A randomized non-inferiority clinical trial of doxycycline vs BPG for early syphilis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

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

6 Dec 2021 → 23 Jul 2025

Decision date (initial)

2024-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513532-23-00

EudraCT number

2019-003278-21

ClinicalTrials.gov

NCT04838717

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The main objective of our study is to show that 100 mg doxycycline bid for 14 days is non-inferior to a single intramuscular injection of 2.4 x 106 IU of BPG for the treatment of early syphilis, evaluated as a four-fold decrease in titer in the non-treponemal assay (VDRL or RPR) at month 6 (widely used as the definition of cure in real-life settings).

Secondary objectives 4

1. To evaluate the tolerance of the two regimens in terms of severe adverse events (SAEs)
2. To evaluate adherence to the doxycycline regimen
3. To evaluate the impact of the two regimens on other sexually transmitted diseases at month 6
4. To demonstrate that doxycycline is non-inferior to a single intramuscular injection of BPG in titer in the non-treponemal assay (VDRL or RPR) at month 3

Conditions and MedDRA coding

early syphilis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients aged ≥ 18 years
2. Patients who, after the nature of the study has been explained to them, and before any protocol-specific procedures are performed, give informed consent in writing, in accordance with local regulatory requirements
3. Patients with or without HIV infection and with syphilis infection in the early stages according to CDC criteria (primary syphilis, secondary syphilis and early latent syphilis of less than one year’s duration)
4. Patients with a positive non-treponemal assay result
5. Patients available for participation and follow-up during the 6 months of the study
6. Patients covered by the French health insurance system

Exclusion criteria 13

1. Individuals with a history of known hypersensitivity to doxycycline or any other antibiotic of the tetracycline family, BPG (hypersensitivity to the active substance benzathine benzylpenicillin, to other penicillins, to soy phospholipids, peanuts or any of the excipients in the product ; history of severe immediate hypersensitivity reactions (eg anaphylaxis) to other beta-lactams (examples: cephalosporins, carbapenemes or monobactams), lidocaïne (hypersensitivity to lidocaine hydrochloride, amide-linked local anesthetics, or any of the excipients listed in SPC) and / or any of the excipients of the specialties used in the study
2. Patients with a negative non-treponemal assay result
3. Patients receiving an anticoagulant therapy
4. Individuals with contraindications for either of the study drugs
5. Individuals treated with retinoids by general route
6. Individuals with early and late neurosyphilis
7. Individuals requiring doxycycline treatment
8. Individuals with late syphilis, whether or not latent (e.g. cutaneous)
9. Individuals with thrombocytopenia or coagulation disorders contraindicating intramuscular injections
10. Women who are pregnant or breast-feeding, or of childbearing age not using or planning to use acceptable birth control measures
11. Individuals under a measure of legal protection or unable to consent
12. Individuals participating in any clinical trial with another investigational product in the 28 days preceding the first study visit or intending to participate in another clinical study at any time during the course of this study.
13. Recent exposure (within the last three months) to either of the two study drugs

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A response will be defined as a four-fold decrease (2 dilutions) in titer in the non-treponemal assay (VDRL or RPR) at month 6 relative to the results of the assay performed before treatment. The two assays (before treatment and at month 6) should be performed in the same laboratory

Secondary endpoints 4

1. Occurrence of SAEs in the two groups
2. Adherence to doxycycline, evaluated on the basis of a tablet count between weeks 1 and 2, during planned visits
3. Occurrence of other STDs in the two groups at month 6
4. Titer obtained in the non-treponemal assay (VDRL or RPR) at month 3 evolution

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nicolas DUPIN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nicolas DUPIN

Locations

1 EU/EEA country · 21 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 7 files

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

Application history

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