Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of GS-5745 (Andecaliximab) in Adults With Moderate to Severe Active Ulcerative Colitis

NCT ID: NCT01831427

Last Updated: 2021-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-28
• Study Completion Date: 2015-02-06

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Andecaliximab 0.3 mg/kg IV single ascending dose (SAD)

Participants will receive andecaliximab 0.3 milligrams per kilogram (mg/kg) on Day 1.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Andecaliximab 1.0 mg/kg IV (SAD)

Participants will receive andecaliximab 1.0 mg/kg on Day 1.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Andecaliximab 2.5 mg/kg IV (SAD)

Participants will receive andecaliximab 2.5 mg/kg on Day 1.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Andecaliximab 5.0 mg/kg IV (SAD)

Participants will receive andecaliximab 5.0 mg/kg on Day 1.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Placebo Pooled (SAD)

Participants will receive placebo on Day 1.

Group Type: PLACEBO_COMPARATOR

Placebo to match Andecaliximab

Intervention Type: DRUG

Placebo to match andecaliximab administered by IV infusion

Andecaliximab 0.3 mg/kg IV multiple ascending doses (MAD)

Participants will receive andecaliximab 0.3 mg/kg on Days 1, 15, and 29.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Andecaliximab 1.0 mg/kg IV (MAD)

Participants will receive andecaliximab 1.0 mg/kg on Days 1, 15, and 29.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Andecaliximab 2.5 mg/kg IV (MAD)

Participants will receive andecaliximab 2.5 mg/kg on Days 1, 15, and 29.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Andecaliximab 5.0 mg/kg IV (MAD)

Participants will receive andecaliximab 5.0 mg/kg on Days 1, 15, and 29.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Andecaliximab 150 mg SC (Adaptive MAD)

Participants will receive andecaliximab 150 mg on Days 1, 8, 15, 22, and 29.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Placebo Pooled (MAD)

Participants will receive placebo on Days 1, 15, and 29.

Group Type: PLACEBO_COMPARATOR

Placebo to match Andecaliximab

Intervention Type: DRUG

Placebo to match andecaliximab administered by IV infusion

Interventions

Andecaliximab

Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection

Intervention Type: DRUG

Placebo to match Andecaliximab

Placebo to match andecaliximab administered by IV infusion

Intervention Type: DRUG

Other Intervention Names

GS-5745

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Delta Research Partners LLC

Monroe, Louisiana, United States

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Clinical Research Institute of Michigan

Chesterfield Township, MI 48047, Michigan, United States

Ehrhardt Clinical Research, LLC

Belton, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

Community Research

Cincinnati, Ohio, United States

UZ Leuven

Leuven, , Belgium

GIRI

Vancouver, British Columbia, Canada

LHSC University Campus

London, Ontario, Canada

Clinical Pharma Center of Kenezy Gyula Korhaz Rendelointezet

Debrecen, Hajdú-Bihar, Hungary

Semmelweis Egyetem Altalanos Orvostudomanyi Kar

Budapest, Pest County, Hungary

Drug Research Centre

Balatonfüred, , Hungary

Republican Clinical Hospital

Chisinau, , Moldova

Academic Medical Center

Amsterdam, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Institute of Pulmonology "Marius Nasta"

Bucharest, , Romania

Countries

United States; Belgium; Canada; Hungary; Moldova; Netherlands; Romania

References

Bhandari BR, Fogel R, Onken J, Yen EH, Kanwar B, Subramanian GM, McHutchison GJ, et al. Safety and Efficacy of GS-5745 an Anti-Matrix Metalloproteinase 9 (MMP) Monoclonal Antibody in Patients with Moderately to Severely Active Ulcerative Colitis. Gastroenterology 2015;148 (4): S-1196.

Reference Type: RESULT

Other Identifiers

2013-000305-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-326-0101

Identifier Type: -

Identifier Source: org_study_id