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Trial registered on ANZCTR


Registration number
ACTRN12625000210471
Ethics application status
Approved
Date submitted
20/12/2024
Date registered
21/02/2025
Date last updated
21/02/2025
Date data sharing statement initially provided
21/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
SCIP III: Clinical evaluation of a single, high dose subcutaneous infusion of benzathine penicillin G (SCIP) for treatment of syphilis
Scientific title
SCIP III: Clinical evaluation of a single, high dose subcutaneous infusion of benzathine penicillin G for treatment of syphilis in adults
Secondary ID [1] 313433 0
None
Universal Trial Number (UTN)
U1111-1308-5926
Trial acronym
SCIP III
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Syphilis 335810 0
Condition category
Condition code
Infection 332385 332385 0 0
Sexually transmitted infections
Infection 332386 332386 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
7.2MU (13.8mL) of benzathine penicillin G as Bicillin® L-A given as a single subcutaneous infusion (0.5-1mL/min over 10-30minutes) administered by trained clinicians to adults with non-central nervous system syphilis infections. As this is a one-off treatment, monitoring of participant adherence is not required.
Intervention code [1] 329995 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339939 0
Safety and tolerability including serious adverse events or reactions related to 7.2MU Bicillin® L-A given by subcutaneous infusion resulting in the need for parenteral analgesia, surgical intervention or study withdrawal
Timepoint [1] 339939 0
Adverse events will be assessed from time of infusion and each follow up at day 1, 2, 3, 7, 14 and weeks 6, 12 and 24 post infusion.
Secondary outcome [1] 441990 0
Proportion of patients with penicillin concentrations above the target concentration (0.018mg/mL) for T. pallidum following 7.2MU Bicillin® L-A via subcutaneous infusion at 42 days following administration.
Timepoint [1] 441990 0
Plasma penicillin concentrations will be collected during clinical appointments, the first is immediately pre-infusion and the second is at week 6 post infusion.
Secondary outcome [2] 441991 0
Proportion of patients requiring re-treatment within 6 months for syphilis following 7.2MUBicillin® L-A.
Timepoint [2] 441991 0
Treponemal serology (specific and non-specific) will be performed on day of treatment (day 0) and weeks 12 and 24 post infusion.
Secondary outcome [3] 441995 0
Proportion of patients with measurable serological response (4-fold decrease in RPR titre) following 7.2MU Bicillin® L-A administered by subcutaneous infusion at 6 months
Timepoint [3] 441995 0
Non-specific treponemal serology (RPR) will occur at 12 and 24 weeks post infusion.

Eligibility
Key inclusion criteria
1. Males and non-pregnant females aged 18 years and older (confirmed by negative HCG test)
2. Diagnosis of syphilis infection (made by a clinician) AND requiring treatment with BPG in the form of Bicillin® L-A. This is defined as follows:
a. Positive treponemal serology (Total antibody AND TPPA)
b. Primary syphilis (diagnosed clinically) with PCR confirmation of T. pallidum
3. Contact of an individual with a diagnosis of syphilis infection, requiring empirical treatment with BPG in the form of Bicillin® L-A.
4. Participants who are considered likely to adhere to the trial guidelines for the duration of the trial and are willing and deemed reliable to attend follow up appointments as outlined in the protocol.
5. Able to provide informed consent in accordance with Good Clinical Practice.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or breastfeeding females.
2. Diagnosis of neurosyphilis (CNS, otic or optic syphilis) made by a medical practitioner
3. Known hypersensitivity or contraindication to use of penicillin.
4. History of anaphylactic reaction to cephalosporin antibiotics.
5. Existing dermatological conditions or other abnormalities (e.g., extensive scarring) that may affect skin integrity at the site of injection, especially abdomen or lateral hips.
6. Existing circumstances which are likely to impact patient’s participation in the study, as determined by the research clinician. This may include clinical conditions (i.e., surgery), out of study catchment area, not reliably contactable.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
A pragmatic sample size of 35 participants is chosen to allow for demonstration of tolerability and safety in a target patient population with non-CNS syphilis infection. Assuming that 95% of dosed participants will have penicillin concentrations >18ng/mL at 42 days (expected based on prior pharmacokinetic study in healthy adults), a sample size of at least 33 will estimate the expected proportion (of participants with penicillin concentrations >18ng/mL at 42 days) with 7.5% absolute precision and 95% confidence.

NONMEM compiler will be used for pharmacokinetic analysis. Given the sparse pharmacokinetic sampling planned, the observed concentrations will be assessed with respect to population pharmacokinetic model derived from a previous study of SC administration in healthy volunteers.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/03/2025
Actual
Date of last participant enrolment
Anticipated
3/02/2026
Actual
Date of last data collection
Anticipated
3/08/2026
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 317869 0
Government body
Name [1] 317869 0
Department of Health Sexually Transmitted Infections and Blood Borne Viruses
Country [1] 317869 0
Australia
Primary sponsor type
Other
Name
The Kids Research Institute Australia
Address
Country
Australia
Secondary sponsor category [1] 320207 0
None
Name [1] 320207 0
Address [1] 320207 0
Country [1] 320207 0
Other collaborator category [1] 283318 0
Other
Name [1] 283318 0
M Clinic, WAAC
Address [1] 283318 0
Country [1] 283318 0
Australia
Other collaborator category [2] 283319 0
University
Name [2] 283319 0
The University of Western Australia
Address [2] 283319 0
Country [2] 283319 0
Australia
Other collaborator category [3] 283320 0
University
Name [3] 283320 0
Curtin University
Address [3] 283320 0
Country [3] 283320 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316548 0
The University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 316548 0
http://www.research.uwa.edu.au/staff/human-research/welcome-to-HREO
Ethics committee country [1] 316548 0
Australia
Date submitted for ethics approval [1] 316548 0
09/09/2024
Approval date [1] 316548 0
19/11/2024
Ethics approval number [1] 316548 0
2024/ET000591

Summary
Brief summary
Syphilis is an important public health threat in Australia. Benzathine penicillin G (BPG) is the current treatment of choice of non-CNS syphilis infection. Primary, secondary or early latent syphilis is treated with 2.4 million units (MU) of intramuscular BPG injections, while late latent syphilis requires 2.4MU weekly for 3 consecutive weeks. IM BPG injections are associated with significant pain and discomfort for recipients. Consequently, treatment uptake is low, especially where multiple doses are required.

Subcutaneous (SC) delivery of BPG is potentially a more efficacious alternative to the current IM injection. Our team has demonstrated acceptability and a superior pharmacokinetic profile in healthy volunteers. Additionally, a small cohort of patients with syphilis reported SC delivery of BPG as a preferred alternative.

This study aims to further demonstrate safety and tolerability of a single 7.2MU dose of BPG given as a subcutaneous infusion for the treatment of syphilis. Secondary objectives include demonstrating efficacy of 7.2MU BPG as subcutaneous infusion for the treatment of syphilis and to estimate the proportion of patients with penicillin concentrations above the target concentration of 18mg/mL. Primary outcome is the assessment of safety and tolerability including serious adverse events and reactions. Secondary outcomes are the change in nontreponemal specific serology at 6 months, plasma penicillin concentrations at 6 weeks and the proportion of participants with treatment failure requiring re-treatment at 6 months.

We aim to recruit 35 patients with confirmed syphilis infection or contacts of confirmed syphilis infection who would require empirical treatment, at the M Clinic. This study will incorporate self-guided online surveys exploring participant experiences receiving subcutaneous infusion of BPG for syphilis treatment. Participants will be followed up for 24 weeks from day of treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 138234 0
A/Prof Laurens Manning
Address 138234 0
The University of Western Australia (M582), 35 Stirling Highway, Crawley, WA 6009, Australia
Country 138234 0
Australia
Phone 138234 0
+61 8 6151 1156
Fax 138234 0
Email 138234 0
[email protected]
Contact person for public queries
Name 138235 0
Thel Hla
Address 138235 0
Perth Children's Hospital 15 Hospital Ave, Nedlands Western Australia 6009
Country 138235 0
Australia
Phone 138235 0
+61421832230
Fax 138235 0
Email 138235 0
[email protected]
Contact person for scientific queries
Name 138236 0
Thel Hla
Address 138236 0
Perth Children's Hospital 15 Hospital Ave, Nedlands Western Australia 6009
Country 138236 0
Australia
Phone 138236 0
+61421832230
Fax 138236 0
Email 138236 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.