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

Primary Purpose

Ulcerative Colitis

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Andecaliximab
Placebo to match Andecaliximab
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Delta Research Partners LLC
  • Walter Reed National Military Medical Center
  • Clinical Research Institute of Michigan
  • Ehrhardt Clinical Research, LLC
  • Duke University Medical Center
  • Community Research
  • UZ Leuven
  • GIRI
  • LHSC University Campus
  • Clinical Pharma Center of Kenezy Gyula Korhaz Rendelointezet
  • Semmelweis Egyetem Altalanos Orvostudomanyi Kar
  • Drug Research Centre
  • Republican Clinical Hospital
  • Academic Medical Center
  • Academisch Ziekenhuis Maastricht
  • Institute of Pulmonology "Marius Nasta"

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

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

Andecaliximab 1.0 mg/kg IV (SAD)

Andecaliximab 2.5 mg/kg IV (SAD)

Andecaliximab 5.0 mg/kg IV (SAD)

Placebo Pooled (SAD)

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

Andecaliximab 1.0 mg/kg IV (MAD)

Andecaliximab 2.5 mg/kg IV (MAD)

Andecaliximab 5.0 mg/kg IV (MAD)

Andecaliximab 150 mg SC (Adaptive MAD)

Placebo Pooled (MAD)

Arm Description

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

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

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

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

Participants will receive placebo on Day 1.

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.
Pharmacokinetic (PK) Parameter: Cmax (SAD)
Cmax is defined as the maximum concentration of drug.
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.
PK Parameter: Ctau (MAD)
Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: AUCinf (SAD)
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
April 8, 2013
Last Updated
January 5, 2021
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01831427
Brief Title
Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of GS-5745 (Andecaliximab) in Adults With Moderate to Severe Active Ulcerative Colitis
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
March 28, 2013 (Actual)
Primary Completion Date
January 5, 2015 (Actual)
Study Completion Date
February 6, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Andecaliximab 0.3 mg/kg IV single ascending dose (SAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 0.3 milligrams per kilogram (mg/kg) on Day 1.
Arm Title
Andecaliximab 1.0 mg/kg IV (SAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 1.0 mg/kg on Day 1.
Arm Title
Andecaliximab 2.5 mg/kg IV (SAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 2.5 mg/kg on Day 1.
Arm Title
Andecaliximab 5.0 mg/kg IV (SAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 5.0 mg/kg on Day 1.
Arm Title
Placebo Pooled (SAD)
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo on Day 1.
Arm Title
Andecaliximab 0.3 mg/kg IV multiple ascending doses (MAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 0.3 mg/kg on Days 1, 15, and 29.
Arm Title
Andecaliximab 1.0 mg/kg IV (MAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 1.0 mg/kg on Days 1, 15, and 29.
Arm Title
Andecaliximab 2.5 mg/kg IV (MAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 2.5 mg/kg on Days 1, 15, and 29.
Arm Title
Andecaliximab 5.0 mg/kg IV (MAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 5.0 mg/kg on Days 1, 15, and 29.
Arm Title
Andecaliximab 150 mg SC (Adaptive MAD)
Arm Type
Experimental
Arm Description
Participants will receive andecaliximab 150 mg on Days 1, 8, 15, 22, and 29.
Arm Title
Placebo Pooled (MAD)
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo on Days 1, 15, and 29.
Intervention Type
Drug
Intervention Name(s)
Andecaliximab
Other Intervention Name(s)
GS-5745
Intervention Description
Andecaliximab administered by intravenous (IV) infusion or subcutaneous (SC) injection
Intervention Type
Drug
Intervention Name(s)
Placebo to match Andecaliximab
Intervention Description
Placebo to match andecaliximab administered by IV infusion
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD)
Description
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.
Time Frame
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
Title
Pharmacokinetic (PK) Parameter: Cmax (SAD)
Description
Cmax is defined as the maximum concentration of drug.
Time Frame
Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43
Title
PK Parameter: Cmax (MAD)
Description
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.
Time Frame
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
Title
PK Parameter: Ctau (MAD)
Description
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time Frame
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
Title
PK Parameter: AUCinf (SAD)
Description
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.
Time Frame
Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43
Title
PK Parameter: AUCtau (MAD)
Description
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.
Time Frame
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
Title
PK Parameter: AUClast (SAD)
Description
AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last observable concentration.
Time Frame
Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Delta Research Partners LLC
City
Monroe
State/Province
Louisiana
ZIP/Postal Code
71201
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889-5600
Country
United States
Facility Name
Clinical Research Institute of Michigan
City
Chesterfield Township, MI 48047
State/Province
Michigan
ZIP/Postal Code
48047
Country
United States
Facility Name
Ehrhardt Clinical Research, LLC
City
Belton
State/Province
Missouri
ZIP/Postal Code
64012
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Community Research
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45255
Country
United States
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
GIRI
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
Facility Name
LHSC University Campus
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Clinical Pharma Center of Kenezy Gyula Korhaz Rendelointezet
City
Debrecen
State/Province
Hajdú-Bihar
ZIP/Postal Code
4031
Country
Hungary
Facility Name
Semmelweis Egyetem Altalanos Orvostudomanyi Kar
City
Budapest
State/Province
Pest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Drug Research Centre
City
Balatonfured
ZIP/Postal Code
8230
Country
Hungary
Facility Name
Republican Clinical Hospital
City
Chisinau
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Academic Medical Center
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Academisch Ziekenhuis Maastricht
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
Facility Name
Institute of Pulmonology "Marius Nasta"
City
Bucharest
ZIP/Postal Code
050159
Country
Romania

12. IPD Sharing Statement

Citations:
Citation
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.
Results Reference
result

Learn more about this trial

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

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