E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011408 |
E.1.2 | Term | Crohns disease aggravated |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
• 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 |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Approximately 15 subjects per treatment arm (approximately 60 subjects total) will be enrolled in a PK substudy where the subjects will visit the clinic for additional pharmacokinetic sampling. Participation in the PK substudy is optional. In order to assure treatment balance in the PK substudy, randomization will be stratified by participation in the PK substudy. |
|
E.3 | Principal inclusion criteria |
Subject or subject’s legally acceptable representative has provided informed consent. Subject is ≥ 18 and ≤ 65 years of age at time of screening. Subject has diagnosed ileal, ileo-colonic, or colonic Crohn’s disease for a minimum of 6 months prior to initiating IP. Subject has moderately to severely active Crohn’s disease, as defined by a CDAI score ≥ 250 and ≤ 450 at baseline. 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). 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. Subject has a negative test at screening for hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus. Subject, if female and not at least 2 years postmenopausal or surgically sterile, has a negative serum pregnancy test within 4 weeks before initiating IP and a negative urine pregnancy test at baseline. 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. Subject meets regional recommendations for immunizations, eg, US Centers for Disease Control and Prevention (CDC) recommendations for subjects enrolled in the US. |
|
E.4 | Principal exclusion criteria |
Disease-specific criteria 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). Subject has had stricture with obstructive symptoms within 3 months prior to IP initiation. Subject underwent bowel surgery within 12 weeks prior to IP initiation. Subject has an ileostomy and/or colostomy. Subject has any gastric or intestinal pouch Subject has ulcerative colitis. Subject has evidence of an infected abscess. Subject has bowel perforation or evidence of noninflammatory obstruction during the 6 months prior to IP initiation. Subject has stool positive for C. Difficile toxin at screening. Other medical conditions Subject has any active CTCAE grade 2 or higher infection (including chronic or localized infections) within 6 weeks prior to IP initiation. Subject has a serious infection, defined as requiring hospitalization or intravenous antibiotics within 8 weeks prior to IP initiation. Subject has recurrent or chronic infections, defined as ≥ 3 infections requiring anti-microbials within the past 12 months prior to IP initiation. Subject has had a bone marrow transplant, stem cell transplant, or solid organ transplant 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). Subject has any condition that, in the opinion of the investigator, might cause this study to be detrimental to the subject. Laboratory abnormalities Subject has any of the following laboratory abnormalities at screening: • Elevated (> 2x ULN) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) • 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). Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results. Washouts and non-permitted drugs Subject currently is enrolled in another investigational device or drug study, or is less than 30 days since ending another investigational device or drug study(s), or is receiving other investigational agent(s), prior to IP initiation. Subject has used Tysabri (natalizumab) within 1 year prior to IP initiation. Subject received other commercially available or experimental biologic agents (eg, ustekinumab), experimental procedures, or live vaccines within 12 weeks prior to IP initiation. Subject received an anti-TNF agent within 8 weeks prior to IP initiation. Subject received steroid enemas 2 weeks prior to IP initiation. Subject received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide or tacrolimus within 4 weeks prior to IP initiation. Chronic narcotic use for reasons other than diarrhea. General or other Female subject is not willing to use highly effective contraception during treatment and for the duration of the study (except if at least 2 years postmenopausal or surgically sterile). Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the subject’s last study visit including the follow-up period. Subject has known or suspected sensitivity to mammalian cell-derived (ie, from Chinese hamster ovary) products or any components of the study drug. Subject will not be available for protocol required study visits, to the best of the subject and investigator’s knowledge. Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures. Subject previously has been randomized in this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is remission at week 6, as defined by a CDAI score of ≤ 150. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study is defined as the last study visit for the last subject. Enrollment is anticipated to take approximately 12 months. The anticipated total study duration from the first subject randomized to the last subject’s last visit is approximately 15 months |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |