Linezolid for Syphilis Pilot Study

• ClinicalTrials.gov Identifier: NCT05548426
• Recruitment Status: Not yet recruiting
• First Posted: September 21, 2022
• Last Update Posted: October 28, 2022
• Sponsor: University of Southern California
• Collaborators: Universidad Peruana Cayetano Heredia; The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Jeffrey Klausner, University of Southern California

Study Description

Brief Summary:

The two specific aims are: AIM 1: To evaluate the efficacy of linezolid compared to benzathine penicillin G in the treatment of syphilis. AIM 2: Evaluate the susceptibility of Treponema pallidum historical and novel strains to linezolid.

Condition or disease	Intervention/treatment	Phase
Syphilis	Drug: Group C, Linezolid 5; Drug: Group B, Linezolid 10d; Drug: Group A, Penicillin	Early Phase 1

Detailed Description:

This will be a randomized, open-label, non-comparative, adaptive pilot trial to evaluate the efficacy of two linezolid oral dosing schemes (600mg orally, twice a day, for five or ten days) compared to the current recommendation for the treatment of syphilis, benzathine penicillin G (single dose of 2.4 million units) in participants with and without HIV infection. In total, 60 participants will be enrolled across 2 clinical sites in Peru. Participants will participate in follow-ups to monitor clinical outcomes and serological response (RPR titer) at 1 month, 3 months, and 6 months. The investigators will also test linezolid against several types of syphilis strains in the lab to evaluate the microbicidal activity of linezolid in treating early syphilis. Study findings may identify an efficacious alternative syphilis treatment to penicillin that is effective for people living with HIV. Study findings may also help address the crisis of penicillin shortages, difficulty in administration, and offer options for those with penicillin allergy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Linezolid for Early Syphilis Treatment
• Estimated Study Start Date: April 2023
• Estimated Primary Completion Date: March 2025
• Estimated Study Completion Date: March 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Linezolid 5 Day; Oral Linezolid 600mg, taken twice a day for 5 days	Drug: Group C, Linezolid 5; Oral Linezolid 600mg, taken twice a day for 5 days
Experimental: Linezolid 10 Day; Oral linezolid 600mg, taken twice a day for 10 days	Drug: Group B, Linezolid 10d; Oral Linezolid 600mg, taken twice a day for 10 days
Active Comparator: Benzathine Penicillin G; Single intramuscular injection of 2.4 million units of benzathine penicillin G	Drug: Group A, Penicillin; Standard of care benzathine penicillin G, one intramuscular injection, 2.4MU

Outcome Measures

Primary Outcome Measures :

1. Response to Treatment [ Time Frame: 6 months ]
   Percentage of linezolid participants with a 4-fold decrease or greater in the serum RPR titer by 180 days after treatment

Secondary Outcome Measures :

1. Treponema pallidum susceptibility [ Time Frame: 6 months ]
   Determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of linezolid against 6 historical and 3 clinical isolated strains

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 16 years of age or older
• Diagnosed cases of primary, secondary, or early latent syphilis with RPR titer ≥1:8 within 3 weeks prior to enrollment
• Able to provide informed consent
• For PLHIV: on treatment for HIV-infection and most recent viral load <200 copies/mL or most recent CD4 T-cell count >350 cells/mL

Exclusion Criteria:

• Pregnancy or a positive pregnancy test on the day of enrollment
• Participants who receive certain psychotropic medications, e.g., MAO inhibitors, SNRIs, SSRIs
• Patients showing signs and symptoms of neurosyphilis
• Serofast RPR titer
• Recent (<7 days) or concomitant antimicrobial therapy with azithromycin, doxycycline, ceftriaxone, cefixime, or other beta lactam antibiotics (e.g. amoxicillin)
• Linezolid or penicillin allergy

Contacts and Locations

Contacts

Contact: Jeffrey D Klausner, MD MPH; (415) 876-8901; jdklausner@med.usc.edu

Sponsors and Collaborators

University of Southern California

Universidad Peruana Cayetano Heredia

The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Jeffrey D Klausner, MD MPH; University of Southern California

More Information

• Responsible Party: Jeffrey Klausner, Clinical Professor, University of Southern California
• ClinicalTrials.gov Identifier: NCT05548426
• Other Study ID Numbers: APP-22-04165
• First Posted: September 21, 2022
• Last Update Posted: October 28, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No IPD will be shared with other researchers

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Jeffrey Klausner, University of Southern California:

Linezolid; Treponema pallidum; Penicillin; Early Syphilis

Additional relevant MeSH terms:

Syphilis; Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases; Linezolid; Penicillins; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action