Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection (SOLO II)

A Multicenter, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Single-Dose IV Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection (SOLO II)

The purpose of this Phase 3 trial is to evaluate the efficacy, safety, and tolerability of oritavancin in ABSSSIs, including those caused by MRSA and to evaluate the potential economic benefit of oritavancin administered as a single 1200 mg IV dose.

Study Overview

• Status: Completed
• Conditions: Abscess; Cellulitis; Wound Infection; Systemic Inflammation
• Intervention / Treatment: Drug: Single-Dose IV Oritavancin Diphosphate; Drug: IV Vancomycin

Detailed Description

This is a Phase 3, multicenter, randomized, double-blind, parallel, comparative efficacy and safety study of single-dose IV oritavancin/IV placebo versus IV vancomycin for 7 to 10 days in adults with acute bacterial skin and skin structure infection (ABSSSI) suspected or proven to be caused by Gram-positive pathogens. Approximately 960 patients will be randomized at 100 centers globally.

In addition, this study will characterize the PK and PK/PD properties of a single 1200 mg IV dose of oritavancin and evaluate the potential health economic benefits offered by this dosing strategy.

• Study Type: Interventional
• Enrollment (Actual): 1019
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91942
      • Sharp Grossmont Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects may be included in the study if they meet all of the following inclusion criteria:

1. Males or females ≥18 years old
2. Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 5 days of IV therapy
3. An ABSSSI includes one of the following infections Wound infections, Cellulitis/erysipelas, Major cutaneous abscess
4. ABSSSI must present with at least 2 signs and symptoms
5. Able to give informed consent and willing to comply with all required study procedures

Exclusion Criteria:

Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

1. Prior systemic or topical antibacterial therapy with activity against suspected or proven Gram-positive pathogens within the preceding 14 days

   • The causative Gram-positive pathogen(s) isolated from the ABSSSI site is resistant in vitro to the antibacterial(s) that was administered with documented clinical progression, or
   • Documented failure to previous ABSSSI antibiotic therapy is available. Documentation of treatment failure must be recorded
   • Patient received a single dose of a short acting antibacterial therapy three or more days before randomization
2. Infections associated with, or in close proximity to, a prosthetic device
3. Severe sepsis or refractory shock
4. Known or suspected bacteremia at time of screening

5. ABSSSI due to or associated with any of the following:

   • Infections suspected or documented to be caused by Gram-negative pathogens -- Wound infections (surgical or traumatic) and abscesses with only Gram-negative pathogens
   • Diabetic foot infections
   • Concomitant infection at another site not including a secondary ABSSSI lesion
   • Infected burns
   • A primary infection secondary to a pre-existing skin disease with associated inflammatory changes
   • Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease
   • Any evolving necrotizing process gangrene or infection suspected or proven to be caused by Clostridium species
   • Infections known to be caused by a Gram-positive organism with a vancomycin MIC >2 μg/mL or clinically failing prior therapy with glycopeptides
   • Catheter site infections
6. Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria
7. Currently receiving chronic systemic immunosuppressive therapy
8. AIDS with CD4 count < 200 cells/mm3
9. Neutropenia
10. Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI
11. Women who are pregnant or nursing
12. History of immune-related hypersensitivity reaction to glycopeptides
13. Patients that require anticoagulant monitoring with an aPTT
14. Contraindication to vancomycin
15. Patients unwilling to forego blood and/or blood product donation
16. Treatment with investigational medicinal product within 30 days before enrollment and for the duration of the study
17. Investigational device present, or removed <30 days before enrollment, or presence of device-related infection
18. Patients unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study
19. Severe hepatic disease
20. Presence of hyperuricemia
21. Unwilling to refrain from chronic use of any medication with antipyretic properties

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-Dose IV Oritavancin Diphosphate	Drug: Single-Dose IV Oritavancin Diphosphate; Intravenous oritavancin and IV placebo or IV vancomycin will be administered for a minimum of 7 days up to a maximum of 10 days.
Active Comparator: IV Vancomycin	Drug: IV Vancomycin; Intravenous oritavancin and IV placebo or IV vancomycin will be administered for a minimum of 7 days up to a maximum of 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Clinical Response	Clinical response at the ECE visit (48-72 hours following initiation of study drug administration). Early clinical response was defined as a composite outcome based on, cessation of spreading or reduction in the size of baseline lesion, absence of fever and no rescue antibiotic medication.	48-72 hours after the initation of study therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint)	Compared the clinical efficacy at the Post Therapy Evaluation of Oritavancin and Vancomycin based on the Investigator examination of the signs and symptoms of the primary ABSSSI; Investigator assessment of clinical cure is complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics is needed	7 to 14 days after end of therapy
>= 20% Reduction in Lesion Area	Clinical response at the ECE visit (48-72 hours following initiation of study drug administration) based on changes in ABSSSI lesion size measurements from baseline.	48-72 hours after the initation of study therapy

Collaborators and Investigators

• Sponsor: Melinta Therapeutics, Inc.
• Investigators: Principal Investigator: G. Ralph Corey, MD, Duke Clinical Research Institute

Publications and helpful links

General Publications

• Corey GR, Loutit J, Moeck G, Wikler M, Dudley MN, O'Riordan W; SOLO I and SOLO II investigators. Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis from the Phase 3 SOLO Studies. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e01919-17. doi: 10.1128/AAC.01919-17. Print 2018 Apr.
• Deck DH, Jordan JM, Holland TL, Fan W, Wikler MA, Sulham KA, Ralph Corey G. Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting. Infect Dis Ther. 2016 Sep;5(3):353-61. doi: 10.1007/s40121-016-0119-9. Epub 2016 Jul 1. Erratum In: Infect Dis Ther. 2016 Sep;5(3):363-5.
• Corey GR, Good S, Jiang H, Moeck G, Wikler M, Green S, Manos P, Keech R, Singh R, Heller B, Bubnova N, O'Riordan W; SOLO II Investigators. Single-dose oritavancin versus 7-10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II noninferiority study. Clin Infect Dis. 2015 Jan 15;60(2):254-62. doi: 10.1093/cid/ciu778. Epub 2014 Oct 6.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (Estimate): December 3, 2010

Study Record Updates

• Last Update Posted (Actual): May 5, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: ABSSSI; Abscess; Skin Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Connective Tissue Diseases; Skin Diseases, Infectious; Suppuration; Inflammation; Infections; Communicable Diseases; Abscess; Cellulitis; Wound Infection; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Oritavancin
• Other Study ID Numbers: TMC-ORI-10-02