Oritavancin for Skin Infections

Recruiting at 26 trial locations

Overseen By Sandra George

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Melinta Therapeutics, Inc.

Must not be taking: Glycopeptides, Dalbavancin, Heparin, Warfarin

Disqualifiers: Septic shock, Neutropenia, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Single dose

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol describes a randomized, open-label study to evaluate the safety and tolerability of single-dose intravenous (IV) oritavancin diphosphate (oritavancin) versus standard of care (SoC) antibiotics for the treatment of pediatric subjects with acute bacterial skin and skin structure infections (ABSSSIs). This study involves two oritavancin products, ORBACTIV® and KIMYRSATM. Oritavancin is the active drug substance in both ORBACTIV and KIMYRSA. This study protocol distinguishes the differences between ORBACTIV and KIMYRSA by providing product-specific data, and information and guidance for Investigators. "Oritavancin" is used to describe drug product data, and information and guidance that is not specific to ORBACTIV or KIMYRSA (i.e., applies to both). The study involves pharmacokinetic (PK) sampling and will evaluate clinical outcome assessments. The study was designed to capture adequate data while minimizing the impact to subjects and their caregivers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken certain antibiotics recently or are on specific medications like heparin or warfarin. It's best to discuss your current medications with the study team to see if they might affect your eligibility.

What data supports the effectiveness of the drug Oritavancin for skin infections?

Oritavancin is a drug approved by the FDA for treating acute bacterial skin and skin structure infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It has been shown to be effective as a single-dose treatment against Gram-positive bacteria, which are common causes of these infections. ^{1 2 3 4 5}

What makes the drug Oritavancin unique for treating skin infections?

Oritavancin is unique because it can be given as a single-dose IV treatment, thanks to its long half-life, and it works by multiple mechanisms to kill bacteria, including those resistant to other antibiotics like methicillin-resistant Staphylococcus aureus (MRSA). ^{3 4 6 7 8}

Eligibility Criteria

This trial is for children aged 3 months to under 18 years with certain bacterial skin infections. They must have symptoms like wound infection, cellulitis, or abscesses caused by gram-positive bacteria. Kids can't join if they've had extensive prior antibiotic treatment, severe kidney issues, allergic reactions to similar drugs, are on blood thinners or immunosuppressants, or have certain viral infections.

Inclusion Criteria

I have a serious skin infection like a wound, cellulitis, or a large abscess.

I have at least two symptoms of a severe skin infection.

Written informed consent obtained from parent(s) or legal guardian(s), with written or documented verbal assent of the child obtained, when appropriate, before initiation of any assessments conducted solely for study purposes

Exclusion Criteria

I am willing to use two forms of birth control or practice abstinence during the study.

I have been treated with antibiotics for a skin infection for more than 72 hours.

I have taken a glycopeptide antibiotic within the last 24 hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single-dose intravenous (IV) oritavancin or standard of care antibiotics for the treatment of acute bacterial skin and skin structure infections

Single dose

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including clinical outcome assessments at End of Treatment and Test of Cure visits

28 days

2 visits (in-person)

Treatment Details

Interventions

• Oritavancin

Trial Overview The study tests the safety of a single IV dose of Oritavancin (found in ORBACTIV and KIMYRSA) against standard antibiotics for treating pediatric acute bacterial skin infections. It's an open-label study that includes pharmacokinetic sampling and clinical outcome assessments.

Participant Groups

Group I: Orbactiv Experimental Treatment 1 Intervention

ORBACTIV is infused at 15mg/kg over 3 hours for all subjects not to exceed a dose of 1200mg.

Group II: Kimyrsa Experimental Treatment 1 Intervention

* KIMYRSA is infused at 15mg/kg over 1 hour for subjects ≥12 years old and weighing \>40 kg not to exceed a dose of 1200mg. * KIMYRSA is infused at 15mg/kg over 3 hours in subjects \<12 years old or weighing ≤40 kg.

Group III: Standard of Care Active Control 1 Intervention

The following SoC medications below will be administered via IV infusion, per the package insert, and according to local rules and regulations. SoC medications cannot be used in combination with one another. * Vancomycin * Teicoplanin * Clindamycin * Daptomycin * Semi-synthetic penicillins (e.g., nafcillin, oxacillin, cloxacillin) * Cefazolin * Ceftaroline

Oritavancin is already approved in United States, European Union for the following indications:

Approved in United States as Orbactiv/Kimyrsa for:

• Acute bacterial skin and skin structure infections

Approved in European Union as Orbactiv/Kimyrsa for:

• Acute bacterial skin and skin structure infections

Who Is Running the Clinical Trial?

Melinta Therapeutics, Inc.

Lead Sponsor

Trials

36

Recruited

9,600+

Melinta Therapeutics, LLC

Lead Sponsor

Trials

3

Recruited

250+

Findings from Research

Oritavancin is a lipoglycopeptide antibiotic specifically designed for treating acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive bacteria, and it was first approved in the US in August 2014.

The development of oritavancin represents a significant advancement in antibacterial treatments, providing a single-dose option for patients with ABSSSI, which simplifies treatment regimens and may improve patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oritavancin: first global approval. Markham, A.[2021]

Oritavancin, a second-generation lipoglycopeptide, has been shown to be as effective as vancomycin in treating Acute Bacterial Skin and Skin Structure Infections caused by Gram-positive bacteria, including MRSA, with a similar safety profile.

The main advantage of oritavancin is its single-dose administration and no need for plasma level monitoring, which could facilitate outpatient treatment, although its cost-effectiveness compared to other treatments remains to be fully established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of oritavancin for the treatment of acute bacterial skin and skin structure infections. García Robles, AA., López Briz, E., Fraga Fuentes, MD., et al.[2019]

Oritavancin is a new-generation lipoglycopeptide antibiotic specifically designed to treat acute bacterial skin and skin structure infections.

It offers a novel treatment option that may improve patient outcomes due to its unique mechanism of action against resistant bacterial strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oritavancin (Orbactiv): A New-Generation Lipoglycopeptide for the Treatment Of Acute Bacterial Skin and Skin Structure Infections. Rosenthal, S., Decano, AG., Bandali, A., et al.[2020]

Oritavancin, a single-dose IV therapy, was shown to be effective in treating acute bacterial skin infections, with only 6.1% of patients requiring hospitalization within 30 days after outpatient treatment, indicating its potential to reduce hospital admissions.

In a cohort of patients discharged from hospitals, the 30-day readmission rate was low at 6.6%, with only 2.6% related to infections, suggesting that oritavancin can safely facilitate early discharge for patients with skin and soft tissue infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Real-World Economic and Clinical Management of Adult Patients with Skin and Soft Tissue Infections (SSTIs) with Oritavancin: Data from Two Multicenter Observational Cohort Studies. Estrada, S., Lodise, TP., Tillotson, GS., et al.[2020]

Oritavancin demonstrated high efficacy against Gram-positive pathogens responsible for skin and soft-tissue infections, with 98.8% of tested isolates being susceptible, including low MIC values for Staphylococcus aureus and various Streptococcus species.

Even against vancomycin-resistant Enterococcus faecalis, oritavancin was effective, inhibiting all strains at concentrations ≤0.5 mg/L, indicating its potential as a treatment option for resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of oritavancin against Gram-positive clinical isolates responsible for documented skin and soft-tissue infections in European and US hospitals (2010-13). Mendes, RE., Farrell, DJ., Sader, HS., et al.[2018]

In a study of 17 patients receiving multiple doses of oritavancin for complicated infections, all patients achieved clinical success or improvement, indicating its efficacy in treating serious infections like osteomyelitis and pneumonia.

While 24% of patients experienced adverse events that required discontinuation of oritavancin, these events were reversible, suggesting that oritavancin may be a safe alternative to traditional daily antibiotic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple-Dose Oritavancin Evaluation in a Retrospective Cohort of Patients with Complicated Infections. Schulz, LT., Dworkin, E., Dela-Pena, J., et al.[2018]

Oritavancin is a powerful new antibiotic effective against serious Gram-positive infections, including methicillin-resistant Staphylococcus aureus, with a unique ability to work through multiple mechanisms of action.

It has a long half-life that may allow for infrequent dosing, potentially enabling treatment with just a single dose, while also demonstrating documented clinical efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oritavancin for skin infections. Anderson, DL.[2018]

Oritavancin is effective against a wide range of Gram-positive bacteria, including multidrug-resistant strains, with comparable or lower minimum inhibitory concentrations (MICs) than vancomycin and daptomycin, indicating its potential as a strong treatment option for acute bacterial skin infections.

In a study involving over 11,000 clinical isolates from 2011 to 2014, oritavancin showed equivalent in vitro activity against both meticillin-resistant and meticillin-susceptible Staphylococcus aureus, demonstrating its efficacy across different bacterial strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of oritavancin and comparator agents against staphylococci, streptococci and enterococci from clinical infections in Europe and North America, 2011-2014. Biedenbach, DJ., Arhin, FF., Moeck, G., et al.[2018]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Oritavancin: first global approval. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

Review of oritavancin for the treatment of acute bacterial skin and skin structure infections. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Oritavancin (Orbactiv): A New-Generation Lipoglycopeptide for the Treatment Of Acute Bacterial Skin and Skin Structure Infections. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Real-World Economic and Clinical Management of Adult Patients with Skin and Soft Tissue Infections (SSTIs) with Oritavancin: Data from Two Multicenter Observational Cohort Studies. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Activity of oritavancin against Gram-positive clinical isolates responsible for documented skin and soft-tissue infections in European and US hospitals (2010-13). [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Multiple-Dose Oritavancin Evaluation in a Retrospective Cohort of Patients with Complicated Infections. [2018]

7. Spain pubmed.ncbi.nlm.nih.gov

Oritavancin for skin infections. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro activity of oritavancin and comparator agents against staphylococci, streptococci and enterococci from clinical infections in Europe and North America, 2011-2014. [2018]