals OP30 Lyophilised orally administered faecal microbiota transplantation for Active Ulcerative Colitis (LOTUS study)

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S029-S029
Author(s):  
C Haifer ◽  
A Saikal ◽  
S Paramsothy ◽  
T J Borody ◽  
S Ghaly ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Remission ◽  
Controlled Trial ◽  
Active Ulcerative Colitis ◽  
Faecal Microbiota ◽  
Double Blind ◽  
Faecal Microbiota Transplantation ◽  
Endoscopic Remission ◽  
Remission Rates ◽  
Pre Treatment

Abstract Background Faecal microbiota transplantation (FMT) administered via the lower GI tract effectively induces remission in ulcerative colitis (UC). Orally administered FMT capsules may improve patient tolerability and facilitate maintenance therapy while it is unclear if pre-FMT antibiotics enhance therapeutic efficacy. Methods We performed a dual-centre randomised, double blind, placebo-controlled trial of oral lyophilised FMT in adults with mild-moderately active UC (total Mayo 4–10). All subjects received 2-weeks of pre-FMT antibiotics (amoxycillin, metronidazole and doxycycline) before 1:1 randomisation to either oral FMT (0.35g stool content per capsule from 1 of 2 healthy donors) or identical placebo for 8 weeks. Enforced tapering and cessation of corticosteroids was mandated. The primary endpoint was week 8 steroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2 with subscores ≤ 1 for rectal bleeding, stool frequency and endoscopic appearance, and ≥1-point reduction from baseline in endoscopy subscore). Responders to FMT induction were re-randomised to either continue maintenance FMT or withdrawal of FMT with final outcomes assessed at week 56. Results Recruitment was paused due to the COVID-19 pandemic. 37 patients were randomised. Baseline patient and disease characteristics were balanced between the randomised groups. The primary outcome was achieved in 8/16 (50%) receiving FMT versus 3/19 (16%) receiving placebo (OR: 4.63; 95%CI: 1.74–12.30; P=0.002). Steroid-free clinical remission rates and endoscopic remission rates were 69% vs 26% (P=0.012) and 44% vs 16% (P=0.074) in the FMT and placebo arms, respectively. Reported SAE were worsening colitis (2 FMT, 1 placebo) and PR bleeding relating to previous anal surgery (placebo). Ten patients entered the maintenance withdrawal study. Steroid-free clinical, endoscopic and histologic remission was achieved in 4/4 patients who continued daily oral FMT, with all 6 patients randomised to FMT withdrawal having a flare of disease with a median time to relapse of 6 months. Conclusion Oral lyophilised FMT following antibiotic pre-treatment for mild-moderately active ulcerative colitis was associated with a significant increased rate of clinical remission with endoscopic remission or response versus antibiotic treatment alone at week 8. Pre-treatment antibiotics had an additive impact upon treatment efficacy compared with previous studies utilising FMT. Maintenance FMT therapy was associated with sustained clinical, endoscopic and histologic remission at week 56. Treatment was well tolerated and there were no new safety signals related to FMT therapy.

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