Crohn's Disease, IBD
Conditions
Keywords
Crohn's Disease, Inflammatory bowel disease, Brazikumab, IL23 receptor, IBD, CD
Brief summary
This study seeks to evaluate the safety and efficacy of brazikumab versus placebo (Stage I) and versus an active comparator (Stage 2) in participants with moderately to severely active CD and will include assessments of clinical response as demonstrated by improvement of symptoms and colonic mucosal appearance as observed on endoscopy
Interventions
DRUGBrazikumab low dose
Intravenous Brazikumab on Days 1, 29, and 57, followed by subcutaneous Brazikumab on Day 85 and every 4 weeks through Week 48
DRUGBrazikumab high dose
Intravenous Brazikumab on Days 1, 29, and 57, followed by subcutaneous Brazikumab on Day 85 and every 4 weeks through Week 48
DRUGHumira®
Administered subcutaneously on Day 1, Day 15, and Day 29 and every 2 weeks through Week 50.
DRUGPlacebo
Intravenous placebo on Days 1, 29, 57 followed by subcutaneous placebo on Day 85 and every 4 weeks through Week 48
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Inclusion and
Exclusion criteria
are the same for both Stage 1 and Stage 2; however, participants enrolled in Stage 1 will not be permitted to enroll in Stage 2. Inclusion Criteria: 1. At the time of signing the informed consent, the participant must be 18 to 80 years of age, inclusive. 2. A diagnosis of ileal, ileocolonic, or colonic CD with an onset of symptoms for a minimum of 3 months prior to Screening as determined by the investigator based on clinical history, exclusion of other etiologies including infectious causes, and characteristic endoscopic and/or histologic findings. 3. Moderately to severely active CD defined by a CDAI score of 220 to 450 AND; CDAI LSF score ≥ 5 OR CDAI AP score ≥ 2; AND SES-CD of at least 6 4. Participant had an inadequate response or intolerance to intervention with conventional treatment \[oral aminosalicylates, oral CS, azathioprine, methotrexate, or 6-mercaptopurine\], or prior biological treatment, or demonstrated CS dependence for the treatment of CD. For participants who have previously used biological treatment, a participant may have failed up to 3 biologics that include up to 2 different mechanisms of action. 5. Participants taking 5-aminosalicylates, Oral prednisone (or equivalent), Budesonide, Immunomodulators, Oral antibiotics, Immunomodulators, Probiotics must be at a stable dose. 6. Participant must have the QFT-TB test performed and meet the following TB criteria. A TB worksheet must also be completed: 1. Participant has no known history of active TB. 2. Participant has no known history of latent TB without completion of an appropriate course of intervention. 3. Meets 1 of the following acceptable TB test results: i. Negative QFT-TB obtained from central laboratory during Screening, OR ii. For a positive QFT-TB test obtained during Screening from the central laboratory, active TB must be ruled out or treated and negative QFT-TB confirmed by central laboratory OR iii. Indeterminate QFT-TB test obtained during the Screening Period from the central laboratory with ongoing QFT-TB testing as outlined in Appendix G. Participants with an indeterminate QFT-TB test can continue with Screening if they have all of the following: 1. no symptoms/risk factors per TB worksheet provided by the sponsor 2. no known recent exposure to a case of active TB 3. no evidence of active TB on chest x-ray within 8 weeks prior to Screening or during Screening 4. confirmed QFT-TB negative by central laboratory 7 Female participants of childbearing potential must have a negative urine pregnancy test prior to administration of study intervention and must agree to use a highly effective method of birth control (confirmed by the investigator) from randomization throughout the study duration and for at least 18 weeks after last dose of study intervention. 8 Women not of childbearing potential are defined as women who are either permanently sterilized or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomization without an alternative medical cause. 9 Nonsterilized males who are sexually active with a female partner of childbearing potential must comply with the methods of contraception during treatment and until the end of relevant systemic exposure in the male participant, plus a further 18 weeks. 10 Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol. 11 Willingness and ability to attend all study visits, comply with the study procedures, read and write in order to complete questionnaires, and be able to complete the study period. 12 Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative. Complete inclusion criteria are in the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1. Percentage of patients with CDAI remission | at Week 12 | CDAI remission is defined as achieving the CDAI score below 150 (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)). |
| Stage 2. Percentage of patients with endoscopic response | at Week 52 | Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score. |
| Stage 2. Percentage of patients with clinical remission | at Week 52 | Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: average daily LSF subscore of ≤ 3 as assessed on the CDAI LSF item AND average daily AP subscore of ≤ 1 as assessed on the CDAI AP item (measured by PRO questionnaire). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1. Percentage of patients with CDAI remission | at both Week 12 and Week 52 | CDAI remission is defined as achieving the CDAI score below 150 (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)). |
| Stage 1. Percentage of patients with endoscopic remission | at Week 52 | Endoscopic remission is defined as achieving the SES-CD total score of 0-2 OR SES-CD total score of ≤ 4 and at least 2 point reduction from Baseline with no subscore \> 1 |
| Stage 2. Exposure-response | Through Week 68 | Derive exposure response model linking primary endpoint to metrics of model predicted individual brazikumab exposures |
| Stage 2. Number and percentage of patients with adverse events | Through Week 68 | Number and percentage of patients with reported adverse events |
| Stage 1. Percentage of patients with SES-CD total score of 0-2 | at Week 52 | SES-CD total score of 0-2 |
| Stage 1. Percentage of patients with endoscopic response and endoscopic remission | Endoscopic response at Week 12, endoscopic remission at Week 52 | Endoscopic response: Minimum of 50% decrease from Baseline in SES-CD total score Endoscopic remission: SES-CD total score of 0-2, OR - SES-CD total score of ≤ 4 and at least 2 point reduction from Baseline with no subscore \> 1 |
| Stage 1. Serum concentration of brazikumab | Through Week 68 | Pharmacokinetics: concentration of brazikumab in serum |
| Stage 1. Incidence of anti-drug antibodies | Through Week 68 | Immunogenicity: incidence of brazikumab anti-drug antibodies in serum |
| Stage 1. Exposure-response | Through Week 68 | Derive exposure response model linking primary endpoint to metrics of model predicted individual brazikumab exposures |
| Stage 1. Serum IL-22 concentration clinical cutoff for Stage 2 | at Week 12 | Derive the relationship between baseline serum IL-22 concentration and efficacy of brazikumab through CDAI remission and endoscopic response |
| Stage 1. Number and percentage of patients with adverse events | Through Week 68 | Number and percentage of patients with reported adverse events. |
| Stage 1. Percentage of patients with potentially clinically significant changes in laboratory values | Through Week 68 | Percentage of patients with clinically significant changes in hematology, clinical chemistry, urinalysis. |
| Stage 1. Percentage of patients with potentially clinically significant changes in vital signs | Through Week 68 | Percentage of patients with potentially clinically significant changes in systolic, diastolic pulse rate. |
| Stage 1. Percentage of patients with potentially clinically significant changes in physical exams | Through Week 68 | Percentage of patients with potentially clinically significant changes in full physical exams. |
| Stage 1. Percentage of patients with endoscopic response | at Week 12 | Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score. |
| Stage 2. Percentage of patients with endoscopic response | at both Week 12 and Week 52 | Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score |
| Stage 2. Percentage of patients achieving CS-free endoscopic response | at Week 52 | Endoscopic response is described as minimum of 50% decrease from Baseline in SES-CD total score |
| Stage 2. Serum concentration of brazikumab | Through Week 68 | Pharmacokinetics: concentration of brazikumab in serum |
| Stage 2. Incidence of anti-drug antibodies | Through Week 68 | Immunogenicity: incidence of brazikumab anti-drug antibodies in blood serum |
| Stage 2. Percentage of patients with clinical remission | at both Week 12 and Week 52 | Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: average daily LSF subscore of ≤ 3 as assessed on the CDAI LSF item AND average daily AP subscore of ≤ 1 as assessed on the CDAI AP item (measured by PRO questrionare) |
| Stage 2: Percentage of patients with endoscopic remission | at Week 52 | Endoscopic remission: - SES-CD total score of 0-2, OR - SES-CD total score of ≤ 4 and at least 2 point reduction from Baseline with no subscore \> 1 |
| Stage 2: Percentage of patients with CS-free endoscopic remission | at Week 52 | Percentage of patients achieving Endoscopic remission and are CS-free where endoscopic remission is defined as : - SES-CD total score of 0-2, OR - SES-CD total score of ≤ 4 and at least 2 point reduction from Baseline with no subscore \> 1 |
| Stage 2. Percentage of patients with CS-free clinical remission | at Week 52 | Percentage of patients achieving CS-free average daily LSF subscore of ≤ 3 as assessed on the CDAI LSF item AND average daily AP subscore of ≤ 1 as assessed on the CDAI AP item |
| Stage 2: Percentage of patients with CS-free clinical remission | at Week 52 | For participants taking CS at Baseline, percentage of patients achieving CS-free clinical remission |
| Stage 2. Percentage of patients with endoscopic response and endoscopic remission | Endoscopic response at Week 12, endoscopic remission at Week 52 | Endoscopic response is defined as minimum of 50% decrease from Baseline in SES-CD total score Endoscopic remission: - SES-CD total score of 0-2, OR - SES-CD total score of ≤ 4 and at least 2 point reduction from Baseline with no subscore \> 1 |
| Stage 2. Percentage of patients with potentially clinically significant changes in laboratory values | Through Week 68 | Percentage of patients with clinically significant changes in hematology, clinical chemistry, urinalysis. |
| Stage 2. Percentage of patients with potentially clinically significant changes in vital signs | Through Week 68 | Percentage of patients with potentially clinically significant changes in systolic, diastolic pulse rate |
| Stage 2. Percentage of patients with potentially clinically significant changes in physical exams | Through Week 68 | Percentage of patients with potentially clinically significant changes in full physical exams |
| Stage 2. Percentage of patients with potentially clinically significant changes in ECGs | Through Week 68 | Percentage of patients with potentially clinically significant changes in 12-lead ECG recordings |
| Stage 1. Percentage of patients with potentially clinically significant changes in ECGs | Through Week 68 | Percentage of patients with potentially clinically significant changes in 12-lead ECG recordings |
| Stage 1. Percentage of patients with clinical remission | at Week 12 | Clinical remission is defined for a participant to satisfy the following two response thresholds simultaneously: average daily LSF subscore of ≤ 3 as assessed on the CDAI LSF item AND average daily AP subscore of ≤ 1 as assessed on the CDAI AP item (measured by PRO questionnaire). |
| Stage 1. Percentage of patients with CDAI response | at Week 12 | CDAI response is defined as achieving the CDAI score of \< 150 points or CDAI reduction from Baseline of ≥ 100 points (measured by PRO questionnaire and objective items (i.e. weight, hematocrit)). |
Countries
Canada, Czechia, Germany, Hungary, India, Israel, Italy, Poland, Russia, Slovakia, South Africa, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Outcome results
None listed