Phase 4 Comparative Trial of Benzathine Penicillin G for Treatment of Early Syphilis in Subjects With or Without HIV Infection
Condition: Syphilis
MeSH terms: HIV Infections; Syphilis
Intervention: Benzathine Penicillin
Intervention description: BPG will be administered as a deep intramuscular injection in the upper, outer quadrant of the buttock.
Intervention MeSH terms: Penicillins; Penicillin G Benzathine; Penicillin G; Penicillin G Procaine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 249.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Benzathine penicillin G; Early Syphillis; HIV; Phase 4

Summary:

      This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a
      single injected dose of Benzathine Penicillin G (BPG) 2.4 MU (Arm 1) compared to three
      successive weekly injected doses of BPG 2.4 MU (Arm 2) for treatment of early syphilis in
      human immunodeficiency virus (HIV)-infected and HIV-uninfected subjects. The study will
      enroll 560 adults (to achieve 420 evaluable subjects) aged 18 years or older with untreated
      early syphilis (primary, secondary, or early latent). It will be conducted at 9 sites in the
      US and last for 48 months with patient participation duration of 12 months. The primary
      objective is to compare the serological response to therapy in subjects with early (primary,
      secondary, or early latent) syphilis treated with Benzathine Penicillin G (BPG) 2.4 million
      units (MU) once or weekly for three successive weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is aged 18 years or older.

          2. Subject has provided informed consent.

          3. Subject has untreated primary*, secondary**, or early latent*** syphilis.

             *Primary syphilis is characterized by the presence of an ulcerative lesion at a
             potential site of inoculation (while classically solitary, shallow, painless and with
             an indurated, clean base, primary lesions may be multiple, may vary considerably in
             appearance, and/or may not be painless) or by darkfield, acceptable polymerase chain
             reaction (PCR), or direct fluorescence antibody-T. pallidum (DFA-TP) positive ulcers.

             **Secondary syphilis is characterized by classical palmar/plantar rash, condylomata
             lata, mucous patches, etc. or by darkfield, acceptable PCR, or DFA-TP positive
             lesions.

             ***Early latent syphilis is characterized by current reactive serologic tests for
             syphilis (STS) and a documented non-reactive STS, or documented sexual exposure to an
             individual known to have primary, secondary, or early latent syphilis diagnosed within
             the last 12 months.

          4. Subject either has a newly reactive non-treponemal test (such as an RPR test) or a
             history of syphilis and a current increase in RPR titer of two or more dilutions
             (i.e., four-fold).

          5. If subject is of childbearing potential, subject has a negative urine or serum
             pregnancy test.

          6. Subject is willing to have an human immunodeficiency virus (HIV) test, participate in
             HIV counseling, and return to clinic for follow-up.

          7. In the opinion of the investigator, subject is able and willing to comply with study
             procedures, including receipt of three Benzathine Penicillin G (BPG) injected doses if
             randomized to Arm 2.

          8. If female, subject must be of non-childbearing potential* or must be using an
             acceptable method of birth control** to avoid becoming pregnant.

               -  Non-childbearing potential is defined as being post-menopausal for at least 1
                  year, status after bilateral tubal ligation, or status after bilateral
                  oophorectomy, or status after hysterectomy.

                    -  Subject must agree to avoid becoming pregnant by using one of the following
                       acceptable methods of birth control for the entire duration of participation
                       in the trial:

                         -  Intrauterine contraceptive device; OR

                         -  Oral contraceptives; OR

                         -  Hormonal injections; OR

                         -  Hormonal implants; OR

                         -  Contraceptive patches; OR

                         -  Monogamous relationship with vasectomized partner; OR

                         -  Exclusively same-sex relationships; OR

                         -  Use of condoms by the male partner; OR

                         -  Abstinence

        Exclusion Criteria:

          1. Subject previously enrolled in this trial.

          2. Subject has latent syphilis of unknown duration, late latent syphilis, or evidence of
             neurosyphilis, including ocular syphilis.*

             *e.g., eye pain/redness, recent ocular change, and/or changes in visual acuity

          3. Subject has a known or suspected allergy or hypersensitivity to penicillin or other
             beta-lactam antibiotics.

          4. Subject has a known or suspected sexually transmitted infection (STI) other than
             syphilis requiring treatment with a drug active against T. pallidum.

          5. Subject has used antibiotics* active against T. pallidum in the preceding 30 days.

             *Note: the use of antimicrobials known to NOT be effective against T. pallidum (e.g.,
             quinolones, sulfonamides, trimethoprim, metronidazole, spectinomycin) will be allowed.

          6. Subject has suspected or known ongoing drug use that might interfere with study
             participation and follow-up treatment.

          7. Subject is breastfeeding.

          8. Subject has used an investigational drug in the past 30 days that might interfere with
             safety or efficacy assessment.

             *If the subject has used any investigational drugs in the past 30 days, contact the
             Principal Investigator, Division of Microbiology and Infectious Diseases (DMID)
             Clinical Project Manager, DMID Medical Officer, and FHI 360 to confirm eligibility.

          9. Subject has any other condition that, in the opinion of the investigator, would
             interfere with participation in the study.