Omadacycline for Bone and Joint Infections

(CORGI Trial)

Recruiting at 1 trial location

Overseen By Donna Phan Tran, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Must not be taking: Tetracyclines

Disqualifiers: Pregnancy, Fungi, Mycobacteria, Endocarditis, 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

Compensation: Varies

Number of Visits: 1

Duration: 4-12 weeks

180 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with your doctor to understand how your current medications might interact with the trial treatment.

What data supports the effectiveness of the drug Omadacycline for bone and joint infections?

While there is no direct evidence for Omadacycline in bone and joint infections, studies show that many antibiotics, including those similar to Omadacycline, can penetrate bone and joint tissues effectively, suggesting potential usefulness in such infections. ^{1 2 3 4 5}

Is Omadacycline safe for humans?

Omadacycline has a favorable safety profile, with the most common side effects being mild stomach-related symptoms. It has minimal interactions with other drugs and does not require dose adjustments based on age, sex, or liver and kidney function. ^{6 7 8 9 10}

How is the drug Omadacycline unique for treating bone and joint infections?

Omadacycline is unique because it is a newer antibiotic that may offer better penetration into bone and joint tissues compared to some traditional antibiotics, potentially making it more effective in treating infections in these areas. ^{1 2 3 4 11}

What is the purpose of this trial?

The study design is a randomized, open-label, clinical trial of omadacycline vs Standard of Care (SOC) antibiotics for bone and join infection (BJI) treatment. Study participants will have their BJI regimen chosen by their treating physicians, (typically Infectious Diseases for hardware and prosthetic joint infections, or multidisciplinary Limb Salvage team for diabetic foot infections) prior to enrollment. Then participants will be randomized to an omadacycline-containing regimen versus the a priori chosen SOC regimen. Participants must require between 4 and 12 weeks of therapy for their BJI. The exact duration of therapy will be decided by the participants' treating physician. At 12 weeks, if the treating physician wishes to extend therapy, participants receiving omadacycline will be transitioned to other SOC antibiotics. Once enrolled, participants will be followed via in-person clinic visits at the following intervals: weeks 0, 2, 4, 8, and 12. A final in-person visit will occur 2 weeks post-treatment completion. A phone survey will occur 3 months post-treatment completion. Participants in the SOC group will follow the same schedule. Oral once-daily dosing options for S. aureus and Coagulase negative Staphylococcus are essentially non-existent. Thus, omadacycline possesses a novel and advantageous option for BJI treatment. Its convenient dosing regimen will almost certainly be associated with improved adherence, and higher adherence may, in turn, improve clinical outcome. Investigators hypothesize that omadacycline will be a well-tolerated and efficacious oral antibiotic for BJIs and will be associated with improved adherence compared with standard of care oral antibiotics. Investigators believe omadacycline addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for use as a prolonged therapy for BJIs. To this aim, investigators will perform a randomized, open-label clinical trial of omadacycline to SOC antibiotics for BJIs.

Research Team

Loren G Miller

Principal Investigator

The Lundquist Institute For Biomedical Innovation at Harbor-UCLA Medical Center

Amy Y. Kang, PharmD, BCIDP

Principal Investigator

Chapman Univeristy

Eligibility Criteria

Adults aged 18-85 with bone and joint infections (BJI) suspected to be caused by gram-positive bacteria, needing 4-12 weeks of outpatient treatment. Participants must be able to take oral medication and attend clinic visits. Women of childbearing age must use two forms of contraception during the study.

Inclusion Criteria

I can attend all required follow-up visits at the research clinic.

If a woman is of childbearing potential, she must consistently use two acceptable methods of contraception (IUD, injectable contraceptive, birth control patch, OCP, barrier method, abstinence) from baseline through the course of antibiotics (4-12 weeks). If a male patient's sexual partner is of childbearing potential, the male patient must acknowledge that they will consistently use an acceptable method of contraception as defined above from baseline through the course of antibiotics (4-12 weeks)

I am on a short-term antibiotics course, not for chronic use.

Exclusion Criteria

Pregnancy or breast feeding. Women of childbearing potential must have a negative urine or serum pregnancy test result within 1 day prior to initiation of study drug

I have completed both surgeries and 6 weeks of IV therapy for my prosthetic joint infection.

My bone and joint infection is complicated by heart infection or brain abscesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either omadacycline or standard of care antibiotics for bone and joint infections, with therapy lasting between 4 and 12 weeks as decided by the treating physician.

4-12 weeks

In-person visits at weeks 0, 2, 4, 8, and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a final in-person visit 2 weeks post-treatment and a phone survey 3 months post-treatment.

16-24 weeks

1 in-person visit, 1 phone survey

Extension

If necessary, participants may transition to other standard of care antibiotics after 12 weeks of omadacycline treatment.

Treatment Details

Interventions

• Omadacycline
• Standard of Care

Trial Overview This trial is testing omadacycline pills against standard antibiotics for treating BJIs. Patients' treatments are chosen before they join, then randomly assigned to either the new pill or their pre-chosen standard care, followed up through clinic visits and phone surveys.

Participant Groups

Group I: standard of care antibiotic Experimental Treatment 1 Intervention

Standard of care as determined by primary care team

Group II: omadacycline Experimental Treatment 1 Intervention

Omadacycline will be administered 300 mg orally daily without the loading dose. We chose to omit the loading dose given that many of the enrolled subjects would have received an IV therapy prior to omadacycline initiation and notable gastrointestinal intolerabilities (nausea/vomiting) based on Phase-3 trial data. Subjects receiving omadacycline will be counseled on appropriate timing of administration (fast for 4 hours before dosing and no food for 2 hours after dosing) in light of the known food effects on drug absorption. They will be instructed to avoid use of products containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations such as dairy, antacids, and multivitamins for 4 hours post-dosing.

Omadacycline is already approved in United States for the following indications:

Approved in United States as Nuzyra for:

• Community-acquired bacterial pneumonia
• Acute bacterial skin and skin structure infections

Who Is Running the Clinical Trial?

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

Paratek Pharmaceuticals Inc

Industry Sponsor

Trials

17

Recruited

4,000+

Chapman University

Collaborator

Trials

10

Recruited

920+

Findings from Research

A multidisciplinary team developed evidence-based algorithms for antibiotic therapy in bone and joint infections (BJIs), addressing various clinical scenarios such as vertebral osteomyelitis and prosthetic joint infections.

The algorithms consider important factors like the spectrum of antibiotic activity, pharmacokinetics, and the ability to penetrate bone, aiming to improve treatment outcomes for patients with BJIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic considerations for optimizing antimicrobial therapy used to treat bone and joint infections: an evidence-based algorithmic approach. Gatti, M., Tedeschi, S., Zamparini, E., et al.[2023]

Linezolid, daptomycin, and telavancin show potential as treatment options for osteomyelitis caused by resistant gram-positive bacteria, with linezolid demonstrating significant bone penetration in human studies, but its use may be limited by side effects.

Daptomycin and telavancin may serve as alternatives to vancomycin for treating osteomyelitis, while tigecycline and ceftaroline lack sufficient clinical data and show poor bone penetration, limiting their effectiveness in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of newer gram-positive antibiotics in the setting of osteomyelitis of adults. Moenster, RP., Linneman, TW., Call, WB., et al.[2013]

Treating bone and joint infections is challenging and typically requires a combination of long-term antibiotic therapy and surgery, but there is no standardized approach for these treatments.

Due to the lack of high-quality clinical evidence, it is difficult to provide clear, evidence-based recommendations for the optimal antimicrobial therapy, which must be tailored to both the specific microorganisms involved and the individual patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antibiotic therapy of osteoarticular infections in the adult]. Galpérine, T., Bernard, L.[2007]

A review of over 30 antibiotics showed that most, including amoxicillin, vancomycin, and fluoroquinolones, effectively penetrate bone and joint tissues, reaching concentrations that exceed the minimum inhibitory concentrations (MIC) for common pathogens associated with infections.

However, some antibiotics like penicillin and metronidazole demonstrated poor penetration into bone and joint spaces, suggesting they may be less effective for treating these types of infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic penetration into bone and joints: An updated review. Thabit, AK., Fatani, DF., Bamakhrama, MS., et al.[2019]

Tetracycline antibiotics, especially minocycline, significantly reduce disease activity in rheumatoid arthritis (RA) after 3 months of treatment, with a notable effect on tender joint count and inflammatory markers like ESR.

There was no increased risk of adverse events associated with tetracyclines, indicating they are a safe option for RA treatment, although they did not show benefits in preventing radiological progression of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstrates clinical benefit with reduction in disease activity. Stone, M., Fortin, PR., Pacheco-Tena, C., et al.[2013]

Omadacycline, approved by the FDA in 2018, is an effective new antibiotic for treating community-acquired pneumonia and acute bacterial skin infections, showing promise against a wide range of bacteria.

This drug is a semisynthetic derivative of minocycline that can overcome common bacterial resistance mechanisms, making it a valuable option in the fight against resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: A Newly Approved Antibacterial from the Class of Tetracyclines. Durães, F., Sousa, E.[2020]

Omadacycline (NUZYRA™) is a newly approved oral and intravenous antibiotic that effectively treats community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults.

This first-in-class aminomethylcycline antibiotic has a broad spectrum of antibacterial activity, marking a significant advancement in the treatment options available for various bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: First Global Approval. Markham, A., Keam, SJ.[2020]

Omadacycline is a newly approved antibiotic effective against a wide range of bacteria, including drug-resistant strains like MRSA, making it a valuable option for treating community-acquired pneumonia and skin infections.

It has a favorable safety profile with minimal drug interactions, and the most common side effects are gastrointestinal symptoms, indicating it is generally well-tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: A Novel Tetracycline Derivative With Oral and Intravenous Formulations. Watkins, RR., Deresinski, S.[2020]

Omadacycline is a new antibiotic derived from the tetracycline class that remains effective against many resistant bacteria, making it a promising option for treating community-acquired infections like skin infections and pneumonia.

It has a favorable safety profile similar to other tetracyclines, does not require dose adjustments for different patient demographics, and can be taken orally, which may lower hospitalization costs compared to intravenous antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omadacycline: A Modernized Tetracycline. Gallagher, JC.[2023]

Omadacycline is an effective antibiotic against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus, as demonstrated in a study using a neutropenic murine thigh model.

The study found specific pharmacodynamic parameters, with AUC/MIC values of 21.9 for net stasis and 57.7 for a 1-log kill, indicating the concentration levels needed for effective bacterial control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Pharmacodynamics of Omadacycline against Staphylococcus aureus in the Neutropenic Murine Thigh Infection Model. Lepak, AJ., Zhao, M., Marchillo, K., et al.[2020]

In a study of 39 patients with Staphylococcus aureus periprosthetic joint infections, oral doxycycline as suppressive antibiotic therapy showed good tolerability, with only 15.4% experiencing adverse events, and 74.4% remaining free of complications after treatment.

Doxycycline demonstrated effectiveness in managing these infections, with 25.6% of patients experiencing treatment failure, primarily due to relapses related to doxycycline-susceptible pathogens, indicating it can be a viable option for patients at high risk of infection failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients. Pradier, M., Nguyen, S., Robineau, O., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic considerations for optimizing antimicrobial therapy used to treat bone and joint infections: an evidence-based algorithmic approach. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The potential role of newer gram-positive antibiotics in the setting of osteomyelitis of adults. [2013]

3. France pubmed.ncbi.nlm.nih.gov

[Antibiotic therapy of osteoarticular infections in the adult]. [2007]

4. Canada pubmed.ncbi.nlm.nih.gov

Antibiotic penetration into bone and joints: An updated review. [2019]

5. Canada pubmed.ncbi.nlm.nih.gov

Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstrates clinical benefit with reduction in disease activity. [2013]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Omadacycline: A Newly Approved Antibacterial from the Class of Tetracyclines. [2020]

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

Omadacycline: First Global Approval. [2020]

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

Omadacycline: A Novel Tetracycline Derivative With Oral and Intravenous Formulations. [2020]

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

Omadacycline: A Modernized Tetracycline. [2023]

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

In Vivo Pharmacodynamics of Omadacycline against Staphylococcus aureus in the Neutropenic Murine Thigh Infection Model. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients. [2018]