Crohn's Disease Treatment Studies


AMG 181

A randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of AMG 181 in subjects with moderate to severe Crohn’s disease

Enrollment status: UPCOMING

Study Coordinator: Katy Patten, (734) 615-4843, higginsSCteam@umich.edu

Drug: AMG 181 protein – subcutaneous injection (under the skin)

This is a phase 2 placebo-controlled, multiple dose study to evaluate the efficacy of AMG 181 compared with placebo as measured by the proportion of subjects in remission (CDAI score < 150) at week 8. AMG 181 is a fully human monoclonal immunoglobulin IgG2 antibody that specifically recognizes the human α4β7 integrin heterodimer. AMG 181 binds α4β7 with high affinity and blocks its interaction with MAdCAM-1. This mechanism of action of AMG 181 reduces pathological bowel inflammation. Subjects will be randomized in a 2:1:2:1 ratio to receive placebo or AMG 181 21 mg, 70 mg, or 210 mg. At the end of the double-blind period (week 24), subjects will enter a 108-week open-label period during which all subjects will receive open-label 210 mg AMG 181 every 3 months.


Tofacitinib for Crohn’s disease

A randomized, double-blind, placebo-controlled, parallel group, multi-centre study to investigate the safety and efficacy of CP-690,550 for induction therapy in subjects with moderate to severe Crohn’s disease

Enrollment status: UPCOMING

Study Coordinator: Kay Sauder, (734) 647-2564, higginsSCteam@umich.edu

Drug: Tofacitinib (CP-690,550) – oral medication

This is a phase 2b study of subjects with moderately to severely active Crohn’s disease. The medicine is a JAK inhibitor made by Pfizer. JAK inhibition is a novel approach for treating a variety of autoimmune and inflammatory diseases. JAK inhibitors interrupt signaling downstream of a multiplicity of cytokines, rather than blocking one cytokine at a time, as in case of anti-TNF or interleukin-6 blockers. It is taken in pill form.

The study lasts 8 weeks and involves a screening visit, a week 0/baseline appointment, follow-up visits at week 2, week 4, and week 7 to assess response to the medicine. Finally, at week 8 we will assess the subject’s eligibility to continue in the program. Those who complete the treatment period and meet the definition of clinical response or clinical remission will be eligible to enter a placebo-controlled maintenance study of 26 weeks and then the open-label extension study, meaning there is no placebo and you are guaranteed active drug.


PEBBLE

A phase 2a study to evaluate the efficacy and safety of MEDI2070 in subjects with moderate to severe Crohn’s disease who have failed or are intolerant to anti-tumor necrosis factor–alpha therapy. Protocol D5170C00001

Enrollment Status: OPEN

Study Coordinator: Katy Patten, (734) 615-4843, higginsSCteam@umich.edu

Drug: MEDI2070 – subcutaneous injection (under the skin) and intravenous (IV) infusion

This is phase 2 study of a new anti-IL 23 biologic randomizes patients 1:1 to biologic or placebo. The IL-23 blockade is expected to work like ustekinumab (Stelara®), but may have a more direct benefit. After 12 weeks, all patients can roll over to open-label maintenance therapy with active drug. This open-label extension can provide free drug for patients for up to 2 years.


UNITI 1, UNITI 2, IMUNITI

A phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety and efficacy of ustekinumab induction therapy in subjects with moderately to severely active Crohn's disease

Enrollment Status: OPEN for UNITI 2

Study Coordinator: Siera Goodnight, (734) 647-1092, higginsSCteam@umich.edu

Drug: Ustekinumab (Stelara®) – intravenous (IV) infusion and subcutaneous injection (under the skin)

Ustekinumab is a fully humanized monoclonal antibody that blocks activity of interleukin 12/23. It is approved in psoriasis and psoriatic arthritis (brand name Stelara). Ustekinumab showed promising efficacy in Centocor’s phase 2a study (C0379T07) in patients who had failed conventional Crohn's disease therapy (Sandborn et al, 2008) and in Centocor’s Phase 2b study (C0743T26) of ustekinumab in Crohn's disease patients who had failed or were intolerant to TNF antagonist therapy. This is the next study of this series, which will evaluate the efficacy of IV induction regimens of ustekinumab in inducing clinical response in subjects with moderately to severely active Crohn's disease who have failed or are intolerant to one or more TNF antagonist therapies. Subjects in UNITI 2 are TNF naïve.

Appointments are at screening, week 0 (drug administration via IV infusion over 1 hour), week 3, week 6, and week 8. At the week 8 appointment, subjects have the option to enter the maintenance study (IMUNITI) in which they will be re-randomized and given the study drug every 4 weeks, for up to 4 years.