Oral Alternative Antibiotics for Patients with Syphilis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

7 Oct 2021 → 20 Mar 2026

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

European Research Council (grant agreement ID: 850450) · Fundació Lluita contra la Sida i les Malalties Infecciones · Instituto de Salud Carlos III

External identifiers

EU CT number

2024-514984-24-00

EudraCT number

2020-005604-19

ClinicalTrials.gov

NCT05069974

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate the non-inferiority of LZD treatment compared with standard BPG treatment to cure patients with early syphilis.

Secondary objectives 4

1. To isolate T.p. strains in clinical samples to subtype DNA from patients at baseline and during recurrence or treatment failure (complements Objective 1).
2. To identify mutations in penicillin-binding proteins that could be linked to a possible penicillin resistance phenotype in case of recurrence or treatment failure (complements Objective 1).
3. To assess the safety of LZD treatment compared with standard BPG treatment in patients with early syphilis.
4. To assess RPR titer variation within 2 weeks after treatment start of primary syphilis.

Conditions and MedDRA coding

Syphilis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Aged 18 years or older at baseline visit.
2. Primary, secondary or early latent syphilis diagnosis based on SEIMC/IUSTI Guidelines*. a. 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. b. Secondary syphilis is defined based on typical clinical symptoms with positive treponemal and non-treponemal tests. c. 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 will be 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 of contraception (abstinence, hormonal contraception, intra-uterine device [IUD], or anatomical sterility in self or partner) in female partner committed during 1 week after last IMP administration.

Exclusion criteria 10

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
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Measurement of clinical cure by the healing of primary syphilis lesions within 2 weeks and secondary syphilis lesions within 6 weeks (clinical cure) from treatment start.
2. Assessment of serological cure by four-fold decline in RPR titer or seroreversion at 12, 24, and 48 weeks (serological cure) from treatment start.
3. Assessment of recurrence by molecular methods of Treponema pallidum (T.p.) DNA to determine relapse or reinfection (molecular cure) within 48 weeks from treatment start.

Secondary endpoints 9

1. Assessment of T.p. strains by genomic molecular methods in ulcer or mucosal lesion swabs from patients with primary or secondary syphilis
2. Assessment of T.p. strains by genomic molecular methods in plasma from patients with secondary or early latent syphilis.
3. Assessment of T.p. strains by genomic molecular methods in oral swab/saliva from patients with secondary or early latent syphilis.
4. Assessment of T.p. strains by genomic molecular methods in skin punch biopsy from patients with secondary syphilis (in a selected group of patients
5. Assessment of T.p. strains by genomic molecular methods in ear lobe scraping from patients with early latent syphilis (in a selected group of patients).
6. Assessment of T.p. strains by genomic molecular methods in CSF from patients with suspicion of neurosyphilis (in a selected group of patients, if lumbar puncture clinically indicated).
7. Comparative genomics between the “resistant” and sensitive T.p. strains to identify mutations that might be the resistance phenotype
8. Proportion of patients with adverse events (AEs) related to LZD treatment compared with standard BPG treatment in patients with early syphilis
9. Change of RPR titer at week 2 from treatment start.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

Sponsor organisation

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

Address

Carretera Canyet S/n

City

Badalona

Postcode

08916

Country

Spain

Scientific contact point

Organisation

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

Contact name

Oriol Mitjà

Public contact point

Organisation

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

Contact name

Oriol Mitjà

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications