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

NCT01831427 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: GS-US-326-01012013-000305-23
• Study Type: interventional
• Target: 74
• Locations: 7 countries
• Sites: 16

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.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (7)

• Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD)

  TEAEs are any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.

  SAD Cohorts: First dose date (Day 1) plus 30 days, MAD/Adaptive MAD Cohort: First dose date up to last dose date (Maximum: Day 29) plus 30 days

• Pharmacokinetic (PK) Parameter: Cmax (SAD)

  Cmax is defined as the maximum concentration of drug.

  Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43

• PK Parameter: Cmax (MAD)

  Cmax is defined as the maximum concentration of drug over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36.

  MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29, Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29, Predose on Days 8 and 36

• PK Parameter: Ctau (MAD)

  Ctau is defined as the observed drug concentration at the end of the dosing interval.

  MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Day 29; Predose on Day 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Day 29; Predose on Day 36

• PK Parameter: AUCinf (SAD)

  AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.

  Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43

• PK Parameter: AUCtau (MAD)

  AUCtau is defined as the area under the plasma concentration versus time curve over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36.

  MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29; Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29; Predose on Days 8 and 36

• PK Parameter: AUClast (SAD)

  AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last observable concentration.

  Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43

Study Arms (11)

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

EXPERIMENTAL

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

Drug: Andecaliximab

Andecaliximab 1.0 mg/kg IV (SAD)

EXPERIMENTAL

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

Drug: Andecaliximab

Andecaliximab 2.5 mg/kg IV (SAD)

EXPERIMENTAL

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

Drug: Andecaliximab

Andecaliximab 5.0 mg/kg IV (SAD)

EXPERIMENTAL

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

Drug: Andecaliximab

Placebo Pooled (SAD)

PLACEBO COMPARATOR

Participants will receive placebo on Day 1.

Drug: Placebo to match Andecaliximab

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

EXPERIMENTAL

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

Drug: Andecaliximab

Andecaliximab 1.0 mg/kg IV (MAD)

EXPERIMENTAL

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

Drug: Andecaliximab

Andecaliximab 2.5 mg/kg IV (MAD)

EXPERIMENTAL

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

Drug: Andecaliximab

Andecaliximab 5.0 mg/kg IV (MAD)

EXPERIMENTAL

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

Drug: Andecaliximab

Andecaliximab 150 mg SC (Adaptive MAD)

EXPERIMENTAL

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

Drug: Andecaliximab

Placebo Pooled (MAD)

PLACEBO COMPARATOR

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

Drug: Placebo to match Andecaliximab

Interventions

Andecaliximab DRUG

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

Also known as: GS-5745

Andecaliximab 0.3 mg/kg IV multiple ascending doses (MAD); Andecaliximab 0.3 mg/kg IV single ascending dose (SAD); Andecaliximab 1.0 mg/kg IV (MAD); Andecaliximab 1.0 mg/kg IV (SAD); Andecaliximab 150 mg SC (Adaptive MAD); Andecaliximab 2.5 mg/kg IV (MAD); Andecaliximab 2.5 mg/kg IV (SAD); Andecaliximab 5.0 mg/kg IV (MAD); Andecaliximab 5.0 mg/kg IV (SAD)

Placebo to match Andecaliximab DRUG

Placebo to match andecaliximab administered by IV infusion

Placebo Pooled (MAD); Placebo Pooled (SAD)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (16)

Delta Research Partners LLC

Monroe, Louisiana, 71201, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States

Location

Clinical Research Institute of Michigan

Chesterfield Township, MI 48047, Michigan, 48047, United States

Location

Ehrhardt Clinical Research, LLC

Belton, Missouri, 64012, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Community Research

Cincinnati, Ohio, 45255, United States

Location

UZ Leuven

Leuven, 3000, Belgium

Location

GIRI

Vancouver, British Columbia, V6Z 2K5, Canada

Location

LHSC University Campus

London, Ontario, N6A 5A5, Canada

Location

Clinical Pharma Center of Kenezy Gyula Korhaz Rendelointezet

Debrecen, Hajdú-Bihar, 4031, Hungary

Location

Semmelweis Egyetem Altalanos Orvostudomanyi Kar

Budapest, Pest County, 1083, Hungary

Location

Drug Research Centre

Balatonfüred, 8230, Hungary

Location

Republican Clinical Hospital

Chisinau, 2025, Moldova

Location

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6229 HX, Netherlands

Location

Institute of Pulmonology "Marius Nasta"

Bucharest, 050159, Romania

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

andecaliximab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2013
• First Posted: April 15, 2013
• Study Start: March 28, 2013
• Primary Completion: January 5, 2015
• Study Completion: February 6, 2015
• Last Updated: February 1, 2021
• Results First Posted: February 1, 2021

Record last verified: 2021-01

Locations

US (6); MO (1); NL (2); HU (3); BE (1); RO (1); CA (2)