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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03162250
• Collaborator: (none)
• Enrollment: 27
• Locations: 16
• Arms: 4
• Actual Duration (Months): 30.1
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bacteremia	Drug: DSTA4637S; Drug: Placebo; Drug: SOC	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 13, 2017
• Actual Primary Completion Date: Jan 15, 2020
• Actual Study Completion Date: Jan 15, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) [Baseline up to approximately 156 Days]

Secondary Outcome Measures

1. Measure of Antibody-Conjugated 4-Dimethylamino Piperidino-Hydroxybenzoxazino Rifamycin (dmDNA31) measured by Plasma [Baseline up to approximately 156 Days]

2. Measure of DSTA4637S Total Antibody measured by Serum [Baseline up to approximately 156 Days]

3. Measure of Unconjugated dmDNA31 measured by Plasma [Baseline up to approximately 156 Days]

4. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to DSTA4637S [Baseline up to approximately 156 Days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles Biomedical Research Institute at Harbor-UCLA	Torrance	California	United States	90502
2	Henry Ford Health System	Detroit	Michigan	United States	48202
3	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
4	Duke University Medical Center	Durham	North Carolina	United States	27705
5	Chungnam National University Hospital	Daejeon		Korea, Republic of	35015
6	Gyeongsang National University Hospital	Gyeongsangnam-do		Korea, Republic of	52727
7	Asan Medical Center - Oncology	Seoul		Korea, Republic of	05505
8	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
9	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
10	Hospital Mutua de Terrassa	Terrassa	Barcelona	Spain	08221
11	Hospital Universitario Marques de Valdecilla	Santander	Cantabria	Spain	39008
12	Hospital del Mar	Barcelona		Spain	08003
13	Hospital Clinic de Barcelona	Barcelona		Spain	08036
14	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
15	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
16	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013

Sponsors and Collaborators

• Genentech, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03162250
• Other Study ID Numbers: GV39131; 2016-001880-35
• First Posted: May 22, 2017
• Last Update Posted: Jan 22, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Bacteremia

Study Results

No Results Posted as of Jan 22, 2020