Clinical trial NCT01831427
Conditions: Ulcerative Colitis
Sponsor: Gilead Sciences
Start date: 2013-03-28; Completion date: 2015-02-06
Enrollment: 74 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The primary objectives of this study are as follows:

* To assess the safety and tolerability of escalating single and multiple doses of GS-5745 (andecaliximab) in participants with moderate to severe ulcerative colitis (UC) as assessed by adverse events (AEs) and laboratory abnormalities
* To assess the pharmacokinetics (PK) of GS-5745 (andecaliximab) in participants with moderate to severe UC.

Detailed description:
The study will test the safety of the drug. Participants will be given different concentrations of the drug in Cohorts, starting from a lower dose to a higher dose.

Single-Dose Treatment:

A thorough assessment of safety and tolerability will be performed before escalating to the next higher dose. For example, the first 2 participants will be dosed in a staggered fashion 24 hours apart. Provided that there are no significant safety signals up to 24 hours post-dose for the first 2 participants, the remaining 4 participants will be dosed. A thorough assessment of safety and tolerability (through Day 14 post-dose) will be performed by the safety review committee before escalating to the next higher dose. Participants enrolled in a SAD cohort will be eligible to participate in a MAD or adaptive MAD cohort if eligibility criteria are met.

Multiple-Dose Treatment:

This design follows the same set-up as the Single-Dose Treatment. Dosing will not commence in the first MAD cohort until safety data from the second dose level SAD cohort has been reviewed through Day 15. Successive MAD cohorts will only be dosed after safety data from the previous, lower dose MAD cohort through Day 43 and the next higher dose SAD cohort through Day 15, have been reviewed by the safety review committee. An additional Adaptive MAD cohort will explore a subcutaneous dosing of andecaliximab 150 mg prefilled syringe once a week for 5 weeks.

Arms: arm 1: Participants will receive andecaliximab 0.3 milligrams per kilogram (mg/kg) on Day 1. arm 2: Participants will receive andecaliximab 1.0 mg/kg on Day 1. arm 3: Participants will receive andecaliximab 2.5 mg/kg on Day 1. arm 4: Participants will receive andecaliximab 5.0 mg/kg on Day 1. arm 5: Participants will receive placebo on Day 1. arm 6: Participants will receive andecaliximab 0.3 mg/kg on Days 1, 15, and 29. arm 7: Participants will receive andecaliximab 1.0 mg/kg on Days 1, 15, and 29. arm 8: Participants will receive andecaliximab 2.5 mg/kg on Days 1, 15, and 29. arm 9: Participants will receive andecaliximab 5.0 mg/kg on Days 1, 15, and 29. arm 10: Participants will receive andecaliximab 150 mg on Days 1, 8, 15, 22, and 29. arm 11: Participants will receive placebo on Days 1, 15, and 29.
Interventions: intervention 1: Andecaliximab intervention 2: Placebo to match Andecaliximab
Intervention descriptions: intervention 1: Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection intervention 2: Placebo to match andecaliximab administered by IV infusion

Protocol documents: