The purpose of this study is to evaluate the safety and effectiveness of adalimumab for the treatment of moderate to severe Crohn*s disease in children between 6-17 years of age. In addition, information will be collected to select the most…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is the proportion of subjects who are in clinical
remission at Week 26. Clinical remission is defined as PCDAI score > 10.
Secondary outcome
Major secondary efficacy endpoints are:
- proportion of subjects in PCDAI clinical remission at Week 52
- proportion of subjects in PCDAI clinical response at Week 26 and in week 52
- proportion of subjects receiving corticosteroid at Baseline who have
discontinued corticosteroid for at least 90 consecutive days prior to Week 26
and are in PCDAI clinical remission at Week 26
- change from Baseline in *z*- scores (for height velocity) at Week 26
- change from Baseline in total IMPACT III scores at Week 26.
protocol p57
Background summary
While adalimumab was approved for the treatment of adult Crohn*s disease in the
United States on 27 Feb 2007, in the European Union on 04 Jun 2007, and in
Canada on 05 Jul 2007, it is still being tested in subjects with moderate to
severe Crohn*s disease.
Adalimumab is made in the laboratory and is identical to a natural human
antibody. Adalimumab is believed to work by blocking the inflammatory process,
thus helping to relieve the signs and symptoms of Crohn*s disease.
Your child has Crohn*s disease and is currently being treated. Despite this
treatment, your child is still experiencing signs and symptoms of Crohn*s
disease (for example: stomach pain, diarrhea, and fatigue). It is believed that
adalimumab may help patients with Crohn*s disease who have not had complete
relief of their symptoms with currently available medications.
This study is sponsored by Abbott Laboratories and is being conducted at
approximately 55 treatment centers in the United States, Canada and Europe.
Approximately 184 children with Crohn*s disease will participate in this
study for up to 55 weeks.
Study objective
The purpose of this study is to evaluate the safety and effectiveness of
adalimumab for the treatment of moderate to severe Crohn*s disease in children
between 6-17 years of age. In addition, information will be collected to select
the most effective dose of adalimumab.
Study design
At the start of the study, all subjects will receive an open-label induction
dose of adalimumab. If the child weighs greater than or equal to 40 kg at the
Baseline study visit, he/she will receive an initial dose of 160 mg
adalimumab (4 shots of 40 mg) at baseline and 80 mg adalimumab (2 shots of 40
mg) at Week 2. If the child weighs less than 40 kg at the Baseline study
visit, he/she will receive an initial dose of 80 mg adalimumab (2 shots of 40
mg) at baseline (week 0) and 40 mg adalimumab (1 shot of 40 mg) at Week 2.
These induction doses will be followed by blinded treatment of adalimumab every
other week from Week 4 through Week 52. There are two dosing groups of
adalimumab that are being tested in this study, a high dose and a low dose
depending on the child*s weight at the Week 4 study visit. The child will be
selected by chance.
If the child weighs less than 40 kg, he/she will either receive 20 mg
adalimumab every other week or 10 mg adalimumab every other week beginning from
Week 4. If the child weighs greater than or equal to 40 kg, he/she will
either receive 40 mg every other week or 20 mg every other week beginning from
Week 4.
If at or after Week 12 the child*s Crohn*s disease becomes more active or
he/she does not respond to treament, the study medication can be changed to
weekly injections of the same adalimumab dose. Following 8 weeks of every week
blinded dosing, if the child*s Crohn*s disease becomes more active or does not
respond to treatment, the study medication may be changed to open-label
adalimumab.
If the child*s body weight has increased from below 40 kg to above 40 kg at
Week 26, then the dose of study medication will be increased.
If the child does complete the study he/she can participate in the open-label
extension study.
see protocol p21
Intervention
The patients will have a subcutaneous injection every other week. In case of
non-response or flare this can be changed in weekly injections from week 12 on.
Study burden and risks
Before treatment is started, the child would undergo some tests and
examinations during a screening period to be sure that he/she meets the study
entry requirements and that it is safe for him/her to enter the study. During
this screening period, the child*s medical history will be reviewed and several
medical examinations performed.
During the study, the child will visit the study doctor at screening, baseline,
Week 2; 4; 8; 12; 16; 20; 26; 32; 40; 48 and 52.
At all visits your child will undergo vital sign measurements, a physical exam,
clinical assessment, and have a urine test and blood test performed.
Approximately 9 mls-17 mls of blood will be drawn at each of these visits. At
some visits, up to 35 mls of blood will be collected.
If the child is 13 years of age or older at the baseline visit, he/she will be
required to take a card home and record the number of bowel movements he/she
has in a day, how much pain he/she are experiencing, and rate his/her
general well being. The child will also be asked to complete a card to record
information about any new medications or any changes in medication your child
takes on an ongoing basis throughout the study.
At every study visit the child will be asked about any side effects he/she is
experiencing, problems he/she are having.
Subjects > 10 years old at Baseline will complete an IMPACT III questionnaire
about his/her health at Baseline, Week 12, Week 26, and Week 52/ Early
Termination visits. At every visit the parent/guardian, will be asked to
complete one questionnaire on the impact of the child*s Crohn*s disease on
his/her day to day activities.
Eventual risks: zie section E9.
Knollstrasse 50
67061 Ludwigshafen
Duitsland
Knollstrasse 50
67061 Ludwigshafen
Duitsland
Listed location countries
Age
Inclusion criteria
Main Inclusion:
1. Subjects between the ages of 6 and 17, inclusive prior to baseline dosing.
2. Subjects with a diagnosis of Crohn*s disease for greater than 12 weeks prior to screening confirmed by endoscopy or radiologic evaluation.
3. Subjects with a PCDAI score of >30.
4. Parent or guardian has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject*s parent or legal guardian has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed or before any medication is discontinued for the purpose of this study. Pediatric subjects will be included in all discussions in order to obtain verbal or written assent.
5. Parent or legal guardian must be willing to actively supervise storage and administration of study drug and to ensure that the time of each dose is accurately recorded in the subject*s diary.
6. Adequate cardiac, renal and hepatic function as determined by principal investigator and demonstrated by Screening laboratory evaluations, questionnaires, and physical examination results that are within normal limits.
7. Subjects may have previously received infliximab providing the subject had an initial response and then discontinued use due to a loss of response or discontinued use due to intolerance.
Exclusion criteria
Main Exclusion:
a. 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.
b. History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus (HIV), an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease, or active TB (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections.
c. Subject with infectious colitis, ulcerative colitis or indeterminate colitis as determined by the investigator and Abbott Medical Monitor.
d. Subject who has had surgical bowel resections within the past 24 weeks or is planning any resection at any time point while enrolled in the study.
e. Subject with an ostomy or ileoanal pouch. (Subjects with a previous ileo-rectal anastomosis are not excluded).
f. Females who are pregnant or are currently breast-feeding.
g. Subject with a history of clinically significant drug or alcohol abuse in the last year.
h. Subjects with a poorly controlled medical condition such as: uncontrolled diabetes mellitus, moderate to severe heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator or the sponsor, would put the subject at risk by participation in the protocol.
i. Subjects on azathioprine, 6-MP, or MTX who have not been on these medications for at least eight weeks prior to Baseline and on stable doses of these medications for at least four weeks prior to Baseline. Subjects who have been on azathioprine, 6-MP, or MTX who have discontinued these medications within 8 weeks of Baseline.
j. Subjects on aminosalicylates, or Crohn's-related antibiotics (fluoroquinolones such as ciprofloxacin or nitroimidazole derivatives such as metronidazole) who have not been on stable doses of these medications for at least four weeks prior to Baseline. In addition, subjects on aminosalicylates or Crohn's-related antibiotic treatments who have discontinued these medications within four weeks of Baseline.
k. Subjects on Growth Hormone who have not been on a stable dose for at least 12 weeks prior to Baseline. Subjects must consent to remain on a stable dose through the duration of the study.
l. Subjects on prednisone > 40 mg/day (or equivalent) or subjects on < 10 mg/day prednisone or budesonide > 9 mg/day and subjects who were not on stable doses for at least 2 weeks prior to Baseline. In addition, subjects who discontinued either corticosteroid within 2 weeks of Baseline. Subjects taking both budesonide and prednisone (or equivalent) are excluded.
m. Subject who has previously used infliximab within 8 weeks of Baseline.
n. Previous treatment with adalimumab or previous participation in an adalimumab clinical study.
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 | EUCTR2006-004814-41-NL |
| CCMO | NL21165.078.08 |