Alternative Antibiotics for Syphilis

NCT05069974 | Active Not Recruiting Phase 3

• 2 other identifiers: Trep-AB2020-005604-19
• Study Type: interventional
• Target: 224
• Locations: 2 countries
• Sites: 6

Brief Summary

The Trep-AB clinical trial will test the efficacy of an investigational neuropenetrative drug, Linezolid (LZD), compared to standard treatment, Benzathine penicillin G (BPG), for early syphilis in humans. The overarching idea of the work proposed herein is to investigate the use of LZD to treat syphilis, conducting a randomized controlled clinical trial to evaluate this new indication of a known antibacterial agent.

Conditions

Early Latent Syphilis; Primary Syphilis; Secondary Syphilis

Keywords

Syphilis; Benzathine penicillin G; RPR; Treponema pallidum; Linezolid

Outcome Measures

Primary Outcomes (6)

• Proportion of patients with clinical resolution of primary syphilis lesions (clinical cure, primary).

  Assesment of clinical resolution defined as the complete healing of primary syphilis lesions within 2 weeks from treatment start.

  at week 2

• Proportion of patients with clinical resolution of secondary syphilis lesions (clinical cure, secondary).

  Assesment of clinical resolution defined as the complete healing of secondary syphilis lesions within 6 weeks from treatment start.

  at week 6

• Proportion of patients with adequate serological response (serological cure, week 12).

  Assessment of adequate serological response defined as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion to negative.

  at week 12

• Proportion of patients with adequate serological response (serological cure, week 24).

  Assessment of adequatesserological response defined as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion to negative.

  at week 24

• Proportion of patients with adequate serological response (serological cure, week 48).

  Assessment of adequate serological response defined as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion to negative.

  at week 48

• Proportion of patients with allelic variation in T. pallidum strain(s) DNA in recurrent syphilis or suspected treatment failure (molecular cure).

  Assessment of re-infection in recurrent syphilis as defined by allelic variation in core genes of T. pallidum strain(s) compared to baseline using a molecular method (MLST-WGS).

  From date of randomization until date of first documented recurrence or treatment failure, assesed up to 48 weeks

Secondary Outcomes (9)

• Proportion of patients with allelic variation in T. pallidum strain(s) DNA in ulcer or mucosa lesions swabs (re-infection).

  From date of randomization until date of first documented recurrence, assesed up to 48 weeks

• Proportion of patients with allelic variation in T. pallidum strain(s) DNA in plasma (re-infection).

  From date of randomization until date of first documented recurrence, assesed up to 48 weeks

• Proportion of patients with allelic variation in T. pallidum strain(s) DNA in oral swab/saliva (re-infection).

  From date of randomization until date of first documented recurrence, assesed up to 48 weeks

• Proportion of patients with allelic variation in T. pallidum strain(s) DNA in skin punch biopsy (re-infection).

  From date of randomization until date of first documented recurrence, assesed up to 48 weeks

• Proportion of patients with allelic variation in T. pallidum strain(s) DNA in ear lobe scraping (re-infection).

  From date of randomization until date of first documented recurrence, assesed up to 48 weeks

Study Arms (3)

Linezolid (LZD) 1200

EXPERIMENTAL

Patients will take film coated tables of LZD 600 mg every 12 hours during 10 days

Drug: Linezolid 600 mg

Benzathine Penicillin G (BPG)

ACTIVE COMPARATOR

Administration of intramuscular BPG 2.4 MIU single dose during day 1

Drug: Benzathine Penicilllin G

Linezolid (LZD) 600

EXPERIMENTAL

Patients will take film coated tables of LZD 600 mg every 24 hours during 5 days

Drug: Linezolid 600 mg

Interventions

Linezolid 600 mg DRUG

After randomized to the experimental arm, the patient will take 1 tablet of Linezolid every 12hours during 10 days or 1 tablet of of Linezolid every 24hours during 5 days.

Linezolid (LZD) 1200; Linezolid (LZD) 600

Benzathine Penicilllin G DRUG

After randomized to the control arm, the patient will receive a single dose of intramuscular BPG.

Benzathine Penicillin G (BPG)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older at baseline visit.
• Primary, secondary or early latent syphilis diagnosis based on SEIMC/IUSTI Guidelines\*
• 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.
• Secondary syphilis is defined based on typical clinical symptoms with positive treponemal and non-treponemal tests.
• Signature of written informed consent.
• Ability to comply with the requirements of the study protocol.
• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead

Study Sites (6)

CAP Drassanes-Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08001, Spain

Location

Barcelona Checkpoint

Barcelona, Barcelona, 08015, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital Germans Trias Pujol

Barcelona, Barcelona, 08916, Spain

Location

Hospital 12 de Octubre

Madrid, Madrid, Spain

Location

Mortimer Market Centre

London, United Kingdom

Location

Related Publications (1)

• Ubals M, Nadal-Baron P, Arando M, Rivero A, Mendoza A, Descalzo Jorro V, Ouchi D, Perez-Mana C, Alvarez M, Alemany A, Hoyos-Mallecot Y, Nunley E, Lieberman NAP, Greninger AL, Galvan-Casas C, Suner C, G-Beiras C, Paredes R, Rodriguez-Gascon A, Canut A, Garcia-Patos V, Farre M, Marks M, Giacani L, Vall-Mayans M, Mitja O. Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2024 Apr;24(4):404-416. doi: 10.1016/S1473-3099(23)00683-7. Epub 2024 Jan 8.

  PMID: 38211601 DERIVED

MeSH Terms

Conditions

Syphilis, Latent; Syphilis, primary; Syphilis, secondary; Syphilis; Treponemal Infections

Interventions

Linezolid

Condition Hierarchy (Ancestors)

Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Oriol Mitjà Villar, PhD

  Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The statistical analysis will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Open-label, non inferiority, randomized clinical trial. Eligible patients will be randomized to recieve Linezolid (experimental arm) or BPG (control arm).

Study Record Dates

• First Submitted: September 16, 2021
• First Posted: October 6, 2021
• Study Start: October 14, 2021
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: July 22, 2025

Record last verified: 2025-07

Locations

GB (1); ES (5)