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

Phase 1

Completed

• Conditions: Bacteremia
• Interventions: Drug: Placebo; Drug: DSTA4637S; Drug: SOC

• Registration Number: NCT03162250
• Lead Sponsor: Genentech, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-26
• Study First Submitted QC: 2017-05-19
• Study First Posted: 2017-05-22
• Study Start: 2017-07-13
• Status Verified: 2020-01
• Primary Completion: 2020-01-15
• Study Completion: 2020-01-15
• Last Update Submitted: 2020-01-21
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DSTA4637S low dose level + SOC	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.
DSTA4637S intermediate dose level+ SOC	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.
DSTA4637S high dose level+ SOC	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.
Placebo + SOC	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.
Placebo + SOC	Placebo	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.
DSTA4637S intermediate dose level+ SOC	DSTA4637S	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.
DSTA4637S high dose level+ SOC	DSTA4637S	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.
DSTA4637S low dose level + SOC	DSTA4637S	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events (AEs)	Baseline up to approximately 156 Days

Secondary Outcome Measures

Name	Time	Method
Measure of Unconjugated 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 Antibody-Conjugated 4-Dimethylamino Piperidino-Hydroxybenzoxazino Rifamycin (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

Trial Locations

Locations (16)

Asan Medical Center - Oncology; 🇰🇷 Seoul, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Seoul, Korea, Republic of

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Chungnam National University Hospital; 🇰🇷 Daejeon, Korea, Republic of

Gyeongsang National University Hospital; 🇰🇷 Gyeongsangnam-do, Korea, Republic of

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Los Angeles Biomedical Research Institute at Harbor-UCLA; 🇺🇸 Torrance, California, United States

William Beaumont Hospital; 🇺🇸 Royal Oak, Michigan, United States

Hospital Universitario de Bellvitge; 🇪🇸 Hospitalet de Llobregat, Barcelona, Spain

Hospital Mutua de Terrassa; 🇪🇸 Terrassa, Barcelona, Spain