To demonstrate the efficacy of adalimumab on mucosal healing in subjects with moderate to severe ileocolonic Crohn's disease and to delineate the safety of adalimumab when administered to subjects with Crohn's disease.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is the presence or absence of mucosal ulceration
by endoscopy. The primary outcome analysis will be a comparison of the
proportions of subjects without mucosal ulceration on endoscopy in the
adalimumab and placebo groups at Week 12.
Secondary outcome
Secondary efficacy variables will be:
- Crohn's Disease Endoscopic Index of Severity (CDEIS) scores,
- the Simple Endoscopic Score for Crohn's Disease (SES-CD) and ulcer counts
- CDAI score
- number of subjects discontinued from steroids
- total IBDQ scores
- WPAI scores
- SF * 36
- dimension scores
- Unscheduled Outpatient Visits
- Emergency Room Visits
- Hospitalizations Questionnaire
Background summary
Despite the current treatment options for Crohn*s disease a lot of patients
still do experience Crohn*s disease symptoms. There is evidence for the
efficacy of TNF antagonists in treating patients with Crohn*s disease.
After a while a large number of the patients do no longer tolerate the
treatment, become allergic or don*t respond because antibodies are formed.
Adalimumab is an almost fully human and this adverse reaction is not expected.
Adalimumab can be administered at home unlike TNF therapies currently used. In
this trial will the efficacy of Adalimumab on mucosal healing in subjects with
moderate to server ileocolonic Crohn*s be compared to a placebo. The results
will be of importance to compare the efficacy of Adalimumab to existing
anti-TNF therapies. It is expected that Adalimumab works just as good but
without intolerance, allergy or non-responce.
Study objective
To demonstrate the efficacy of adalimumab on mucosal healing in subjects with
moderate to severe ileocolonic Crohn's disease and to delineate the safety of
adalimumab when administered to subjects with Crohn's disease.
Study design
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study
Intervention
Study medication will be administered by sc injection. At Baseline (Week 0),
all subjects will receive an open-label dose of 160 mg adalimumab. At Week 2,
all subjects will receive an open-label dose of 80 mg adalimumab. At Week 4,
all subjects will be randomized to receive injections of adalimumab 40 mg eow
or placebo eow. At page 17 of the study protocol is a schematic overview of
the study medication dosing.
Study burden and risks
The subject will participate in the trial for a maximum period of 52 weeks.
During this period will the subject the visit hospital 13 times. At the
discretion of the investigator can additional visits be planned. 70 days after
the last visit will the subject contacted by telephone.
A full physical examination will be performed during the screening visit. The
subject may experience some bruising and/or slight soreness, and possible
infection or bleeding at the blood collection site. The patient may also
develop fainting or dizziness after the blood sample is taken.
The subject will be asked to keep a dosing sheet and an adverse event log. The
subject will be asked 5 times to complete 3 questionnaires.
The subject will undergo an endoscopy for a maximum of 4 times. During this
endoscopy will a biopt be taken. Depending on the instructions preparation for
the endoscopy may involve a limitation on the kinds of food the subject may eat
for 1-2 days prior to the test. Preparation for the endoscopy may also involve
the use of laxatives that may produce loose stools. Possible risks during the
endoscopy are getting a puncture (or hole) in the colon wall, which may require
surgery to correct, and bleeding that requires getting blood from donors. The
risk of the sedation medication, usually given during an endoscopy to help you
relax, may cause allergic reactions such as nausea, skin rash, dizziness with a
drop in blood pressure, a slowing down of your breathing so much that in very
rare cases a breathing machine will be used, and death from sedation-related
heart problems. These risks are small, fewer than 1 in 100 subjects.
During x-rays of the chest the subject will be exposed to a small amount of
radiation. The amount of radiation is not considered a significant risk.
While using the study medication the subject may experience adverse reactions.
The adverse reactions most often reported when comparing subjects on Adalimumab
to placebo (injection with no active drug) the following side effects were more
frequent in Adalimumab group and occurred at a rate of >= 5%: upper
respiratory infection, headache, rash, sinusitis, accidental injury, nausea,
abdominal pain, back pain, urinary tract infection, hypertension and flu
syndrome.
Women of childbearing potential have to use an effective method of birth
control as described in the study protocol.
The use of some medication is not allowed for subjects participating in the
trial. This medication is described in the protocol.
Knollstr. 50
67061 Ludwigshafen
Germany
Knollstr. 50
67061 Ludwigshafen
Germany
Listed location countries
Age
Inclusion criteria
1. Diagnosis of Crohn's Disease for greater than 4 months.
2. A diagnosis of ileocolonic Crohn's Disease confirmed by endoscopy or radiologic evaluation within 3 years of Baseline.
3. For subjects that have had operations in the ileocolonic region of the intestine after documented diagnosis of ileocolonic disease, postoperative recurrence of the disease must be documented.
4. Endoscopic documentation of ulceration at Screening corresponding to a score of 2 or 3 on the Ulcerated Surface subscore of the SES-CD.
5. Crohn's Disease Activity Index (CDAI) score of ><= 220 and <<= 450.
6. Males and females ><= 18 and ><= 75 years of age at the Baseline visit.
7. Subjects must be able to self-inject study medication or have a designee or healthcare professional who can inject the study medication.
8. Subjects must agree to undergo up to 4 endoscopies.
Exclusion criteria
1. History of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma in-situ of the cervix.
2. History of listeria, human immunodeficiency virus (HIV), Hepatitis B, an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease or untreated TB.
3. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the investigator and Abbott Medical Monitor.
4. Subject who has had surgical bowel resections within the past 6 months or is planning any resection at any time point while enrolled in the study.
5. Subject with an ostomy or ileoanal pouch. (Subjects with a previous ileo-rectal anastomosis are not excluded).
6. Subject who has previously used infliximab or any anti-TNF agent and has not clinically responded.
7. Previous treatment with adalimumab or previous participation in an adalimumab clinical study.
8. Subjects on prednisone >40 mg/day (or equivalent).
9. Subjects on budesonide >9 mg/day.
10. Subjects with any prior exposure to Tysabri® (natalizumab).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2005-005291-32-NL |
| CCMO | NL12174.018.06 |