Evaluate the Safety, Tolerability, and Efficacy of AMG 827 in Subjects with Moderate to Severe Crohn*s Disease.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the efficacy of AMG 827 compared with placebo as measured by the
proportion of subjects achieving Crohn*s Disease Activity Index (CDAI)
remission ( * 150) at week 6.
Secondary outcome
* To evaluate the efficacy of AMG 827 as measured by the proportion of subjects
with a CDAI response (reduction from baseline of * 100) at week 6
* To evaluate improvement from baseline in CDAI at week 6
* To evaluate the short term safety profile of AMG 827 in subjects with Crohn*s
disease
* To characterize the pharmacokinetics (PK) of AMG 827 in subjects with Crohn*s
disease
Background summary
Crohn*s disease is a chronic relapsing, remitting inflammatory disease of the
gastrointestinal tract although some patients may have continuously active
disease. The cause of Crohn*s disease remains unknown.
Crohn*s disease affects the gastrointestinal tract discontinuously from mouth
to anus, but most commonly the disease is located both in the ileum and colon,
small bowel only, or colon only. Crohn*s occurs in all age groups with a
higher incidence in the younger population; there is no marked sex difference.
The incidence of Crohn*s disease in adults has been reported as up to
approximately 8 per 100,000 person-years, with the highest reported adult-onset
incidences in Spain (Saro Gismera et al, 2000), Sweden (Lapidus, 2006), and the
United Kingdom (García Rodríguez et al, 2005).
Studies have found increased mortality in patients with Crohn*s disease
(Duricova et al, 2009), as well as a negative impact to their daily life.
Medical therapy used in clinical practice includes aminosalicylates,
corticosteroids, immunomodulators, antibiotics, and biologic therapies with
nutritional support also having a role (Lichtenstein et al, 2009). When
medical treatment is unsuccessful or with certain complications, surgery is
indicated. Due to therapeutic failures and serious side effects of present
therapies, alternatives are needed.
AMG 827 is a fully human IgG2 anti-interleukin-17 receptor (IL-17R) monoclonal
antibody that selectively targets human IL-17R and antagonizes the IL-17
pathway. It binds with high affinity to human IL-17R and blocks the biological
activity of IL-17 (IL 17A), IL-17F and IL-25 (IL-17E).
Study objective
Evaluate the Safety, Tolerability, and Efficacy of AMG 827 in Subjects with
Moderate to Severe Crohn*s Disease.
Study design
This is a randomized, double-blind, placebo-controlled study to evaluate the
efficacy of AMG 827 (at intravenous [IV] infusion doses of 210, 350 or 700 mg)
compared with placebo as measured by the proportion of subjects in remission
(CDAI * 150) at week 6. After completing all screening assessments and meeting
all eligibility criteria, subjects will be randomized in a 1:1:1:1 ratio to
receive AMG 827 210 mg, 350 mg, or 700 mg, or placebo IV infusion at baseline
and week 4. Randomization will be stratified to assure treatment balance in
the PK substudy.
Subjects will be followed through week 12 for assessments of safety and
sustainability of response.
Intervention
Subjects will receive AMG 827 210 mg, 350 mg or 700 mg, or a matching placebo,
at day 1 and week 4 (randomized in a 1:1:1:1 ratio at the baseline visit).
Investigational Product will be administered as an IV infusion over at least 30
minutes.
Study burden and risks
After screening, the patient should visit the hospital for another 6 times. The
average estimated duration of every visit is 2 hours. Subjects participating in
the PK sub study (60 from the 216 globally) will visit the site 3 times in
addition (very short) visits for blood collections. If at week 2 ANC is <1500
cells uL, the subject does need to do an extra visit for an additional blood
collection. The riscs for the participating patient are minimal. The infusion
with AMG 827 or placebo and the blood collections may involve some risks. But,
administration of medication and blood collections will only be done by trained
and experienced personnel; the involved risks will there fore be minimized. If
a subject is PPD positive and there is no thorax X-ray available witiin 3
months before first IP administration, a thorax X-ray does need to be done.
However, the radiation exposure will be very minimal (0.1 mSv). AMG 827 is an
experimental drug. The patient could may experience side effects as mentioned
in the answer to question E9; in addition, the patient also may experience side
effects which are unknow at this moment. The patients recieving AMG 827 may
benefit from the treatment, which may result in a (earlier) remission.
Minervum 7061
4800 DH Breda
Nederland
Minervum 7061
4800 DH Breda
Nederland
Listed location countries
Age
Inclusion criteria
4.1.2 Subject is * 18 and * 65 years of age at time of screening.
4.1.3 Subject has diagnosed ileal, ileo-colonic, or colonic Crohn*s disease for a minimum of 6 months prior to initiating IP.
4.1.4 Subject has moderately to severely active Crohn*s disease, as defined by a CDAI score * 250 and * 450 at baseline.
4.1.5 Subject has evidence of active inflammation, as demonstrated by at least one of the following:
* Endoscopic evidence of inflammation within 12 weeks prior to initiating IP
* Elevated C-Reactive Protein (CRP) at screening (> ULN as set by central laboratory)
* Fecal calprotectin assay indicative of active inflammation at screening (> ULN as set by central laboratory).
4.1.6 Subjects can be receiving the following treatments but the same dose must be maintained as specified below:
* 5-aminosalicylates, if stable dosage for * 2 weeks prior to initiating IP
* Prednisone or equivalent up to 20 mg/day, if stable dosage for * 2 weeks prior to initiating IP
* Budesonide (up to 6 mg/day), if stable dosage for * 2 weeks prior to initiating IP
* Azathioprine, if stable dosage for * 8 weeks prior to initiating IP
* 6-mercaptopurine, if stable dosages for * 8 weeks prior to initiating IP
* Methotrexate, if stable dosages for * 8 weeks prior to initiating IP
* Oral antibiotics for Crohn*s disease, if stable dosage for * 2 weeks prior to initiating IP.
4.1.7 Subject has a negative test at screening for hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus.
4.1.9 Subject has a negative purified protein derivative (PPD; tuberculin) test within 4 weeks before initiating IP. Tuberculin skin tests are considered positive when they have * 5 mm of induration at 48 to 72 hours after test is placed. Subjects with a positive tuberculin skin test (if * 14 mm of induration) are allowed if they meet all of the following criteria:
* a history of Bacillus Calmette-Guerin vaccination with a negative Quantiferon test in the past year
* no symptoms per tuberculosis worksheet
* a negative chest radiograph
Note: subjects with a history of a positive PPD may refuse a repeat PPD and be allowed to continue screening for tuberculosis as above, if there is a history of Bacillus Calmette-Guerin vaccination
Exclusion criteria
Disease-specific criteria
4.2.1 Subject has short bowel syndrome (defined as requiring oral or parenteral supplemental or total nutrition in order to maintain stable body weight, or more than 100 cm of small bowel resected).
4.2.2 Subject has had stricture with obstructive symptoms within 3 months prior to IP initiation.
4.2.3 Subject underwent bowel surgery within 12 weeks prior to IP initiation.
4.2.4 Subject has an ileostomy and/or colostomy.
4.2.5 Subject has any gastric or intestinal pouch
4.2.6 Subject has ulcerative colitis.
4.2.7 Subject has evidence of an infected abscess.
4.2.8 Subject has bowel perforation or evidence of noninflammatory obstruction during the 6 months prior to IP initiation.
4.2.9 Subject has stool positive for C. Difficile toxin at screening.
Other medical conditions.
4.2.14 Subject has one or more significant concurrent medical conditions, including:
* Diagnosis of type 1 diabetes
* Hemoglobin A1c > 8.0 in subjects with type 2 diabetes
* Moderate to severe heart failure (New York Heart Association class III or IV)
* Myocardial infarction or unstable angina pectoris within the past 12 months prior to IP initiation
* Uncontrolled hypertension as defined by a resting blood pressure * 150/90 mmHg prior to IP initiation (confirmed by a repeat assessment)
* Severe chronic pulmonary disease (eg, requiring oxygen therapy)
* Major chronic inflammatory disease or connective tissue disease (eg, rheumatoid arthritis, psoriasis, systemic lupus erythematosus)
* Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin).
Laboratory abnormalities
* Serum direct bilirubin * 1.5x ULN
* Hemoglobin < 10 g/dL
* Platelet count < 125,000 cells/mm3
* White blood cell count < 3,000 cells/mm3
* Absolute neutrophil count < 2000 cells/mm3
* Creatinine clearance < 50 mL/min (Cockroft-Gault formula, calculated value to be provided to sites).
4.2.19 Subject has used Tysabri (natalizumab) within 1 year prior to IP initiation.
4.2.21 Subject received an anti-TNF agent within 8 weeks prior to IP initiation.
4.2.22 Subject received steroid enemas 2 weeks prior to IP initiation.
4.2.23 Subject received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus within 4 weeks prior to IP initiation.
4.2.24 Chronic narcotic use for reasons other than diarrhea.
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 | EUCTR2010-019544-39-NL |
| ClinicalTrials.gov | NCT01150890 |
| CCMO | NL33509.029.10 |