Comparison of 2 Immunomodulator Withdrawal Schemes for Infliximab Monotherapy in Active Pediatric Crohn's Disease After Thiopurine Failure

NCT01802593 | Terminated Phase 4 DMC

• 1 other identifier: 0169-12-WOMC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the present study is to evaluate the best regimen for infliximab monotherapy, and to evaluate if limited combination therapy with IFX and an Immunomodulator for the first 6 months of therapy, in prior Immunomodulator failures, is superior to monotherapy with Immunomodulator cessation from the second infusion, in preventing loss of remission to IFX.

Conditions

Crohn's Disease

Keywords

Pediatric; Crohn's disease; Infliximab; Thiopurine

Outcome Measures

Primary Outcomes (1)

• Complete or partial LAR (lack of remission)

  * Complete LAR- Patient failing to achieve remission after first 3 scheduled doses , or absence of remission 7 days after an infliximab infusion in a patient who had achieved remission after any previous infusion, and unresponsive to dose escalation or dose interval change, or relapse occurring less than 4 weeks after last infusion * Partial LAR- Relapse 4-8 weeks after previous infusion, with requirement for dose escalation or shortening of infliximab schedule, and remission with change in dosing or interval.

  76 weeks

Secondary Outcomes (6)

• Mean trough level

  14 and 52 weeks

• Sustained steroid free remission

  52 and 76 weeks

• Presence of ATI

  52 weeks

• Corticosteroid free remission

  14 weeks

• Hospitalizations for LOR (loss of response) or failure to obtain remission

  Up to 76 weeks

Study Arms (2)

Immunomodulator therapy 26 weeks

EXPERIMENTAL

IFX 5mg/kg for 76 weeks, continuing immunomodulator for 6 months from first infusion

Drug: AZATHIOPRINE or METHOTREXATE

Immunomodulator therapy 2 weeks

EXPERIMENTAL

IFX 5mg/kg induction for 76 weeks, discontinuing immunomodulator on day of second infusion( after 14 days).

Drug: AZATHIOPRINE or METHOTREXATE

Interventions

AZATHIOPRINE or METHOTREXATE DRUG

Patients should continue azathioprine or 6 MP or methotrexate at their previous doses for 6 months IMM therapy 26 weeks

Also known as: 6 MERCAPTOPURINE

Immunomodulator therapy 26 weeks

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Crohns disease
• Age: 6 - 18 years ( inclusive)
• Active disease PCDAI \>10, or any steroid dependence despite thiopurine use for \>10 weeks.
• Naïve to biologics
• Informed consent
• CRP ≥0.6 mg/dl
• Neg. TB-Test, negative HBV- S Ag
• Use of IMM at present or in past for at least 10 weeks ( for Withdraw only).
• Negative stool culture, parasites and clostridium toxin current flare
• Patients receiving corticosteroids may be included if the disease is active and CRP elevated.
• All other treatments such as 5ASA , , must be discontinued immediately after the first IFX infusion.
• Patients may receive an antihistamine prior to any infusion.Use of corticosteroid pretreatment is allowed only during the first two infusions (single infusion on day of infliximab), or if an infusion reaction has occurred.
• Partial enteral nutrition, accounting for less than 50% of daily required calories, may be supplied as needed.
• Patients receiving antibiotics must cease use of antibiotics within the 14 days of receiving the first infusion.
• ESR \>20 can be alternative if the CRP \<0.6.

You may not qualify if:

• Intolerance to thiopurines/methotrexate
• Pregnancy
• Contraindication for any of the drugs.
• Leukopenia \<4000 or absolute neutrophil count below 1200 on two consecutive tests during screening.
• Hepatocellular Liver disease ( ALT \> 60 ) or cirrhosis.
• Renal Failure
• Prior idiosyncratic side effects with thiopurines ( pancreatitis etc).
• Current abscess ( \< 14 days of antibiotics) or perforation of the bowel( \<14 days antibiotics).
• Small bowel obstruction within the last 3 months
• Fixed non inflammatory stricture with predilatation with symptoms related to stricture
• Prior treatment with infliximab
• Previous malignancy
• Toxic Megacolon
• Sepsis
• Surgery related to Crohn's disease in previous 8 weeks.

Sponsors & Collaborators

• Prof. Arie Levine: lead

Study Sites (1)

The E. Wolfson.Medical Center

Holon, 58100, Israel

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Azathioprine; Methotrexate; Mercaptopurine

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Sulfhydryl Compounds

Study Officials

• Arie Levine, MD

  Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson MC, Tel-Aviv University, Holon, Israel

  STUDY CHAIR

• Dan Turner, MD, PhD

  Pediatric Gastroenterology and Nutrition Unit, The Hebrew University of Jerusalem, Shaare Zedek MC, Jerusalem, Israel

  STUDY DIRECTOR

• Raanan Shamir, MD

  Schneider Childrens Hospital

  PRINCIPAL INVESTIGATOR

• Michal Kori, MD

  Kaplan Medical Center

  PRINCIPAL INVESTIGATOR

• Michael Wilshanski, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

• Ron Shaoul, MD

  Meyer Childrens Hospital Rambam, Haifa, Israel

  PRINCIPAL INVESTIGATOR

• Shlomi Cohen, MD

  Tel Aviv Medical Center

  PRINCIPAL INVESTIGATOR

• Batia Weiss, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

• Sarit Peleg, MD

  Afula Hospital

  PRINCIPAL INVESTIGATOR

• Baruch Yerushalmi, MD

  Soroka University Medical Center

  PRINCIPAL INVESTIGATOR

• Efrat Broide, MD

  Asaf Harofe Medical Center

  PRINCIPAL INVESTIGATOR

• Avi On, MD

  Poriah Hospital

  PRINCIPAL INVESTIGATOR

• Hussein Chemali, MD

  Nazheret Hospital

  PRINCIPAL INVESTIGATOR

• Aharon Lerner, MD

  Carmel Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Pediatric Gastroenterology and Nutrition unit.

Study Record Dates

• First Submitted: December 24, 2012
• First Posted: March 1, 2013
• Study Start: February 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 22, 2015

Record last verified: 2015-12

Locations

IL (1)