Safety and Efficacy of ALX-0600 in Subjects With Active Crohn's Disease

Study Overview
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Brief Summary
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The purpose of the study is to determine whether an investigational compound, ALX-0600, is safe and effective in treating Crohn's Disease.

Detailed Description
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The study is twelve weeks in duration and there are eight weeks of once-daily injections into your abdomen or thigh. There are a total of six visits.

Official Title
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A Pilot Study of the Safety and Efficacy of ALX-0600 in Subjects With Moderately Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: ALX-0600
* Drug: placebo
* Drug: teduglutide 0.05
* Drug: teduglutide 0.2 mg
* Drug: Teduglutide 0.05 dose
* Drug: teduglutide 0.1 mg dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Men and women, 18 years of age and older Signed and dated informed consent to participate before any study-related procedures are performed Diagnosis of Crohn's disease for at least 6 months that has been documented and confirmed A Crohn's Disease Activity Index (CDAI) score of 220 to 450 inclusive Female subjects who are not surgically sterile or postmenopausal must use medically acceptable methods of birth control during and for 30 days after the treatment period. HCT 30% or greater WBC 3.5 x 109/L or greater Platelets 100 x 109/L or greater Adequate renal function defined as: serum creatinine and BUN 1.5 x ULN or less Adequate hepatic function defined as: ALT/SPGT, AST/SGOT 2.0 x ULN or less; total bilirubin 1.25 x ULN or less, alkaline phosphatase 1.5 x ULN or less Female subjects of childbearing potential must have negative urine pregnancy test results prior to randomization A stool sample must be taken at screening and analyzed by a local laboratory for enteric pathogens, pathogenic ova and parasites, and Clostridium difficile toxin, and reported negative prior to randomization. C-reactive protein value must be 1.0 mg/dL or more, unless there are obvious manifestations of currently active Crohn's disease such as positive observations on endoscopy, other positive indications by laboratory test results, or the subject has had a previous intestinal resection for Crohn's disease. Exclusion Criteria Nutritionally compromised subjects requiring enteral or parenteral therapy to maintain weight Body weight less than 40 kg or more than 100 kg Bowel obstruction or any condition that may predispose to its development, intestinal perforation, or significant gastrointestinal hemorrhage Current ileostomy or colostomy or extensive external fistulization (more than 3 external fistulae which are expressible with gentle compression) Expected to require surgical therapy for Crohn's disease or Crohn's disease related complications within 12 weeks of screening. If an abscess is present, it should be drained at least 3 weeks before pre-screening History of ulcerative colitis within 6 months of screening visit Cushing's syndrome Known HIV infection, or symptoms or signs of HIV infection Acute systemic infection and/or intestinal infection requiring antibiotic therapy at time of screening or baseline Evidence of chronic hepatitis B or C viral infection Decompensated liver disease Clinically significant ECG abnormalities History of angina or cardiac arrhythmia requiring drug or device intervention or clinically significant congestive heart failure or other clinically significant cardiac disease History of myocardial infarction within 12 months of screening History of thromboembolic disease (e.g., phlebitis, pulmonary embolus) or known congenitally or acquired prothrombotic disorder (e.g., protein C deficiency) History of cancer (other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer) or clinically significant lymphoproliferative disease with fewer than 5 years documented disease-free state Known substance abuse in the previous 2 years Nursing mothers or pregnant women Use of native GLP-2, growth hormone, or growth factors within 3 months of signing informed consent Use of any of the prior or concomitant medications described in section 5.4, except as specified Known hypersensitivity to any of the active or inactive constituents of ALX-0600

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo solution injected subcutaneously daily into either thigh or abdomen. | Drug: placebo<br>* placebo solution injected subcutaneously<br>|
| Experimental: teduglutide 0.05<br>teduglutide 0.05 mg/kg/d injected subcutaneously daily. | Drug: Teduglutide 0.05 dose<br>* 0.05 mg/kg/d subcutaneous daily injection into thigh or abdomen<br>* Other names: GATTEX;|
| Experimental: teduglutide 0.1<br>0.1 mg/kg/d teduglutide injected subcutaneously into thigh or abdomen | Drug: teduglutide 0.1 mg dose<br>* 0.1 mg/kg/d daily subcutaneous injection into thigh or abdomen<br>* Other names: GATTEX;|
| Experimental: teduglutide<br>0.2 mg/kg/d teduglutide injected subcutaneously into thigh or abdomen | Drug: ALX-0600<br>* teduglutide<br>* Other names: GATTEX;Drug: teduglutide 0.05<br>* 0.05 mg/jg/d subcutaneous daily injection into thigh or abdomen<br>* Other names: GATTEX;Drug: teduglutide 0.2 mg<br>* 0.2 mg/kg/d subcutaneously injected into thigh or abdomen<br>* Other names: GATTEX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy variable is the percentage of subjects who respond to treatment, defined as the percentage of subjects who are in remission (CDAI less than 150) or have a 100-point or greater reduction from baseline in CDAI score at dosing Week 8. |  | 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The various secondary efficacy variables are based on the CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ), plasma citrulline and laboratory inflammatory markers. |  | 8 weeks of treatment |