Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Participants With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care (SOC) Antibiotics

A Phase IB, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Patients With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care Antibiotics

This is a Phase Ib, randomized double-blind, placebo-controlled multiple-ascending dose study to investigate the safety, tolerability, and pharmacokinetics of multiple doses of DSTA4637S when given in addition to anti-staphylococcal SOC antibiotics to participants with methicillin-resistant staphylococcus aureus (MRSA) and methicillin-sensitive staphylococcus aureus (MSSA) bacteremia requiring at least 4 weeks of anti-staphylococcal SOC antibiotics.

Study Overview

• Status: Completed
• Conditions: Bacteremia
• Intervention / Treatment: Drug: DSTA4637S; Drug: SOC; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Gyeongsangnam-do, Korea, Republic of, 52727
    • Gyeongsang National University Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - Oncology
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
    • Terrassa, Barcelona, Spain, 08221
      • Hospital Mutua De Terrassa
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
• United States
  • California
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute at Harbor-UCLA
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index greater than or equal (>/=) 18 to less than or equal to (</=) 40 kg/m^2
• At randomization, participants must have >/=1 blood culture or molecular diagnostic that is positive for Staphylococcal aureus (S. aureus) collected in the previous 120 hours
• In the investigator's judgment, an expected treatment duration for S. aureus intravenous infection with anti-staphylococcal SOC antibiotics >/= 4 weeks

Exclusion Criteria:

• The presence of an intravascular catheter that is not planned to be removed within 96 hours of study randomization
• S. aureus bacteremia associated with an intracardiac device and/or intravascular prosthetic material (including hemodialysis access graft)
• In the investigator's judgement, S. aureus bacteremia involving infection of a prosthetic joint or vertebral hardware
• In participants with cirrhosis, a Child-Pugh Score of Class B or C
• Known rifampicin-resistant S. aureus
• Anticipated receipt of a rifamycin class (excluding rifaxamin) antibiotic from Day 1 to study completion/discontinuation
• In the investigator's judgment, the need for emergent valve surgery at the time of randomization or a high likelihood of cardiac surgery within 3 days after randomization
• Polymicrobial bacteremia
• Participants with significant immune suppression
• Participants with evidence of liver disease
• History or presence of an abnormal electrocardiogram (ECG)
• Exposure to any biological therapy or investigational biological agent within 90 days prior to the screening evaluation or have received any other investigational treatment 30 days prior to the screening evaluation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DSTA4637S low dose level + SOC; DSTA4637S low dose level intravenous (IV) infusion will be administered within 24 hours of randomization on Day 1 and then every 7 days up to 6 doses of study drug in addition to anti-staphylococcal SOC antibiotics.	Drug: DSTA4637S; DSTA4637S will be administered as an IV infusion at 3 dose levels.; Drug: SOC; Anti-staphylococcal SOC antibiotics dosage and duration of therapy will be based on relevant health-authority approved indications and local and national treatment guidelines.
EXPERIMENTAL: DSTA4637S intermediate dose level+ SOC; DSTA4637S intermediate dose level IV infusion will be administered within 24 hours of randomization on Day 1 and then every 7 days up to 6 doses of study drug in addition to anti-staphylococcal SOC antibiotics.	Drug: DSTA4637S; DSTA4637S will be administered as an IV infusion at 3 dose levels.; Drug: SOC; Anti-staphylococcal SOC antibiotics dosage and duration of therapy will be based on relevant health-authority approved indications and local and national treatment guidelines.
EXPERIMENTAL: DSTA4637S high dose level+ SOC; DSTA4637S high dose level IV infusion will be administered within 24 hours of randomization on Day 1 and then every 7 days up to 6 doses of study drug in addition to anti-staphylococcal SOC antibiotics.	Drug: DSTA4637S; DSTA4637S will be administered as an IV infusion at 3 dose levels.; Drug: SOC; Anti-staphylococcal SOC antibiotics dosage and duration of therapy will be based on relevant health-authority approved indications and local and national treatment guidelines.
PLACEBO_COMPARATOR: Placebo + SOC; Placebo matched to DSTA4637S IV infusion will be administered within 24 hours of randomization on Day 1 and then every 7 days up to 6 doses of study drug in addition to anti-staphylococcal SOC antibiotics.	Drug: SOC; Anti-staphylococcal SOC antibiotics dosage and duration of therapy will be based on relevant health-authority approved indications and local and national treatment guidelines.; Drug: Placebo; Placebo matched to DSTA4637S IV infusion will be administered as specified.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Adverse Events (AEs)	Baseline up to approximately 156 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Measure of Antibody-Conjugated 4-Dimethylamino Piperidino-Hydroxybenzoxazino Rifamycin (dmDNA31) measured by Plasma	Baseline up to approximately 156 Days
Measure of DSTA4637S Total Antibody measured by Serum	Baseline up to approximately 156 Days
Measure of Unconjugated dmDNA31 measured by Plasma	Baseline up to approximately 156 Days
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to DSTA4637S	Baseline up to approximately 156 Days

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 13, 2017
• Primary Completion (ACTUAL): January 15, 2020
• Study Completion (ACTUAL): January 15, 2020

Study Registration Dates

• First Submitted: April 26, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (ACTUAL): May 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Bacteremia
• Other Study ID Numbers: GV39131; 2016-001880-35 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No