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Phase 4 Comparative Trial of Benzathine Penicillin G for Treatment of Early Syphilis in Subjects With or Without HIV Infection

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ClinicalTrials.gov Identifier: NCT03637660
Recruitment Status : Recruiting
First Posted : August 20, 2018
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a single injected dose of 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 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.

Condition or disease Intervention/treatment Phase
Syphilis Drug: Benzathine Penicillin Phase 4

Detailed Description:
This is a phase 4, randomized, open-label, multicenter trial to evaluate the efficacy of a single injected dose of 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 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. The secondary objectives are: 1) to determine if the difference in response to therapy between treatment arms by Month 6 differs among subjects with or without HIV infection; 2) to determine the impact of multiple BPG injected doses on subject compliance with study product and adherence to the corresponding scheduled visits; 3) to determine the incidence and manifestations of the Jarisch-Herxheimer reaction among subjects treated for early syphilis with BPG; 4) to collect prospective data up to Month 12 on the serological response to therapy in subjects treated for early syphilis with either BPG regimen; 5) to compare epidemiological characteristics of early syphilis among subjects with or without HIV infection.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 560 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 4 Comparative Trial of Benzathine Penicillin G 2.4 Million Units Administered as a Single Dose Versus Three Successive Weekly Doses for Treatment of Early Syphilis in Subjects With or Without HIV Infection
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : March 1, 2022
Estimated Study Completion Date : March 1, 2022


Arm Intervention/treatment
Active Comparator: 1
2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly on Day 1, n=280
Drug: Benzathine Penicillin
BPG will be administered as a deep intramuscular injection in the upper, outer quadrant of the buttock.

Experimental: 2
2.4 million units(MU) of Benzathine penicillin G (BPG) intramuscularly weekly for three successive weeks, n=280
Drug: Benzathine Penicillin
BPG will be administered as a deep intramuscular injection in the upper, outer quadrant of the buttock.




Primary Outcome Measures :
  1. The proportion of subjects with a serological response (defined as either a 4-fold or greater decline in rapid plasma reagin (RPR) titer compared to baseline or being rapid plasma reagin-negative [seroreversion]) [ Time Frame: Month 6 ]

Secondary Outcome Measures :
  1. Descriptive statistics of sexual history at baseline collected via a study-specific questionnaire [ Time Frame: Day 1 ]
  2. Descriptive statistics of socio-epidemiologic characteristics at baseline collected via a study-specific questionnaire [ Time Frame: Day 1 ]
  3. Descriptive statistics of subject baseline demographics collected via a study-specific questionnaire [ Time Frame: Day 1 ]
  4. Descriptive statistics of subject sexual history by HIV status collected via a study-specific questionnaire [ Time Frame: Through Month 12 ]
  5. The proportion of subjects who receive all assigned doses within the protocol-specified visit windows [ Time Frame: Through Month 12 ]
  6. The proportion of subjects who report Jarisch-Herxheimer reaction manifestations (including fever, intensification of rash, myalgia, and other systemic symptoms) [ Time Frame: Day 1 through Day 2 ]
  7. The proportion of subjects with a serological response (defined as either a 4-fold or greater decline in rapid plasma reagin (RPR) titer compared to baseline or being rapid plasma reagin-negative [seroreversion]) [ Time Frame: Month 12 ]
  8. The proportion of subjects with a serological response (defined as either a 4-fold or greater decline in rapid plasma reagin (RPR) titer compared to baseline or being rapid plasma reagin-negative [seroreversion]) summarized by HIV status [ Time Frame: Month 12 ]
  9. The proportion of subjects with a serological response (defined as either a 4-fold or greater decline in rapid plasma reagin (RPR) titer compared to baseline or being rapid plasma reagin-negative [seroreversion]) summarized by HIV status [ Time Frame: Month 6 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 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 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.
  9. Subject has any other condition that, in the opinion of the investigator, would interfere with participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03637660


Contacts
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Contact: Edward Watson Hook 12059344202 ehook@uab.edu

Locations
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United States, Alabama
University of Alabama at Birmingham School of Medicine- Infectious Disease Recruiting
Birmingham, Alabama, United States, 35294
United States, Georgia
Emory University Hospital Midtown - Emory Clinic Infectious Diseases Recruiting
Atlanta, Georgia, United States, 30308
United States, Indiana
Indiana University School of Medicine - Infectious Diseases Recruiting
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Louisiana State University Health Sciences Center Recruiting
New Orleans, Louisiana, United States, 70119
United States, Maryland
Johns Hopkins Bayview Medical Center - Infectious Diseases Recruiting
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Fenway Health - The Fenway Institute Recruiting
Boston, Massachusetts, United States, 02115
United States, North Carolina
University of North Carolina School of Medicine - Center for Infectious Diseases Recruiting
Durham, North Carolina, United States, 27701-3720
Wake Forest Baptist Health - Infectious Diseases Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
Magee Women's Hospital of UPMC - Reproductive Infectious Disease Research Recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington - Harborview Medical Center - Center for AIDS and STD Recruiting
Seattle, Washington, United States, 98104-2433
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03637660    
Other Study ID Numbers: 17-0101
HHSN272201300012I
First Posted: August 20, 2018    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: September 19, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Benzathine penicillin G
Early Syphillis
HIV
Phase 4
Additional relevant MeSH terms:
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Syphilis
HIV Infections
Infection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Treponemal Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Sexually Transmitted Diseases, Bacterial
Spirochaetales Infections
Genital Diseases, Male
Genital Diseases, Female
Penicillins
Penicillin G
Penicillin G Benzathine
Penicillin G Procaine
Anti-Bacterial Agents
Anti-Infective Agents