Calprotectin-Directed Humira® Maintenance Therapy (CADHUM)

NCT ID: NCT01674413

Last Updated: 2017-05-24

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2016-03-31

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).

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo/Step-Down

1 syringe of placebo SC q 2 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

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)

Group Type: ACTIVE_COMPARATOR

Adalimumab PRN

Intervention Type: DRUG

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.

Maintenance Arm

Adalimumab 40 mg q 2 weeks.

Group Type: ACTIVE_COMPARATOR

Adalimumab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Adalimumab PRN

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Humira; Humira

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Peter Higgins

OTHER

Sponsor Role: lead

Responsible Party

Peter Higgins

M.D., Ph.D., MSc. Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Peter D Higgins, MD, PhD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Health System

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

Abbott IMM 10-0105

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Abbott IMM 10-0105

Identifier Type: -

Identifier Source: org_study_id