Overview

This trial is active, not recruiting.

Condition ulcerative colitis
Treatments gs-5745, placebo to match gs-5745
Phase phase 1
Target MMP-9
Sponsor Gilead Sciences
Start date March 2013
End date January 2015
Trial size 74 participants
Trial identifier NCT01831427, GS-US-326-0101

Summary

This is a staggered, placebo-controlled, single and multiple ascending dose (SAD/MAD) study evaluating the safety, tolerability and pharmacokinetics of GS-5745 in participants with moderately to severely active ulcerative colitis. This study will provide valuable data that can help establish the safety, pharmacokinetics and efficacy of GS-5745 in participants with ulcerative colitis.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Experimental)
(IV dose at 0.3 mg/kg, 1.0 mg/kg, 2.5 mg/kg, or 5.0 mg/kg and subcutaneous dose at 150 mg) Participants will receive GS-5745 as follows: SAD cohort - single IV dose; MAD cohort - multiple (three) IV doses every two weeks; Adaptive MAD cohort - a single subcutaneous dose for 5 consecutive weeks
gs-5745
GS-5745 administered by intravenous infusion or subcutaneous injection
(Experimental)
Participants will receive placebo to match GS-5745 as follows: SAD cohort - single IV dose; MAD cohort - multiple (three) IV doses every two weeks; Participants will receive GS-5745 150 mg as follows: Adaptive MAD cohort - a single subcutaneous dose for 5 consecutive weeks
gs-5745
GS-5745 administered by intravenous infusion or subcutaneous injection
placebo to match gs-5745
Placebo to match GS-5745 administered by intravenous infusion

Primary Outcomes

Measure
Evaluating the safety and tolerability throughout the duration of the study
time frame: SAD Cohort: through Day 41, MAD/Adaptive MAD Cohort: through Day 71
Pharmacokinetics (PK) of GS-5745 following SAD and MAD/adaptive MAD doses of GS-5745
time frame: SAD Cohort: through Day 43; MAD/Adaptive MAD Cohort: through Day 71

Secondary Outcomes

Measure
Pharmacokinetics (PK) of GS-5745 following SAD and MAD/adaptive MAD doses of GS-5745
time frame: SAD Cohort: through Day 43; MAD/Adpative MAD Cohort: through Day 71

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Male or Female, 18 to 65 years of age - Negative pregnancy test at screening - Documented diagnosis of ulcerative colitis (UC) with a minimum disease extent of 15 cm from the anal verge - Mayo Score of at least 3 for the SAD cohort and Mayo Score of at least 6 for the MAD cohorts - Hepatic panel (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, direct bilirubin, alkaline phosphatase, lactate dehydrogenase [LDH] ≤ 2 times the upper limit of the normal range [ULN]) - Serum creatinine ≤ 1.5 times the ULN - Hemoglobin ≥ 10 g/dL (both males and females) - Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1,500 mm^3) - Platelets ≥ 100 x 10^9/L Exclusion Criteria: - Pregnant or lactating females - Exhibit severe UC/ clinically significant active infection - Current use of oral corticosteroids at a dose equivalent to > 20 mg/day of prednisone - Any dose adjustment in oral corticosteroids or oral immunosuppressants (6-MP, Azathioprine), or oral 5-ASA compounds within 30 days of Baseline - Use of rectal formulations of 5-ASA compounds or corticosteroids within 2 weeks prior to randomization - Crohn's disease or indeterminate colitis - History of colectomy, partial colectomy, or dysplasia on biopsy - Stool sample positive for Clostridium difficile (C. difficile) toxin, E. coli, Salmonella, Shigella, Campylobacter or Yersinia - Treatment with Infliximab, Adalimumab, Natalizumab, Golimumab, Vedolizumab or Certolizumab within 8 weeks of randomization - Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) that, in the opinion of the Investigator, would make the individual unsuitable for the study or would prevent compliance with the study protocol

Additional Information

Official title A Phase 1 Double-blind, Randomized, Placebo-Controlled, Staggered, Single and Multiple Ascending Dose, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of GS-5745 in Subjects With Moderate to Severe Ulcerative Colitis
Description The study will test the safety of the drug and a system has been built into the trial design to ensure participant safety. Participants will be given different concentrations of the drug (known as "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 GS-5745 150 mg prefilled syringe once a week for 5 weeks.
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by Gilead Sciences.