Evaluation of Efficacy and Safety of Brazikumab (MEDI2070) in Participants With Active, Moderate to Severe Crohn's Disease

AstraZeneca

Status and phase: Terminated; Phase 2

Conditions: Crohn's Disease

Treatments: Drug: Placebo; Drug: Brazikumab IV Infusion; Drug: Brazikumab SC Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT02574637

2015-000609-38 (EudraCT Number)

D5170C00002

Details and patient eligibility

About

A Phase 2b study to evaluate the efficacy and safety of brazikumab (MEDI2070) in participants with moderate to severe Crohn's disease who have failed or are intolerant to anti-tumor necrosis factor-alpha (anti-TNFα) therapy.

Full description

This is a four-part Phase 2b study comprised of a 16-week, double-blind, placebo-controlled, Induction Period, a 12-week double-blind, placebo-controlled, Maintenance Period, a 24-week, Open-label Period and a post-treatment 28 week observational safety follow-up period designed to evaluate the short-term efficacy and the short- and long term safety of brazikumab in participants with moderate to severe, active Crohn's disease (CD) who have failed or are intolerant to anti-TNFα therapy as determined by the Investigator.

Enrollment: 29 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of ileal, ileo-colonic, or colonic Crohn's Disease (CD) for > 3 months prior to screening
• Men or women age 18 - 80 years at the time of screening
• Moderate to severely active CD, as defined by Crohn's Disease Activity Index (CDAI) and endoscopic demonstration of inflammation
• Stable dose of medications for Crohn's disease therapy
• Prior treatment failure or intolerance with at least one Anti-Tumor Necrosis Factor-Alpha Therapy (anti-TNF α) agent
• Effective contraception from screening, and for 36 weeks after the last dose of investigational product
• No known history of active tuberculosis (TB) & negative assessment for TB/latent TB

Exclusion criteria

• Severe underlying immunosuppression
• Severe gastrointestinal complications; e.g., short bowel syndromes, obstructing strictures, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation
• Significant infections at screening; Infected abscess, positive for Clostridium difficile, recent infectious hospitalization
• Recent treatment with approved or investigational biologic therapy for Crohn's disease
• Recent or planned live attenuated vaccine
• History of cancer, except for basal cell carcinoma or carcinoma in situ (CIS) of the cervix with apparent cure ≥ 12 months before screening
• Pregnancy/breast feeding
• Drug abuse

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

29 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo-matching brazikumab intravenous (IV) infusion and subcutaneous (SC) injection at Weeks 0 and 4 followed by placebo-matching brazikumab SC injection at Weeks 8 and 12 in the induction phase and at Weeks 16, 20 and 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection every 4 weeks up to Week 48 in the open-label period.

Treatment:

Drug: Brazikumab SC Injection

Drug: Brazikumab IV Infusion

Drug: Placebo

Brazikumab High Dose

Experimental group

Description:

Brazikumab 700 mg, IV infusion and placebo-matching brazikumab, SC injection at Weeks 0 and 4 followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.

Treatment:

Drug: Brazikumab SC Injection

Drug: Brazikumab IV Infusion

Drug: Placebo

Brazikumab High-Medium Dose

Experimental group

Description:

Brazikumab 280 mg, IV infusion and placebo-matching brazikumab, SC injection at Week 0 followed by brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.

Treatment:

Drug: Brazikumab SC Injection

Drug: Brazikumab IV Infusion

Drug: Placebo

Brazikumab Low-Medium Dose

Experimental group

Description:

Brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 105 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 105 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 105 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.

Treatment:

Drug: Brazikumab SC Injection

Drug: Brazikumab IV Infusion

Drug: Placebo

Brazikumab Low Dose

Experimental group

Description:

Brazikumab 70 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 35 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 35 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 35 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.

Treatment:

Drug: Brazikumab SC Injection

Drug: Brazikumab IV Infusion

Drug: Placebo