Celgene CD-002 (SMAD 7)

Principal Investigator: John  Valentine
Keywords: Crohns , SMAD 7 , GED-0301-CD-002 Department: Gastroenterology
IRB Number: 00095318 Co Investigator:  
Specialty: Gastroenterology
Sub Specialties: Inflammatory Bowel Disease/Crohn's/Ulcerative Colitis
Recruitment Status: Recruiting

Contact Information

Julie Will
julie.will@hsc.utah.edu
801-587-9060

Brief Summary

Purpose
The purpose of this Phase 3 study is to demonstrate the efficacy and safety of GED-0301 in
subjects with active CD to support its registration for the indication of the treatment of active
CD. Active CD is defined as a CDAI score ≥ 220 and ≤ 450 at screening and a total Simple
Endoscopic Score for Crohn's Disease (SES-CD) ≥ 6 at screening, or the ileum segmental SESCD
≥ 4 at screening. Subjects must have failed or experienced intolerance to at least one of the
following: budesonide; systemic corticosteroids; immunosuppressants (eg,
azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]); or biologics (ie,
infliximab, adalimumab, certolizumab or vedolizumab).
 
Primary Objective
The primary objective of the study is to evaluate the efficacy of GED-0301 compared with placebo on
clinical activity, at week 12 in subjects with active Crohn’s disease (CD).
 
Secondary Objectives
The secondary objectives are:
-To evaluate the efficacy of GED-0301 compared with placebo on endoscopic outcomes,in subjects with active CD
-To evaluate the long-term efficacy of GED-0301 compared with placebo on clinical activity in subjects with active CD
-To evaluate the efficacy of GED-0301 compared with placebo on corticosteroid-free clinical
remission in subjects with active CD;
-To evaluate the safety and tolerability of GED-0301 in subjects with active CD.
 
Exploratory Objectives
The exploratory objectives are:
-To evaluate additional measures of short-term and long-term efficacy of GED-0301 compared
with placebo on clinical activity and endoscopic outcomes in subjects with active CD;
-To evaluate the change in biomarkers such as high sensitivity C-reactive protein (hsCRP) and
fecal calprotectin (FCP) in response to GED-0301, compared with placebo, in subjects with
active CD;
- To evaluate the change in quality of life and health economic outcomes in response to GED-0301,
compared with placebo, in subjects with active CD;
-To evaluate the systemic exposure of GED-0301 in subjects with active CD.

Inclusion Criteria

Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is a male or female ≥ 18 years at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to conducting any studyrelated
assessments/procedures.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject must have a diagnosis of CD with a duration of at least 3 months prior to the
Screening Visit.
5. Subject must have a diagnosis of ileitis, ileocolitis or colitis, as determined by ileocolonoscopy during screening.
6. Subject must have active CD disease, defined as a CDAI score ≥ 220 and ≤ 450 at screening.
7. Subject must have a 7-day average stool frequency ≥ 3.5 or abdominal pain ≥ 1.5 at screening.
8. Subject must have a total SES-CD ≥ 6 at screening, or the ileum segmental SES-CD ≥ 4
at screening.
9. Subject must have failed or experienced intolerance to at least one of the following:
budesonide; systemic corticosteroids; immunosuppressants (eg, AZA, 6-MP, or MTX); or biologics for the treatment of CD (ie, infliximab, adalimumab, certolizumab or vedolizumab). (See Appendix H for details.)
10. Subject must meet the following laboratory criteria
a. White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L)
b. Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
c. Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
d. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x upper limit of normal (ULN)
e. Total bilirubin ≤ 2 mg/dL (34 μmol/L), unless the subject has a confirmed diagnosis of Gilbert’s Disease
f. Hemoglobin ≥ 8 g/dL (≥ 4.97 mmol/L)
g. Activated partial thromboplastin time (APTT) ≤ 1.5 x ULN
11. Females of childbearing potential (FCBP)1 must have a negative pregnancy test at the
Screening and Baseline Visits. While on IP and for at least 28 days after taking the last
dose of IP, FCBP who engage in activity in which conception is possible must use one of
the approved contraceptive options described below:
Option 1: Any one of the following highly effective methods: hormonal
contraception (oral2, injection, implant, transdermal patch, vaginal ring); intrauterine
device (IUD); tubal ligation; or partner’s vasectomy
OR
Option 2: Male or female condom PLUS 1 additional barrier method: (a) diaphragm
with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with
spermicide
 
1 A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months).
2 A female of childbearing potential taking an oral contraceptive may need a backup or an alternative method of birth control based on Investigator judgment as the subject’s Crohn’s disease may potentially decrease the effectiveness of oral contraceptives.
 

Exclusion Criteria

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

1. Subject has a diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic colitis,
microscopic colitis, radiation colitis or diverticular disease-associated colitis.
2. Subject has local manifestations of CD such as strictures, abscesses, short bowel syndrome, or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy.
3. Subject had any intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit.
4. Subject has an ileostomy or a colostomy.
5. Subject had prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine,
thalidomide or apheresis (eg, Adacolumn®) within 8 weeks prior to the Screening Visit.
6. Subject has received IV corticosteroids within 2 weeks prior to the Screening Visit.
1 A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months).
7. Subject has changed or discontinued the allowed dose of oral aminosalicylates within 2 weeks prior to the Screening Visit.
8. Subject has changed or discontinued the allowed dose of oral corticosteroids (prednisone ≤ 20 mg/day or equivalent, budesonide ≤ 9 mg/day) within 3 weeks prior to the Screening Visit.
9. Subject has initiated immunosuppressants (eg, AZA, 6-MP, or MTX) within 12 weeks prior to the Screening Visit and has changed or discontinued the allowed dose of immunosuppressants within 8 weeks prior to the Screening Visit.
10. Subject has received topical GI treatments, such as, 5-aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks prior to the Screening Visit.
11. Subject has received bile acid sequestrants (eg, cholestyramine) within 3 weeks prior to the Screening Visit.
12. Subject has changed or discontinued antibiotics used for the treatment of CD (eg, ciprofloxacin, metronidazole), within 2 weeks prior to the Screening Visit.
13. Subject had prior treatment with more than 3 biologics for the treatment of CD.
(ie,infliximab, adalimumab, certolizumab or vedolizumab).
14. Subject had treatment with a biologic within 8 weeks or 5 elimination half lives, whichever is longer, prior to the Screening Visit.
15. Subject has received total parenteral nutrition within 4 weeks prior to the Screening Visit.
16. Subject has evidence of enteric infection or Clostridium C.- difficile toxin at the Screening Visit.
17. Subject has a history of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the Investigator's opinion, would prevent the subject from participating in the study.
18. Subject has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study.
19. Subject is pregnant or breastfeeding.
20. Subject has a history of any of the following cardiac conditions within 6 months prior to
the Screening Visit and at any time during the Screening Period, up through the first
dose of IP: myocardial infarction, acute coronary syndrome, unstable angina, new onset
atrial fibrillation, new onset atrial flutter, second- or third-degree atrioventricular block,
ventricular fibrillation, ventricular tachycardia, heart failure, cardiac surgery,
interventional cardiac catheterization (with or without a stent placement), interventional
electrophysiology procedure, or presence of implanted defibrillator.
21. Subject has a known active current or history of clinically significant, recurrent
bacterial, viral, fungal,  or other infections, or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to the Screening Visit and at any time during the Screening Period, up through the first dose of IP.
22. Subject has a history of congenital or acquired immunodeficiency (eg, common variable
immunodeficiency disease).
23. Subject has a history of colorectal cancer or confirmed diagnosis colorectal dysplasia (with the exception of adenomatous colonic polyps that have been completely resected).
24. Subject has a history of malignancy, except for:
a. Treated (ie, cured) basal cell or squamous cell in situ skin carcinomas
b. Treated (ie, cured) cervical intraepithelial neoplasia or carcinoma in situ of the
cervix with no evidence of recurrence within the previous 5 years prior to the Screening Visit
25. Subject has received any investigational drug or device within 1 month or 5 elimination half-lives
whichever is longer, prior to the Screening Visit.
26. Subject has a history of alcohol, drug, or chemical abuse within the 6 months prior to the
Screening Visit.
27. Subject has a known hypersensitivity to oligonucleotides or any ingredient in the IP.
28. Subject has received prior treatment with GED-0301, or participated in a clinical study
involving GED-0301.
29. Subject has strictures with prestenotic dilatation, requiring procedural intervention, or
with obstructive symptoms. In addition, subjects with colonic strictures that are not
passable with an adult colonoscope, or strictures in the ileum or ileocecal valve that are
fibrotic in nature, will be excluded.
30. Subject had prior treatment with biologics for the treatment of CD (approved or
investigational), other than infliximab, adalimumab, certolizumab or vedolizumab.