Linezolid for Syphilis Pilot Study

Pilot Study of Linezolid for Early Syphilis Treatment

The study aims to evaluate the efficacy of linezolid for the treatment of syphilis.

Study Overview

• Status: Recruiting
• Conditions: Syphilis
• Intervention / Treatment: Drug: Group B, Linezolid 10d; Drug: Group A, Penicillin

Detailed Description

This will be a randomized, open-label, non-comparative, adaptive pilot trial to evaluate the efficacy of linezolid 600mg orally, twice a day, for five or ten days, using a contemporaneous historical control group benzathine penicillin G (single dose of 2.4 million units) in participants with and without HIV infection.

In total, 24 participants will be enrolled across multiple clinical sites in the United States. Participants will participate in follow-ups to monitor clinical outcomes and serological response (RPR titer) at 1 month, 3 months, and 6 months.

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 Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jeffrey D Klausner, MD MPH; Phone Number: (415) 876-8901; Email: jdklausner@med.usc.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Recruiting
      • Howard Brown Health
      • Contact: Catherine Creticos, MD
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • Open Arms Healthcare Center
      • Contact: Keith Stokes, MD

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Other Names: zyvox
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; Other Names: bicillin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to Treatment	Percentage of linezolid participants with a 4-fold decrease or greater in the serum RPR titer by 180 days after treatment	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treponema pallidum susceptibility	Determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of linezolid against 6 historical and 3 clinical isolated strains	6 months

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: The University of Texas Health Science Center, Houston; Universidad Peruana Cayetano Heredia
• Investigators: Principal Investigator: Jeffrey D Klausner, MD MPH, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 16, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Penicillin; Linezolid; Treponema pallidum; Early Syphilis
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sexually Transmitted Diseases, Bacterial; Spirochaetales Infections; Treponemal Infections; Urogenital Diseases; Genital Diseases; Syphilis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid; Penicillins
• Other Study ID Numbers: APP-22-04165

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared with other researchers

Drug and device information, study documents

• 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