Primary ObjectivesPlacebo-Controlled Induction Period: Primary Objective: Compare the proportion of subjects who have a clinical response (as defined by a reduction in Crohn*s Disease Activity Index [CDAI] >= 100 or an absolute CDAI score <…
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Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Placebo-controlled Induction Period:
Compare the proportion of subjects who have a clinical response (as defined by
a reduction in Crohn*s Disease Activity Index (CDAI) >= 100 or an absolute CDAI
score < 150) at both Day IP-57 (Week 8) and Day IP-85 (Week 12) between the
abatacept and placebo treatment regimens.
Maintenance Period:
Compare the proportion of subjects who are in clinical remission (as defined by
a CDAI < 150) at Day MP-365 (12 months) between the abatacept and placebo
treatment regimens.
Open-Label Extension Phase:
Assess the long-term clinical safety and tolerability of abatacept treatment
during the Open-label Extension Phase.
Secondary outcome
Secondary Objectives: Placebo-controlled Induction Period
1) Compare the proportion of subjects who are in clinical remission (as defined
by an absolute CDAI score < 150) at both Day IP-57 and Day IP-85 between the
abatacept and placebo treatment regimens.
2) Evaluate the dose-response relationship by comparing the proportions of
subjects who have a clinical response at both Day IP-57 and Day IP-85 induced
by placebo and abatacept in increasing doses (3 mg/kg, ~10 mg/kg, 30/~10
mg/kg).
3) Assess improvements in quality of life at Day IP-85 and using the
Inflammatory Bowel Disease Questionnaire (IBDQ) in abatacept vs. placebo
treated subjects.
4) Assess the tolerability and safety of abatacept in subjects with CD.
5) Assess the immunogenicity of abatacept in subjects with CD.
6) Evaluate in subjects who have had an inadequate response and/or intolerance
to anti-TNF therapy, the dose-response relationship by comparing the
proportions of subjects in clinical response at Day IP-85 induced by placebo
and abatacept in increasing doses (3 mg/kg, ~10 mg/kg, 30/~10 mg/kg).
7) Assess in abatacept vs placebo treated subjects who have had an inadequate
response and/or intolerance to anti-TNF therapy, a) the proportion in clinical
response, and b) the proportion in clinical remission, at both Day IP-57 and
Day IP-85.
For the Secondary Objectives for the Maintenance Period and Open-Label
Extension Phase, please refer to pages 26-28 of the protocol.
Background summary
Crohn's Disease (CD) is a severe disorder with significant morbidity and impact
on quality of life. Despite the availability of a range of medications, there
still remains a need for therapeutic alternatives because patients may not
respond to existing therapeutic choices, may not maintain a response, or may
develop treatment limiting toxicities. Abatacept has the potential to be an
effective and safe alternative to those therapies. The intended application of
the results from this study is to prove that abatacept is effective and safe
for the treatment of patients with active Crohn*s Disease with a view to
obtaining a marketing license for this indication.
Study objective
Primary Objectives
Placebo-Controlled Induction Period: Primary Objective: Compare the proportion
of subjects who have a clinical response (as defined by a reduction in Crohn*s
Disease Activity Index [CDAI] >= 100 or an absolute CDAI score < 150) at both
Day IP-57 (Week 8) and Day IP-85 (Week 12) between the abatacept and placebo
treatment regimens.
Maintenance Period: Primary Objective: Compare the proportion of subjects who
are in clinical remission (CDAI < 150) at Day MP-365 (12 months) between the
abatacept and placebo treatment regimens.
Study design
The study consists of three periods (Screening, Induction, and Maintenance) and
an Open-Label Extension phase. Following the Screening Period, eligible
subjects will enter a 12-week Induction Period (IP). A first cohort of 469
subjects will be randomized to the IP in a 2:1:2:2 fashion to receive placebo
or one of three doses of abatacept (3 mg/kg, ~10 mg/kg, or 30/~10 mg/kg) in a
double-blind manner. Following the randomization of the initial cohort of 469
subjects, a second cohort of 120 subjects will be randomized to the IP to one
of two dosing regimens of abatacept (~10 mg/kg or 30/~10 mg/kg) in a
double-blind 1:1 manner. All subjects who meet protocol-defined response at the
end of the IP will then enter a 12-month randomized double-blind
parallel-dosing, placebo-controlled Maintenance Period (MP) where they will be
randomized to ~10 mg/kg abatacept or placebo. It is anticipated that
approximately 334 subjects will enter the MP. Subjects who complete the IP but
do not meet response criteria at Day IP-85 and subjects who complete the MP or
who relapse during the MP may enter an Open-label Extension phase (OL).
Intervention
Abatacept will be administered IV. Induction Period: Days IP-1 and IP-15,
subjects assigned to abatacept will receive 3 mg/kg (fixed dose), ~10 mg/kg
dose (weight-tiered), or 30 mg/kg doses (fixed dose). On Days IP-29 and IP-57,
subjects assigned to receive abatacept will receive 3 mg/kg or ~10 mg/kg dose.
After entering the Maintenance Period, subjects assigned to abatacept, will
receive ~10mg/kg every 28 days up to and including Day MP-337. In the
Open-label Extension, all subjects receive open-label ~10mg/kg every 28 days.
Study burden and risks
The major identified risk of abatacept is an increased incidence of infection.
Consistent with its mechanism of action, the abatacept RA program identified
both non-serious and serious infections, mainly bacterial (urinary tract
infections, pneumonia) and viral (herpes simplex) occurring more frequently in
abatacept-treated subjects. Despite this identified risk, the majority of
infections presented typically, responded appropriately to treatment, and there
did not appear to be a major difference in outcome between abatacept and
placebo. The risk for serious infections did not increase in the open-label
periods with increasing exposure. Opportunistic infections and tuberculosis
were uncommon, although all subjects were screened for latent TB. The overall
risk of malignancy for abatacept-treated subjects was comparabale with
placebo-treated subjects during the double-bllind periods. The incidence of
malignancy did not appear to be greater with increased exposure. An important
caution is that the clinical studies contain neither sufficient numbers of
subjects nor follow up of sufficient duration to assess long term treatment or
to rule out increases in the risk of adverse events with long latency, such as
malignancy. Treatment with abatacept was associated with an excellent
peri-infusional safety profile, and abatacept was associated with a low level
of immunogenicity.
Vijzelmolenlaan 9
3447 GX Woerden
NL
Vijzelmolenlaan 9
3447 GX Woerden
NL
Listed location countries
Age
Inclusion criteria
1) Subject is willing to participate in the study and has signed the informed consent
2) Subject must have had CD for at least 3 months from the time of initial diagnosis. Active CD must be confirmed by radiologic, endoscopic or histologic evidence within the previous 12 months. If previous confirmation of diagnosis is not available or if previous diagnosis is not deemed conclusive at time of screening, CD diagnosis should be confirmed by endoscopy, radiology or histology.
3) Subjects must satisfy at least one of the following criteria:
a) Having had an inadequate response to at least 1 of the following treatments (subjects may be currently receiving 1 of these medications or have received them previously):
i) oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalizide) at or above the approved label dose for at least 8 weeks and/or
ii) oral prednisone >= 30 mg/day (or equivalent) or budesonide >= 9 mg/day for at least 4 weeks and/or
iii) immunosuppressants (azathioprine >= 2 mg/kg/day or 6-mercaptopurine >= 1.0 mg/kg/day [or documentation of a therapeutic concentration of 6 thioguanine nucleotide] or methotrexate >= 15 mg/week) for at least 12 weeks and/or
iv) an approved anti-TNF agent at an approved labeled dose for at least 8 weeks
AND/OR
b) Have been intolerant to one of the above mentioned treatments (e.g., unable to achieve doses or treatment durations because of dose limiting side effects [e.g., leukopenia]).
4) Moderate to severe CD as measured by a CDAI score >= 220 and <= 450
5) hsCRP > Upper Limit of Normal (ULN)
6)Men and women, ages >=18
Exclusion criteria
1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the study
2) WOCBP using a prohibited contraceptive method (there are no prohibited methods for this study)
3) Women who are pregnant or breastfeeding
4) Women with a positive pregnancy test on enrollment or prior to study drug administration
5) Diagnosis of Ulcerative or Indeterminate Colitis
6) CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic or ileal involvement
7) Suspected or diagnosed intra-abdominal or perianal abscess at screening
8) Known strictures or stenosis leading to symptoms or obstruction
9) Current evidence of fulminant colitis, toxic megacolon or bowel perforation
10) Subjects who are scheduled or anticipate the need for surgery, aside from dermatologic procedures
11) Subjects who have a history of clinically significant drug or alcohol abuse
12) Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, pulmonary, cardiac, neurological, ophthalmologic or cerebral disease. Concomitant medical conditions that in the opinion of the Investigator might place the subject at unacceptable risk for participation in this study
13) Subjects with a history of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to enrollment. Subjects with carcinoma in situ, treated with definitive surgical intervention, are allowed
14) Subjects at risk for tuberculosis (TB).
15) Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any chronic bacterial infection (such as chronic pyelonephritis, osteomyelitis and bronchiectasis)
16) Female subjects who have had a breast cancer screening that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations
17) A history of severe or anaphylactic infusion reaction after receiving a biologic agent, suspected to be associated with an immune response
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 | EUCTR2006-003371-13-NL |
| CCMO | NL15361.058.07 |