Testing a new antibiotic for treating syphilis

Oral and Neuro-Penetrative Alternative Antibiotics for Patients With Syphilis

This study is testing a new antibiotic called Linezolid to see if it works better than the standard treatment for early syphilis in adults, especially for those who might have complications affecting their nervous system.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 224 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia (Academic / other)
• Locations: 6 sites (Barcelona and 5 other locations)
• Trial ID: NCT05069974 on ClinicalTrials.gov

What this trial studies

The Trep-AB clinical trial aims to evaluate the effectiveness of Linezolid (LZD), a neuropenetrative antibiotic, compared to the standard treatment of Benzathine penicillin G (BPG) for early syphilis. This randomized controlled trial will involve adults diagnosed with primary, secondary, or early latent syphilis. The study is motivated by the limitations of BPG, which does not effectively penetrate the central nervous system, where the syphilis-causing bacteria, Treponema pallidum, can reside. By investigating LZD, the trial seeks to provide a more effective treatment option for patients, particularly those at risk of neurological complications.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 years or older with a diagnosis of primary, secondary, or early latent syphilis.

Not a fit: Patients with late latent syphilis or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective oral treatment for syphilis that penetrates the central nervous system.

How similar studies have performed: While the use of Linezolid for treating syphilis is a novel approach, preclinical studies have shown promising results with this antibiotic against Treponema pallidum.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or older at baseline visit.
2. Primary, secondary or early latent syphilis diagnosis based on SEIMC/IUSTI Guidelines\*

   1. Primary syphilis is defined as typical ulcer (chancre) and positive test using darkfield examination (DFE) or Polymerase chain reaction (PCR) detection of T.p. with/without positive serological test for syphilis.
   2. Secondary syphilis is defined based on typical clinical symptoms with positive treponemal and non-treponemal tests.
   3. Early latent syphilis is defined as positive serological treponemal and non-treponemal tests with no clinical evidence of infection, with a previous negative syphilis serology,or a four-fold increase in RPR titer of a non-treponemal test within the past 12 months.Serological tests for syphilis performed within 10 days prior to study inclusion visit willbe acceptable for enrollment.
3. Signature of written informed consent.
4. Ability to comply with the requirements of the study protocol.
5. If women of childbearing potential, use of a highly effective method of contraception (abstinence,hormonal contraception, intra-uterine device \[IUD\], or anatomical sterility in self or partner)committed during 1 week after last IMP administration.
6. If men, use of condom during heterosexual intercourse and use of a highly effective method ofcontraception (abstinence, hormonal contraception, intra-uterine device \[IUD\], or anatomical sterilityin self or partner) in female partner committed during 1 week after last IMP administration.

   * For inclusion purposes, positive point of care tests (POCT) will be accepted in selected patients without previous syphilis history and negative serological tests for syphilis during the last 12 months (Syphilis rapid diagnostic test \[RDT\] or Chembio DPP syphilis screen \& confirm assay \[DPP\]), or with a previous history of syphilis and negative non-treponemal tests during the last 12 months (DPP). Further confirmation by the methods described in a), b) or c) will benecessary.

Exclusion Criteria:

1. Known allergy to any of the IMPs and/or excipients, particularly known hypersensitivity to penicillin, cephalosporins or other beta-lactam agents and/or allergy to soya or peanut.
2. Lactose or galactose intolerance or glucose-galactose malabsorbtion.
3. Diagnosis criteria of symptomatic neurosyphilis.
4. Pregnant or breastfeeding women.
5. Current treatment with any drugs likely to interact with the study medication (see Appendix 6).
6. Have taken any antibiotics with potential activity against syphilis (e.g. beta lactams, cephalosporines, macrolides, tetracyclines) within 1 week prior to randomization.
7. Uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, bipolar disorder, incapacitating psycho-affective disturbance, acute confusional state.
8. Renal function impairment requiring hemodialysis.
9. Symptomatic concomitant STI (i.e., gonococcus, chlamydia, lymphogranuloma venereum, Mycoplasma genitalium) or other infection disease requiring antibiotic treatment potentially active against syphilis.
10. Having received treatment for the early syphilis recently diagnosed (In the previous 6 months)

Where this trial is running

Barcelona and 5 other locations

• CAP Drassanes-Hospital Universitari Vall d'Hebron — Barcelona, Spain (Recruiting)
• Barcelona Checkpoint — Barcelona, Spain (Recruiting)
• Hospital Clínic de Barcelona — Barcelona, Spain (Recruiting)
• Hospital Germans Trias Pujol — Barcelona, Spain (Recruiting)
• Hospital 12 de Octubre — Madrid, Spain (Recruiting)
• Mortimer Market Centre — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Oriol Mitjà Villar, PhD — Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Study coordinator: Oriol Mitjà Villar, PhD

Conditions Early Latent Syphilis; Primary Syphilis; Secondary Syphilis; Syphilis; Benzathine penicillin G; RPR; Treponema pallidum; Linezolid