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

NCT03637660 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 17-0101
• Study Type: interventional
• Target: 249
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Syphilis

Keywords

Benzathine penicillin G; Early Syphillis; HIV; Phase 4

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With a Serological Response by Month 6.

  Serological response to therapy by Month 6 was defined as follows, where available rapid plasma reagin (RPR) results from all visits prior to the end of the Month 6 visit window (i.e., scheduled visits up to and including the Month 6 visit, early termination visit, or any unscheduled visit that occurred prior to the end of month 6 visit window) were evaluated: * 4-fold or greater decline in RPR titer at any visit prior to the end of the Month 6 visit window compared to baseline, OR * RPR-negative at any visit prior to the end of the Month 6 visit window (i.e., seroreversion).

  Day 1 to Day 180

Secondary Outcomes (25)

• Categorical Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire

  Day 1

• Continuous Descriptive Statistics of Sexual History at Baseline Collected Via a Study-specific Questionnaire

  Day 1

• Categorical Descriptive Statistics of Socio-epidemiologic Characteristics at Baseline Collected Via a Study-specific Questionnaire

  Day 1

• Continuous Descriptive Statistics of Socio-epidemiologic Characterictics at Baseline Collected Via a Study-specific Questionnaire

  Day 1

• Categorical Descriptive Statistics of Participant Baseline Demographics Collected Via a Study-specific Questionnaire

  Day 1

Study Arms (2)

1

ACTIVE COMPARATOR

2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly on Day 1, n=280

Drug: Benzathine Penicillin

2

EXPERIMENTAL

2.4 million units (MU) of Benzathine penicillin G (BPG) intramuscularly weekly for three successive weeks, n=280

Drug: Benzathine Penicillin

Interventions

Benzathine Penicillin DRUG

BPG will be administered as a deep intramuscular injection in the upper, outer quadrant of the buttock.

1; 2

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is aged 18 years or older.
• Subject has provided informed consent.
• 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.
• 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).
• If subject is of childbearing potential, subject has a negative urine or serum pregnancy test.
• Subject is willing to have an human immunodeficiency virus (HIV) test, participate in HIV counseling, and return to clinic for follow-up.
• 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.
• 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

You may not qualify if:

• Subject previously enrolled in this trial.
• 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
• Subject has a known or suspected allergy or hypersensitivity to penicillin or other beta-lactam antibiotics.
• Subject has a known or suspected sexually transmitted infection (STI) other than syphilis requiring treatment with a drug active against T. pallidum.
• 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.
• Subject has suspected or known ongoing drug use that might interfere with study participation and follow-up treatment.
• Subject is breastfeeding.
• 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.
• Subject has any other condition that, in the opinion of the investigator, would interfere with participation in the study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (10)

University of Alabama at Birmingham School of Medicine - Infectious Disease

Birmingham, Alabama, 35294, United States

Location

Emory University Hospital Midtown - Emory Clinic Infectious Diseases

Atlanta, Georgia, 30308, United States

Location

Indiana University School of Medicine - Infectious Diseases

Indianapolis, Indiana, 46202, United States

Location

Louisiana State University Health Sciences Center

New Orleans, Louisiana, 70119, United States

Location

Johns Hopkins Bayview Medical Center - Infectious Diseases

Baltimore, Maryland, 21224, United States

Location

Fenway Health - The Fenway Institute

Boston, Massachusetts, 02115, United States

Location

University of North Carolina School of Medicine - Center for Infectious Diseases

Durham, North Carolina, 27701-3720, United States

Location

Wake Forest Baptist Health - Infectious Diseases

Winston-Salem, North Carolina, 27157, United States

Location

Magee Women's Hospital of UPMC - Reproductive Infectious Disease Research

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Washington - Harborview Medical Center - Center for AIDS and STD

Seattle, Washington, 98104-2433, United States

Location

Related Publications (4)

• Hook EW 3rd, Dionne JA, Workowski K, McNeil CJ, Taylor SN, Batteiger TA, Dombrowski JC, Mayer KH, Sena AC, Hamill MM, Wiesenfeld HC, Zhu C, Perlowski C, Mejia-Galvis JE, Newman LM. One Dose versus Three Doses of Benzathine Penicillin G in Early Syphilis. N Engl J Med. 2025 Sep 4;393(9):869-878. doi: 10.1056/NEJMoa2401802.

  PMID: 40902161 DERIVED

• Dionne JA, Zhu C, Mejia-Galvis J, Workowski K, Batteiger TA, Dombrowski JC, Mayer KH, McNeil CJ, Sena AC, Taylor S, Wiesenfeld HC, Hamill MM, Perlowski C, Hook EW 3rd. Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment in Adults With Early Syphilis: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Feb 3;8(2):e2459490. doi: 10.1001/jamanetworkopen.2024.59490.

  PMID: 39946129 DERIVED

• Dionne JA, Giacani L, Tamhane A, Workowski K, Lieberman NAP, Greninger AL, Perlowski C, Newman L, Hook EW 3rd. Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis. J Infect Dis. 2024 Jun 14;229(6):1628-1636. doi: 10.1093/infdis/jiad582.

  PMID: 38124508 DERIVED

• Dionne-Odom J, Workowski K, Perlowski C, Taylor SN, Mayer KH, McNeil CJ, Hamill MM, Dombrowski JC, Batteiger TA, Sena AC, Wiesenfeld HC, Newman L, Hook EW 3rd. Coinfection With Chlamydial and Gonorrheal Infection Among US Adults With Early Syphilis. Sex Transm Dis. 2022 Aug 1;49(8):e87-e89. doi: 10.1097/OLQ.0000000000001605. Epub 2022 Jan 24.

  PMID: 35067599 DERIVED

MeSH Terms

Conditions

Syphilis

Interventions

Penicillin G Benzathine

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Edward W. Hook, III
• Organization: University of Alabama at Birmingham

ehooks@uabmc.edu

205-932-4204

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2018
• First Posted: August 20, 2018
• Study Start: October 31, 2018
• Primary Completion: September 7, 2022
• Study Completion: March 20, 2023
• Last Updated: January 14, 2025
• Results First Posted: December 26, 2023

Record last verified: 2019-09-19

Locations

US (10)