Clinical trial NCT01674413: Calprotectin-Directed Humira® Maintenance Therapy (CADHUM)
Official title: Calprotectin-Directed Humira® Maintenance Therapy, a Double-blind, Double-dummy, Randomized Controlled Trial in Crohn's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Crohn's
Crohns
Inflammatory Bowel Disease
IBD
Humira
Adalimumab
Adalimumab injection
Higgins
Calprotectin
biomarkers
Gastroenterology
University of Michigan
U of M
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2012-08-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study that invites adults with Crohn's disease and have been responding well to Adalimumab (Humira ®) for at least 6 months. Patients frequently discontinue maintenance medications in Crohn's disease, particularly when in remission. Patients want to know that they truly need to take a medication, yet they don't want to have flares. The purpose of this study is to see that if we monitor the patient, along with looking at changes in their stool samples, we can safely stop the maintenance medication Adalimumab for up to 48 weeks, or add as-needed dosing only, and keep them in remission.

Detailed description: Patients frequently discontinue maintenance medications in Crohn's disease, particularly when in remission. Patients want to know that they truly need to take a medication, yet they don't want to have flares. As a biomarker, fecal calprotectin \< 167 has a 100% negative predictive value for flare within the next 12 weeks (Gisbert, 2009). Adalimumab has low antigenicity, and can be safely stopped and restarted later with good clinical effect (Colombel, 2007). Patients want intermittent therapy, if it can be delivered in a timely fashion when pre-clinical inflammation starts, in order to avoid clinically-significant flares. This study will combine monitoring for pre-clinical inflammation with fecal calprotectin and as-needed dosing with Adalimumab to maintain remission in patients who have obtained remission with Adalimumab. This will be compared to two comparator arms: standard maintenance therapy and complete cessation of therapy (Step-Down approach).

Eligibility criteria: Inclusion Criteria:

1. Men or women 18 years of age or older at the time of informed consent.
2. Crohn's disease confirmed by endoscopy with biopsies.
3. On maintenance Adalimumab at a dose of 40 mg SC q 2 weeks without concomitant immunosuppressive therapy.
4. Must be in clinical remission (CDAI \<150) at the baseline/randomization (Week 0) visit and biologic remission (both CRP \<0.8 and FCP \<167)at Week 0.
5. Prior medication for Crohn's disease may include one of the following and must have been stopped with wash out periods: Methotrexate, Azathioprine, 6-Mercaptopurine, Tacrolimus, Steroids.
6. Negative for TB, Hepatitis B-negative, and negative stool for Clostridium difficile.

Exclusion Criteria

1. Unable to consent for themselves.
2. Are prisoners, students or employees of the investigators, or mentally incapacitated.
3. Are unwilling to complete this 48 week study, provide stool samples throughout, or unwilling to undergo multiple venipunctures.
4. Have a current infection with Clostridium difficile, clinically-significant intestinal stricture, history of allergy, or adverse reaction, to Adalimumab, history of sensitivity to latex.
5. Are currently using steroids or systemic immunomodulators (MTX, AZA, 6-MP, or Tacrolimus), or have used another biologic medication in the past 12 weeks other than Adalimumab, or have current or past use of Kineret® (Anakinra) or Tysabri® (natalizumab).
6. Have received any live bacterial or viral vaccinations ≤ 12 weeks prior to Week 0 and must not receive 12 months after study as well as BCG vaccination
7. Are known to have congestive heart failure.
8. Have a history of, or ongoing chronic or recurrent infectious disease, including but not limited to chronic renal, chest infection (i.e. bronchiectasis) or urinary tract infection (i.e. recurrent pyelonephritis) or open, draining, or infected skin wounds or ulcers.
9. Have evidence of current clinically active and important infection.
10. Have or ever had a non-tuberculous mycobacterium infection or serious opportunistic infection (i.e. cytomegalovirus, Pneumocystis carinii, aspergillosis).
11. Are known to be infected with HIV, Hepatitis B, or Hepatitis C.
12. Have severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof.
13. Have a known history of lymphoproliferative disease including lymphoma. Have a history of certain malignancies within five years of screening.

Primary outcomes:
measure: Percent Time in Remission (PTIR) in PRNLOAD vs. Placebo arms
timeFrame: 48 weeks
Secondary outcomes:
measure: Percent Time in Remission MAINT vs. PRNLOAD
timeFrame: 48 weeks
measure: Percent Time in Remission MAINT vs. PBO
timeFrame: 48 weeks.
measure: Strict Biologic Remission Rates
timeFrame: 48 weeks
measure: Subject acceptability
timeFrame: 48 weeks
measure: Subject preference
timeFrame: 48 weeks
measure: Equivalence of Percent Time in Remission
timeFrame: 48 weeks
measure: Comparison of Average CDAI
timeFrame: 48 weeks
measure: Comparison of average IBDQ
timeFrame: 48 weeks
measure: Comparison of average FCP
timeFrame: 48 weeks
measure: Comparison of average CRP
timeFrame: 48 weeks
measure: Comparison of Rates of Hospitalization
timeFrame: 48 Weeks
measure: Comparison of Rates of Emergency Department visits
timeFrame: 48 Weeks
measure: Comparison of Rates of Physician visits
timeFrame: 48 Weeks
measure: Comparison of mg prednisone prescribed
timeFrame: 48 Weeks
Other outcomes:
measure: Anti-Adalimumab antibodies
timeFrame: 0, 48 weeks
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
Study officials:
affiliation: University of Michigan
name: Peter D Higgins, MD, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
References: