Afabicin for Bone or Joint Infection

No longer recruiting at 28 trial locations

Overseen By Debiopharm International S.A

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Debiopharm International SA

Disqualifiers: Liver injury, QT prolongation, 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: Unknown

Duration: 14 days IV, followed by oral treatment

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment, Afabicin, for bone or joint infections caused by specific bacteria, such as Staphylococcus aureus, which are often difficult to treat. The study aims to determine if Afabicin is safe, how it feels to take, and whether it outperforms the usual treatment. Participants will receive either Afabicin or the standard treatment currently used for these infections. Individuals with a bone or joint infection specifically caused by Staphylococcus aureus, who have not had more than a week of antibiotics, might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received more than 7 days of empiric antibiotics before starting the study drug unless the pathogen was resistant. It's best to discuss your current medications with the trial team.

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 the trial coordinators or your doctor.

Is there any evidence suggesting that Afabicin is likely to be safe for humans?

Research shows that afabicin is generally safe for people. Studies have found its safety for treating bone or joint infections caused by staphylococci to be similar to standard treatments. In earlier studies, patients experienced similar recovery rates and safety outcomes compared to usual care. Afabicin has also proven effective and well-tolerated for treating skin infections caused by staphylococci, supporting its continued use. Overall, evidence suggests that afabicin is a safe option for treating these infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care, which often involves long courses of antibiotics like vancomycin or ceftriaxone, Afabicin offers a novel approach to treating bone or joint infections. Afabicin is unique because it specifically targets the bacteria Staphylococcus species, including MRSA, which are common culprits in these infections. This targeted action, combined with its ability to be administered both intravenously and orally, potentially allows for a more streamlined treatment process. Researchers are excited because Afabicin could offer a more effective and convenient option for patients, possibly reducing hospital stays and improving outcomes.

What evidence suggests that Afabicin could be an effective treatment for bone or joint infection?

Research shows that afabicin holds promise for treating bone and joint infections caused by Staphylococcus aureus and other staph bacteria. In this trial, participants will receive either afabicin or the standard of care. Previous studies found that afabicin performs comparably to the usual treatments doctors use. It also penetrates well into bone tissue, which is crucial for treating these infections. Overall, the evidence suggests that afabicin could be an effective option for addressing these persistent staph infections in bones and joints. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for people with bone or joint infections caused by Staphylococcus bacteria, who've had less than a week of antibiotics unless the bug was resistant. They must be able to follow study rules and not have diabetic foot-related infections, other bacterial co-infections, recent serious heart issues, drug/alcohol abuse history in the last year, short life expectancy or risk factors for liver injury or abnormal heart rhythm.

Inclusion Criteria

Able to provide written informed consent and to comply with study procedures

I have a bone or joint infection not caused by diabetes, treated early, and possibly involving soft tissue.

Exclusion Criteria

Life expectancy of less than 1 year.

I have a condition that can cause abnormal heart rhythms.

Documented history of alcohol or drug abuse within the previous 12 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Afabicin IV for up to 14 days followed by oral Afabicin for the remaining treatment duration

14 days IV, followed by oral treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Afabicin

Trial Overview The study tests Afabicin's safety and effectiveness against bone/joint staph infections compared to standard treatments. It's randomized (participants are put into groups by chance) and open-label (everyone knows which treatment they're getting).

How Is the Trial Designed?

Group I: Afabicin Experimental Treatment 1 Intervention

In Part A, afabicin will be given intravenous (IV) at a dose 160 milligrams (mg) twice daily (BID) for a minimum of 1 day (at least 1 dose) and up to a maximum of 14 days (2 weeks), followed by a switch to oral Afabicin at a dose of 240 mg BID for the remaining treatment duration. In Part B, participants will be administered with open label afabicin IV at a dose of 55 mg BID for a minimum of 1 day (at least 1 dose) and up to a maximum of 14 days (2 weeks) followed by a switch to oral afabicin at a dose of 80 mg BID for the remaining treatment duration. In certain study conditions a higher dosing regimen of afabicin might be used: afabicin intravenous (IV) at a dose of 80 mg BID for a minimum of 1 day (at least 1 dose) and up to a maximum of 14 days (2 weeks) followed by a switch to oral afabicin at a dose of 120 mg BID for the remaining treatment duration.

Group II: Standard of Care (SOC) (Parts A and B) Active Control 1 Intervention

Participants will be administered with SOC in accordance with local practice and applicable treatment guidelines without exceeding the maximum dosing schedule.

Who Is Running the Clinical Trial?

Debiopharm International SA

Lead Sponsor

Trials

53

Recruited

7,300+

Published Research Related to This Trial

A meta-analysis of 82 studies found that the incidence of diarrhea and generalized rash varies significantly among different antibiotics used to treat acute otitis media in children, with high-dose amoxicillin/clavulanate showing the highest rates of diarrhea (18.9%) and rash (6.5%).

The way adverse events are reported can influence the incidence rates, suggesting that clinicians should consider both the type of antibiotic and the method of data collection when prescribing treatments for acute otitis media.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Antibiotics Used to Treat Acute Otitis Media in Children: A Systematic Meta-Analysis. Hum, SW., Shaikh, KJ., Musa, SS., et al.[2020]

Afabicin, a novel antibiotic, demonstrated excellent penetration into bone tissues in a study of 17 patients undergoing hip replacement surgery, indicating its potential effectiveness against staphylococcal infections, including methicillin-resistant Staphylococcus aureus.

The concentrations of afabicin desphosphono in bone and synovial fluid exceeded the minimum inhibitory concentration (MIC90) for S. aureus, suggesting that it could effectively treat bone and joint infections caused by this bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery. Menetrey, A., Janin, A., Pullman, J., et al.[2020]

Afabicin desphosphono shows strong potential as a new antibiotic against Staphylococcus aureus, particularly against strains resistant to existing treatments like vancomycin and daptomycin, with a significant reduction in bacterial counts observed in laboratory tests.

The drug accumulates effectively within immune cells, achieving high concentrations that enhance its ability to combat intracellular infections, demonstrating a similar bacteriostatic effect to traditional antibiotics in controlling the growth of phagocytized bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular pharmacokinetics and intracellular activity of the bacterial fatty acid synthesis inhibitor, afabicin desphosphono against different resistance phenotypes of Staphylococcus aureus in models of cultured phagocytic cells. Peyrusson, F., Van Wessem, A., Dieppois, G., et al.[2020]

Acute clavicle osteomyelitis is a rare condition in children, accounting for less than 3% of osteomyelitis cases, and is primarily caused by Staphylococcus aureus, which was found in a 12-year-old patient treated successfully with clindamycin for 6 weeks.

A review of 16 cases showed that while most patients had a good prognosis with a low recurrence rate (6.2%), some required surgical intervention, highlighting the importance of prompt diagnosis and appropriate antimicrobial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rare Case of Clavicle Osteomyelitis in a Child and Literature Review. Chrysochoou, EA., Antachopoulos, C., Badekas, K., et al.[2020]

This study will evaluate whether shorter durations of antibiotic therapy (1 to 3 weeks) for diabetic foot infections (DFI) are as effective as longer durations, with a total of 400 DFI episodes being analyzed from 2019 to 2022.

The primary goal is to determine if these shorter treatments can achieve similar infection remission rates while also reducing adverse events and overall treatment costs, thereby improving patient care and minimizing unnecessary antibiotic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of the antibiotic management of diabetic foot infections: protocol for two randomized controlled trials. Waibel, F., Berli, M., Catanzaro, S., et al.[2022]

Afabicin, a novel antibiotic targeting fatty acid synthesis in Staphylococcus spp., demonstrated comparable efficacy to vancomycin/linezolid in treating acute bacterial skin infections, with clinical response rates of 94.6% for low-dose afabicin and 90.1% for high-dose afabicin.

Both doses of afabicin were well tolerated, with mild side effects like headache and nausea, indicating its potential as a safe treatment option for staphylococcal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afabicin, a First-in-Class Antistaphylococcal Antibiotic, in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Clinical Noninferiority to Vancomycin/Linezolid. Wittke, F., Vincent, C., Chen, J., et al.[2022]

From 2011 to 2015, an estimated 145,490 emergency department visits annually in the U.S. were due to adverse events from antibiotics, highlighting a significant safety concern.

Allergic reactions were the leading cause of these visits, accounting for 74.3% of cases, with younger adults (ages 20-34) experiencing the highest rates of antibiotic-related adverse events compared to older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

National Estimates of Emergency Department Visits for Antibiotic Adverse Events Among Adults-United States, 2011-2015. Geller, AI., Lovegrove, MC., Shehab, N., et al.[2020]

A study analyzing adverse drug events related to antibiotics in Brazil from December 2018 to December 2021 identified 294 safety signals, with azithromycin leading in the number of signals (49), highlighting the importance of monitoring antibiotic safety.

Serious adverse events were linked to ceftazidime and avibactam, a new drug, and unexpected issues like suicide attempts were associated with amoxicillin/clavulanate, indicating the need for careful evaluation of antibiotic safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential safety signals for antibacterial agents from the Brazilian national pharmacovigilance database (Vigimed/VigiFlow). Barbosa, LHLA., Silva, ARO., Carvalho-Assef, APD., et al.[2022]

Afabicin, a new antibiotic, showed no significant impact on the gut microbiota diversity or richness in both mice and healthy human volunteers after a 10-day treatment, indicating its potential for microbiome preservation.

In contrast to standard antibiotics like clindamycin, linezolid, and moxifloxacin, which caused significant dysbiosis in mice, afabicin maintained a stable gut microbiota, suggesting it may be a safer option for preserving healthy gut bacteria during antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin. Nowakowska, J., Cameron, DR., De Martino, A., et al.[2023]

Clarithromycin is well tolerated and shows no adverse effects on fertility or reproduction in animal studies, indicating a favorable safety profile for use in humans.

In clinical trials involving 3768 patients, common side effects like nausea and diarrhea were mild and reversible, with adverse reaction rates comparable to or lower than other antibiotics, suggesting clarithromycin is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the tolerability profile of clarithromycin in preclinical and clinical trials. Guay, DR., Patterson, DR., Seipman, N., et al.[2018]

Macrolide antibacterials are considered one of the safest classes of antibiotics, with severe adverse reactions being rare, and recent derivatives show even fewer gastrointestinal side effects compared to older compounds like erythromycin.

While gastrointestinal disturbances are common, newer macrolides like azithromycin and clarithromycin have significantly lower rates of these effects (5% or fewer) and a low hepatotoxic potential, making them safer options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of macrolide antibacterials. Periti, P., Mazzei, T., Mini, E., et al.[2018]

Citations

1. academic.oup.com academic.oup.com/ofid/article/doi/10.1093/ofid/ofae631.272/7988477

P-65. Results from A Phase 2 Clinical Trial for Treatment of ... The clinical response rate and safety profile of 2-3 weeks treatment of staphylococcal BJI with afabicin was comparable to SoC. These data ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03723551

NCT03723551 | Study to Assess Safety, Tolerability and ... This is a randomized, active-controlled, open-label study to assess the safety, tolerability and efficacy of Afabicin in the treatment of participants with bone ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6395911/

Bone and Joint Tissue Penetration of the Staphylococcus ... The study showed good penetration of afabicin desphosphono into bone tissues, with mean area under the curve ratios for cortical bone-, cancellous bone-, bone ...

4. contagionlive.com contagionlive.com/view/early-stage-antibiotic-for-bone-and-joint-infections-comparable-to-standard-of-care-therapy

Early-Stage Antibiotic for Bone and Joint Infections ... “The clinical response rate and safety profile of 2-3 weeks treatment of staphylococcal BJI with afabicin was comparable to SoC. These data ...

5. debiopharm.com debiopharm.com/pipeline/afabicin-debio-1450

afabicin (Debio 1450) Results from A Phase 2 Clinical Trial for Treatment of Bone And Joint Infections with Afabicin, A First-in-Class Selective Anti-Staphylococcal… Read more.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7508579/

Afabicin, a First-in-Class Antistaphylococcal Antibiotic, in the ... Afabicin was efficacious and well tolerated in the treatment of ABSSSI due to staphylococci, and these data support further development of afabicin for the ...