Calprotectin-Directed Humira® Maintenance Therapy (CADHUM)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2013 by University of Michigan
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Peter Higgins, University of Michigan
ClinicalTrials.gov Identifier:
NCT01674413
First received: August 16, 2012
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Crohn's Disease
Drug: Adalimumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Calprotectin-Directed Humira® Maintenance Therapy, a Double-blind, Double-dummy, Randomized Controlled Trial in Crohn's Disease

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Percent Time in Remission (PTIR) in PRNLOAD vs. Placebo arms [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Determine whether adding as-needed q 12 weeks Adalimumab re-loading (160 mg/80 mg) when FCP ≥167 mcg/gram of stool can improve the maintenance of remission in Crohn's disease patients who stop Adalimumab therapy (PRNLOAD Arm) compared to the placebo arm. Endpoint: Percent time in remission (q 4 week evaluation for 48 weeks).


Secondary Outcome Measures:
  • Percent Time in Remission MAINT vs. PRNLOAD [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Compare the percent of monitoring visits in which the subject is in remission in each arm between the MAINT and PRNLOAD arms.

  • Percent Time in Remission MAINT vs. PBO [ Time Frame: 48 weeks. ] [ Designated as safety issue: No ]
    Compare the percent of monitoring visits in which the subject is in remission in each arm between the MAINT and PBO arms.

  • Strict Biologic Remission Rates [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Percent of visits with strict biologic remission (FCP <50 and CRP <0.5) with 3 comparisons: PRNLOAD vs. PBO, MAINT vs. PRNLOAD, MAINT vs. PBO

  • Subject acceptability [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measure subject acceptability of repeated stool sampling.

  • Subject preference [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Measure subject preference for the MAINT versus PRNLOAD regimen.

  • Equivalence of Percent Time in Remission [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Compare percent time in remission (CDAI <150) over 48 weeks, evaluation every 4 weeks across 3 arms (chi square test).

  • Comparison of Average CDAI [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Compare average CDAI over 48 weeks, evaluation every 4 weeks across 3 arms (ANOVA).

  • Comparison of average IBDQ [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Compare average IBDQ over 48 weeks, evaluation every 4 weeks across 3 arms (ANOVA).

  • Comparison of average FCP [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Compare average FCP over 48 weeks, evaluation every 12 weeks across 3 arms (ANOVA).

  • Comparison of average CRP [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Compare average CRP over 48 weeks, evaluation every 12 weeks across 3 arms (ANOVA).

  • Comparison of Rates of Hospitalization [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Comparison of Rates of Hospitalization across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).

  • Comparison of Rates of Emergency Department visits [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Comparison of Rates of Emergency Department visits across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).

  • Comparison of Rates of Physician visits [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Comparison of Rates of Physician visits across all 3 arms - hospital admissions per patient over 48 weeks (ANOVA).

  • Comparison of mg prednisone prescribed [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Comparison of average milligrams of prednisone prescribed across all 3 arms - over 48 weeks (ANOVA).


Other Outcome Measures:
  • Anti-Adalimumab antibodies [ Time Frame: 0, 48 weeks ] [ Designated as safety issue: Yes ]
    Measure anti-Adalimumab antibody titers in patients at week 0 and 48 weeks (or exit visit). Compare average titers across 3 arms (ANOVA)


Estimated Enrollment: 54
Study Start Date: October 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo/Step-Down
1 syringe of placebo SC q 2 weeks.
Drug: Placebo
1 syringe of placebo SC q 2 weeks, with additional placebo loading of 3 syringes/1 syringe at Weeks 0/2, 12/14, 24/26, and 36/38 Weeks.
Other Name: Placebo
Active Comparator: PRNLOAD Arm
160 mg/80 mg Adalimumab at Weeks 0 and 2, followed by 1 syringe SC placebo q 2 weeks (except at Weeks 12/14, 24/26, and 36/38)
Drug: Adalimumab

160 mg/80 mg Adalimumab at Weeks 0 and 2, followed by 1 syringe SC placebo q 2 weeks (except at Weeks 12/14, 24/26, and 36/38), with

  • PRNLOADing of 160 mg/80 mg Adalimumab at Weeks 12/14, 24/26, or 36/38 if most recent FCP is ≥167 mcg/gram of stool,
  • Or, placebo loading of 4 syringes/2 syringes at Weeks 12/14, 24/26, and 36/38 if most recent FCP is < 167 mcg/gram of stool.
Other Name: Humira
Active Comparator: Maintenance Arm
Adalimumab 40 mg q 2 weeks.
Drug: Adalimumab
Adalimumab 40 mg q 2 weeks, with placebo loading of 3 syringes/1 syringe at Weeks 0/2, 12/14, 24/26, and 36/38
Other Name: Humira

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01674413

Contacts
Contact: Katy Patten, B.Sc. 734-615-4843 pattenk@med.umich.edu
Contact: Kay Sauder, B.Sc. 734-647-2564 ksauder@umich.edu

Locations
United States, Michigan
University of Michigan Health System Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Katy Patten, BSc    734-615-4843    pattenk@med.umich.edu   
Contact: Kay Sauder, BSc    734-647-2564    ksauder@umich.edu   
Sponsors and Collaborators
Peter Higgins
AbbVie
Investigators
Principal Investigator: Peter D Higgins, MD, PhD, MSc University of Michigan
  More Information

No publications provided

Responsible Party: Peter Higgins, M.D., Ph.D., MSc. Assistant Professor of Medicine, University of Michigan
ClinicalTrials.gov Identifier: NCT01674413     History of Changes
Other Study ID Numbers: Abbott IMM 10-0105, Abbott IMM 10-0105
Study First Received: August 16, 2012
Last Updated: June 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
Crohn's Disease
Crohn's
Crohns
Inflammatory Bowel Disease
IBD
Humira
Adalimumab
Adalimumab injection
Higgins
Calprotectin
biomarkers
Gastroenterology
University of Michigan
U of M

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Adalimumab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 20, 2014