5-aminosalicylic acid (5-ASA) medications are first line treatment for mild to moderate Ulcerative Colitis (UC), comprise 81% of all UC prescriptions, and have a market share of 1.5 billion. However, despite 5-ASA frequency and optimization, 35% of patients fail induction therapy and 52% of patients fail to maintain remission at 12 months, requiring step up therapy to immunomodulators or biologics which have increased side effects and cost. This highlights a key challenge in UC which is to address the large inter- and intrapatient variabilities in both disease progression and variability in response to treatment. Chronotherapy is the timing of medical interventions according to the host circadian rhythms in order to optimize drug response and minimize toxicity, and is one explanation for the large variability in response to medications. The long-term objective of our research is to establish the hypothesis that is that appropriate time of day of administration of oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels. To test this hypothesis, In
response to the small R01 for pilot and feasibility clinical trials (PAS-20-160) and to test our hypothesis, we propose to conduct a six month, single center, randomized crossover pilot trial involving 60 subjects with inactive UC [Mayo score ≤2, endoscopic score 0-1] but subclinical inflammation [stool calprotectin > 50 mcg/g] on a stable dose of once daily 5-ASA medication. All subjects will be randomized to once daily 5-ASA medications two different times of the day: either between 06:00 – 10:00 h or 18:00 – 22:00 h. Three disease assessments will performed at: 1) enrollment just before randomization; 2) month 3, at the completion of first arm (condition 1), and 3) month 6, after completion of the second arm (condition 2). We will assess time impact of our chronotherapy protocol on: 1) subclinical inflammation (Aim 1): a) stool calprotectin; b) intestinal barrier integrity; and c) endoscopic/histology scores; 2) Microbiota: mucosal and stool microbiota structure and function (Aim 2); and 3) 5-ASA metabolism: a) increase mucosal levels of 5-ASA and b) mucosal NAT activity (Aim 3). In addition, optimal 5-ASA treatment (i.e., Aims 1-3) will depend upon host chronotype which will be monitored by validated questionnaires, rest-wake actigraphy, and urinary melatonin. The results of this innovative proposal will establish a key role for chronotherapy in the treatment of UC and provide pilot data for the future larger multicenter clinical trials. Chronotherapy will allow for a personalized medicine approach that incorporates circadian biology to improve efficacy and minimize intolerance in treatment of UC.
This is a randomized, double-blind, active- and placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of induction and maintenance JNJ-78934804 therapy in participants with moderately to severely active CD who have had an inadequate initial response, loss of response, or intolerance to ≥1 approved ADT (advanced therapy inadequate responder [ADT-IR]). This
dose-ranging study includes participants 18 to 65 years of age (inclusive, at the time of consent) with moderately or severely active CD (defined by a CDAI score ≥220 and ≤450) and either a mean daily abdominal pain (AP) score ≥2 (based on the unweighted CDAI component of AP) or a mean daily stool frequency (SF) count ≥4 (based on the unweighted CDAI component of the number of liquid or very soft stools), of at least 3 months duration, with colitis, ileitis, or ileocolitis previously confirmed in the past by radiology, histology and/or endoscopy. Participants must also have endoscopic evidence of active ileal
and/or colonic CD on the screening video ileocolonoscopy. Overall, the study will evaluate 48 weeks of therapy with JNJ-78934804
This is a randomized, double-blind, active- and placebo-controlled, parallel group, multicenter study to evaluate the efficacy and safety of induction and maintenance JNJ-78934804 therapy in participants 18 to 65 years of age (inclusive, at the time of consent), with moderately to severely active UC as determined by a modified Mayo score ≥5 and a final reported endoscopy subscore ≥2 obtained during the central review of the screening video endoscopy. Participants must also have demonstrated an inadequate initial response, loss of response, or intolerance to ≥1 approved ADT (advanced therapy inadequate responder [ADT-IR]). Overall, the study will evaluate 48 weeks of therapy with JNJ-7893480. The primary objective of the study is to evaluate the efficacy of JNJ-78934804 at Week 48
compared with each monotherapy (guselkumab alone and golimumab alone).
This study is being done to learn more about a study drug called efavaleukin alfa in people with moderately to severely active ulcerative colitis. The purpose of the study is to evaluate if efavaleukin alfa is effective and safe in improving this condition. The study drug, efavaleukin alfa, will be compared to placebo. Efavaleukin alfa is being developed by Amgen Inc., a for-profit biopharmaceutical company. Efavaleukin alfa is still experimental and is not approved by any regulatory health agency (like the Food and Drug Administration [FDA] or European Medicines Agency [EMA]).
This is an open label, multi-center study to evaluate the long-term safety and tolerability of BMS-986165 in participants with moderate to severe CD or moderate to severe UC who have completed one of the applicable parent studies (IM011023, IM011024, and IM011127), are likely to safely derive a clinical benefit from ongoing treatment with BMS-986165, and are willing and able to participate. Participants will receive BMS-986165 6 mg BID by mouth (PO) in a tablet formulation. Approximately 300 participants are expected to rollover from the parent studies into Study IM011077. All participants must have completed 1 of the parent studies (Studies IM011023, IM011024, or Study IM011127) and must meet all eligibility criteria. The duration of the study is approximately 296 weeks (2,072 days). There will be a Qualification and enrollment period (up to 28 days), Open label study period (288 weeks), and a Post-treatment follow-up period (4 weeks).