A Phase 3 interventional study of Linezolid 600 mg (post-interim) and Benzathine Penicilllin G (post-interim) in Early Latent Syphilis, Primary Syphilis and Secondary Syphilis, sponsored by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia. Completed at 11 sites in 2 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-07-29.
Sponsored by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia · Phase 3, Interventional, and Treatment
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.
The syphilis epidemic is rampant around the world, and therapeutic options are restricted to an antibiotic, intramuscular (IM) benzathine penicillin G (BPG), which does not efficiently cross the blood-brain barrier. Treponema pallidum (T.p.), the bacteria that causes syphilis, invades the central nervous system (CNS) in 40% of patients, usually without symptoms. The prognostic implications of CNS invasion are the potential for severe neurologic complications, and treatment failure due to sequestered bacteria in the CNS. When indicated, the only way to identify and treat neurosyphilis is by lumbar puncture to examine the cerebrospinal fluid (CSF), followed by intravenous (IV) Benzyl penicillin therapy. The invetigators have carried out in silico studies showing that oxazolidinones are potentially active against T.p., are neuropenetrative and can be administered orally. The invetigators have carried out preclinical studies using an in vitro culture system for T.p. and the use of the syphilis animal model with rabbits to test different antibiotics. The invetigators have confirmed that LZD was the best compound that could go on to be tested in clinical trials to treat syphilis.
The Trep-AB clinical trial will test the non-inferiority of an investigational neuropenetrative drug, LZD, compared to standard treatment BPG, for early syphilis in humans conducting a randomized controlled clinical.
Primary objective is to demonstrate the non-inferiority of LZD treatment compared with standard BPG treatment to cure patients with early syphilis. Seconday objective is to isolate T.p. strains in clinical samples to subtype DNA from patients at baseline and during recurrence or treatment failure.
PROTOCOL HISTORY
05 Oct 2021 - Initial registration. The Trep-AB master protocol was registered as a two-arm, open-label, randomised non-inferiority trial comparing linezolid 600 mg once daily for 5 days with BPG for early syphilis. The planned recruitment target was 360 participants (180 per treatment group).
Oct 2022 - Prespecified interim analysis. After 59 participants had been enrolled in the pre-interim phase, recruitment to the linezolid 600 mg once-daily for 5 days regimen was discontinued because the prespecified futility criterion was met.
02 Feb 2023 - Major protocol amendment.
Registry update following the amendment. When the registry was updated to reflect the major protocol amendment, the optimised linezolid regimen was added to the existing record without clearly indicating that it replaced the discontinued regimen. Consequently, the registry could be interpreted as describing a three-arm study comprising BPG and both linezolid regimens, although no three-arm comparison was conducted. Similarly, the registered total sample size of 224 represented the 59 participants enrolled during the pre-interim phase plus the planned 165 participants for the post-interim phase; it was not the target sample size for a single three-arm or pooled comparison.
17 Oct 2023 - Added UK participation and additional recruiting sites.
2024-2025 - Subsequent amendments addressed sdministrative and operational aspects of the study without changing the primary endpoint or statistical framework.
Current registry record. The registry has been updated to clarify the sequential structure of the trial. The pre-interim phase evaluated linezolid 600 mg once daily for 5 days and was discontinued for futility; the post-interim phase evaluated linezolid 600 mg twice daily for 10 days in newly randomised participants. The present report concerns the post-interim phase only. The two phases were not concurrent, and participants from the pre-interim phase are not included in the primary efficacy analysis reported here.
126 studies on the registry are indexed under Syphilis; 34 are open to participants now.
This study's enrollment of 165 is below the median of 354 across 85 interventional studies indexed under Syphilis.
Browse Syphilis studies →Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia is the lead sponsor of 45 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Primary, secondary or early latent syphilis diagnosis based on SEIMC/IUSTI Guidelines*
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.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
After randomized to the experimental arm, the patient will take 1 tablet of Linezolid every 12hours during 10 days.
Drug: Linezolid 600 mg (post-interim)
After randomized to the control arm, the patient will receive a single dose of 2.4MUI intramuscular BPG.
Drug: Benzathine Penicilllin G (post-interim)
Linezolid 600mg every 12hours during 10 days
Single dose of intramuscular BPG 2.4 MUI
Proportion of participants achieving overall treatment success
Overall treatment success was defined as achievement of all outcome components applicable to the participant: clinical cure, serological cure, and absence of molecularly confirmed relapse.
Time frame: at week 48
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.
Time frame: 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.
Time frame: at week 6
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.
Time frame: at week 48
Proportion of patients with allelic variation in T. pallidum strain(s) DNA in recurrent syphilis or suspected treatment failure (absence of relapse).
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) in ulcer or mucosa lesions swabs, plasma, or oral swabs.
Time frame: From date of randomization until date of first documented recurrence or treatment failure, assesed up to 48 weeks
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.
Time frame: 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.
Time frame: at week 24
Proportion of patients with antibiotic resistance genotype.
Assesment of allelic variation in core genes conferring antimicrobial resistance in clinical specimens from patients who are considered to have treatment failure compared to patients with adequate clinical and serological response.
Time frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of participants experiencing adverse events.
Assesment of adverse events related to LZD treatment compared with adverse events related to standard BPG treatment in participants with early syphilis.
Time frame: up to 12 weeks
Proportion of patients who have a change in the RPR titer within 2 weeks after treatment start of primary syphilis.
Assessment of RPR titer variation at week 2 from treatment start of patients with primary syphilis.
Time frame: at 2 weeks
Ran from Oct 2021 to primary completion in Apr 2026, 54 months.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Linezolid
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia