Abscess, Cellulitis, Systemic Inflammation, Wound Infection
Conditions
Keywords
ABSSSI, Skin Infection, Abscess
Brief summary
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.
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.
Interventions
Intravenous oritavancin and IV placebo or IV vancomycin will be administered for a minimum of 7 days up to a maximum of 10 days.
DRUGIV 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.
Sponsors
Melinta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Clinical Response | 48-72 hours after the initation of study therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint) | 7 to 14 days after end of therapy | 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 |
| >= 20% Reduction in Lesion Area | 48-72 hours after the initation of study therapy | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single-Dose 1200 mg Oritavancin Single 1200 mg IV Dose of Oritavancin Diphosphate administered as first infusion followed by IV placebo administered twice daily for a minimum of 7 days up to a maximum of 10 days. | 503 |
| Vancomycin IV Vancomycin, 1g or 15mg/kg administered twice daily for a minimum of 7 days up to a maximum of 10 days. | 502 |
| Total | 1,005 |
Baseline characteristics
| Characteristic | Single-Dose 1200 mg Oritavancin | Vancomycin | Total |
|---|---|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 13.4 | 44.4 years STANDARD_DEVIATION 14.29 | 44.7 years STANDARD_DEVIATION 13.85 |
| Sex: Female, Male Female | 165 Participants | 159 Participants | 324 Participants |
| Sex: Female, Male Male | 338 Participants | 343 Participants | 681 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 272 / 503 | 265 / 502 |
| serious Total, serious adverse events | 22 / 503 | 23 / 502 |
Outcome results
Primary
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.
Time frame: 48-72 hours after the initation of study therapy
Population: Modified intent to treat (mITT) population consisting of all patients randomized into the trial and received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single-Dose 1200 mg Oritavancin | Early Clinical Response | Success | 403 participants |
| Single-Dose 1200 mg Oritavancin | Early Clinical Response | Failure | 100 participants |
| Vancomycin | Early Clinical Response | Success | 416 participants |
| Vancomycin | Early Clinical Response | Failure | 86 participants |
95% CI: [-7.5, 2]
Secondary
>= 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.
Time frame: 48-72 hours after the initation of study therapy
Population: Modified intent to treat (mITT) population consisting of all patients randomized into the trial and received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single-Dose 1200 mg Oritavancin | >= 20% Reduction in Lesion Area | Success | 432 participants |
| Single-Dose 1200 mg Oritavancin | >= 20% Reduction in Lesion Area | Failure | 71 participants |
| Vancomycin | >= 20% Reduction in Lesion Area | Success | 428 participants |
| Vancomycin | >= 20% Reduction in Lesion Area | Failure | 74 participants |
95% CI: [-3.7, 5]
Secondary
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
Time frame: 7 to 14 days after end of therapy
Population: Modified intent to treat (mITT) population consisting of all patients randomized into the trial and received any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single-Dose 1200 mg Oritavancin | Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint) | Clinical Cure | 416 participants |
| Single-Dose 1200 mg Oritavancin | Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint) | Clinical Failure | 87 participants |
| Vancomycin | Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint) | Clinical Cure | 404 participants |
| Vancomycin | Investigator Assessed Clinical Cure at Post Therapy Evaluation (Key Secondary Endpoint) | Clinical Failure | 98 participants |
95% CI: [-2.6, 7]