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

NCT03162250 | Completed Phase 1 FDA Drug

• 2 other identifiers: GV391312016-001880-35
• Study Type: interventional
• Target: 27
• Locations: 3 countries
• Sites: 16

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.

Conditions

Bacteremia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Adverse Events (AEs)

  Baseline up to approximately 156 Days

Secondary Outcomes (4)

• 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

Study Arms (4)

DSTA4637S low dose level + SOC

EXPERIMENTAL

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; Drug: SOC

DSTA4637S intermediate dose level+ SOC

EXPERIMENTAL

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; Drug: SOC

DSTA4637S high dose level+ SOC

EXPERIMENTAL

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; Drug: SOC

Placebo + SOC

PLACEBO COMPARATOR

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: Placebo; Drug: SOC

Interventions

DSTA4637S DRUG

DSTA4637S will be administered as an IV infusion at 3 dose levels.

DSTA4637S high dose level+ SOC; DSTA4637S intermediate dose level+ SOC; DSTA4637S low dose level + SOC

Placebo DRUG

Placebo matched to DSTA4637S IV infusion will be administered as specified.

Placebo + SOC

SOC DRUG

Anti-staphylococcal SOC antibiotics dosage and duration of therapy will be based on relevant health-authority approved indications and local and national treatment guidelines.

DSTA4637S high dose level+ SOC; DSTA4637S intermediate dose level+ SOC; DSTA4637S low dose level + SOC; Placebo + SOC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (16)

Los Angeles Biomedical Research Institute at Harbor-UCLA

Torrance, California, 90502, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Gyeongsang National University Hospital

Gyeongsangnam-do, 52727, South Korea

Location

Asan Medical Center - Oncology

Seoul, 05505, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Bacteremia

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 22, 2017
• Study Start: July 13, 2017
• Primary Completion: January 15, 2020
• Study Completion: January 15, 2020
• Last Updated: January 22, 2020

Record last verified: 2020-01

Locations

ES (8); US (4); KR (4)