Efficacy (Induction of Response/Remission) and Safety Study in Patients With Moderate to Severe Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate if Leukine can induce clinical response or remission in patients with Crohn's disease.

Detailed Description
-----------------
On 29 May 2009, Bayer began transitioning the sponsorship of this trial to Genzyme. NOTE: This study was originally posted by sponsor Berlex, Inc. Berlex, Inc. was renamed to Bayer HealthCare, Inc.

Official Title
-----------------
Randomized, Double-Blind, Placebo-Controlled, Phase 3 Induction Study to Assess the Efficacy and Safety of 6µg Sargramostim (Leukine) Administered Subcutaneously Once Daily for 8 Weeks in Patients With Active Crohn's Disease

Conditions
-----------------
Crohn Disease

Intervention / Treatment
-----------------
* Drug: Sargramostim (Leukine)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Male or female, age >/= 18 years Confirmed diagnosis of Crohn's disease (endoscopic or radiological evaluation) at least 4 months prior to receiving the first dose of study drug Moderately to severely active Crohn's disease at time of screening (i.e., CDAI greater than or equal to 220 and less than or equal to 475 points) If under treatment for Crohn's disease, medication must be stable for at least 4 weeks prior to receiving the first dose of study drug. The following therapies are allowed: Oral therapy with salicylates (mesalamine, sulfasalazine, olsalazine, or balsalazide) for Crohn's disease Antibiotics or probiotics for Crohn's disease Topical rectal therapy with mesalamine Females of child-bearing potential: Negative pregnancy test within 72 hours prior to receiving the first dose of study drug Sexually-active males and females of child-bearing potential: Agreement to use adequate method of contraception throughout the study Ability to self-inject study drug or availability of a designee who can do so Exclusion Criteria: Pregnancy or breast-feeding Colostomy or ileostomy Immediate need for gastrointestinal (GI) surgery for active GI bleeding, peritonitis, intestinal obstruction, or intra-abdominal or perianal abscess requiring surgical drainage GI surgery within 6 months prior to receiving the first dose of study drug Symptoms of bowel obstruction or confirmed evidence of a clinically-significant stricture within the last 6 months that has not been surgically corrected Positive stool test results for any of the following: Bacteria: Salmonella spec. Shigella spec. Campylobacter spec. Bacterial toxin: Clostridium difficile Ova and parasites: Amoeba spec. Giardia spec. Cryptosporidium spec. Any of the following laboratory abnormalities: Serum creatinine >/= 2.0 mg/dL Alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin >/=; 2 x the upper limit of normal Hemoglobin (Hgb) < 8.0 g/dL Absolute neutrophil count (ANC) </= 1,000 cells/µL or > cells 20,000/µL Planned in-patient hospitalization during the study Presence or history of cancer of any type (except treated basal cell carcinoma) or definite dysplasia of the colon within the last 5 years Use of any of the following medications during the specified period of time prior to receiving the first dose of study drug: At any time: Recombinant human GM CSF (sargramostim or molgramostim) Granulocyte colony-stimulating factor (G CSF; filgrastim or pegfilgrastim) Natalizumab 8 weeks: or 5 half-lives (whichever is longer) Licensed/registered and/or experimental anti-tumor necrosis factor (TNF) therapy such as infliximab or adalimumab 4 weeks: 6-mercaptopurine Azathioprine Cyclophosphamide Methotrexate Mycophenolate mofetil Tacrolimus Cyclosporine Thalidomide Glucocorticoids, including budesonide and prednisone, or local glucocorticoid therapy for Crohn's disease Any other immunosuppressive drugs Use of any investigational drug within 4 weeks or 5 half-lives (whichever is longer) prior to receiving the first dose of study drug Use of nutritional therapy (parenteral nutrition or enteral nutrition with elemental or semi-elemental diets) within 4 weeks prior to receiving the first dose of study drug. If the physician judges that nutritional supplementation is needed, enteral nutritional supplements will be allowed for patients who have been receiving a stable regimen for at least 4 weeks prior to receiving the first dose of study drug and that is intended to continue through the 8 week treatment period. History of allergy to yeast products or to sargramostim or to any other excipient of the study drug formulation Active drug or alcohol abuse Clinically important co-morbid conditions unrelated to Crohn's disease as determined by the investigator Previous randomization into this study, or into any other study of the sponsor's sargramostim development program

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Sargramostim (Leukine)<br>* Sargramostim 6 mcg/kg subcutaneously once daily<br>* Other names: BAY86-5326;|
| Placebo Comparator: Arm 2<br> | Drug: Placebo<br>* Placebo subcutaneously once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To induce clinical remission and/or clinical response following 8 weeks of treatment |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety profile of sargramostim (including development of antibodies against sargramostim) |  | During study treatment | 
| To assess quality of life (QoL) |  | During study treatment |