Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of GS-5745 (Andecaliximab) in Adults With Moderate to Severe Active Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Andecaliximab; Placebo to match Andecaliximab
Intervention description: Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection; Placebo to match andecaliximab administered by IV infusion
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Male or Female, 18 to 65 years of age

          -  Negative pregnancy test at screening

          -  Documented diagnosis of UC with a minimum disease extent of 15 centimeters (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 grams per deciliter (g/dL) (both males and females)

          -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1,500 milli meters [mm]^3)

          -  Platelets ≥ 100 x 10^9/L.

        Key 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-aminosalicylate (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.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.