External Genital Warts
Conditions
Keywords
human papilloma virus (HPV), Genital Warts, Sexually transmitted disease (STD), viral disease
Brief summary
The LFX453X2202 study tested the investigational drug LFX453 against placebo for safety, tolerability, and efficacy in treating genital warts in circumcised men, in parallel with an additional open label arm using imiquimod 5%. During the study the patients received either LFX453, placebo or active comparator and the tolerability and safety was assessed continuously through local tolerability assessments and adverse event recorded. Efficacy was clinical evaluations and lesion count. During the study biopsies were taken for analysis of pharmacokinetics and biomarkers. Blood samples were taken for safety, pharmacokinetics (PK), and biomarkers.
Interventions
Applied twice daily for up to 12 weeks
DRUGAldara
Applied 3 times a week for 16 weeks
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Circumcised male 18-60 years * Clinical diagnosis of external genital warts * Agree to remain abstinent or to use condoms during intercourse for the duration of the study * Agree to digital photographs of treated area
Exclusion criteria
* Any treatment of genital warts within one month of treatment start * HPV vaccination * presence of warts larger than 200 mm2 * Genital herpes within one month of treatment start * History of Bowenoid papulosis * significant illness within 2 weeks of treatment start * use of other investigational drugs * known hypersensitivity to study drugs or constituents * history of ECG abnormalities * History of significant heart conditions * Impaired renal function * Abnormal liver function * History of immunodeficiency disease * Drug or alcohol abuse * Immunosuppressive therapies * Malignancies in the past 5 years * hypertrophic scarring
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Clearance of Disease at Week 14 | Week 14 | Number of participants achieving complete clearance of genital warts at Week 14 |
| Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | 30 weeks | Number of participants with at least one AE/SAE in the category up to 30 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Had Partial Clearance Rate of at Least 75 Percent Reduction in External Genital Wart (EGW)s Count at End of Treatment (EOT) Week 12 or 16 | End of Treatment (EOT) Week 12 or Week 16 | Number of Participants that had partial clearance rate of at least 75 percent reduction in External Genital Wart (EGW)s count at end of treatment (EOT) Week 12 or 16 |
Countries
United States
Participant flow
Recruitment details
A total of 88 patients were randomized and treated in the study
Participants by arm
| Arm | Count |
|---|---|
| LFX453 0.1% NMC LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks | 24 |
| LFX453 0.15% LCC LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks | 22 |
| Vehicle to NMC Vehicle to nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks | 10 |
| Vehicle to LCC Vehicle to liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks | 10 |
| Aldara Aldara 5% cream 3 applications per week for a maximum of 16 weeks | 22 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 9 | 1 | 2 | 4 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 |
| Overall Study | protocol deviation | 1 | 1 | 0 | 0 | 0 |
| Overall Study | subject/guardian decision | 4 | 2 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | LFX453 0.1% NMC | LFX453 0.15% LCC | Vehicle to NMC | Vehicle to LCC | Aldara | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 10.15 | 33.3 years STANDARD_DEVIATION 9.31 | 35.2 years STANDARD_DEVIATION 6.75 | 38.1 years STANDARD_DEVIATION 9.62 | 36.0 years STANDARD_DEVIATION 9.59 | 35.3 years STANDARD_DEVIATION 9.31 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 22 Participants | 10 Participants | 10 Participants | 22 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 24 | 5 / 22 | 3 / 10 | 2 / 10 | 10 / 22 |
| serious Total, serious adverse events | 0 / 24 | 0 / 22 | 0 / 10 | 0 / 10 | 0 / 22 |
Outcome results
Primary
Complete Clearance of Disease at Week 14
Number of participants achieving complete clearance of genital warts at Week 14
Time frame: Week 14
Population: Pharmacodynamics (PD) data sets included all randomized patients For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LFX453 0.1% NMC | Complete Clearance of Disease at Week 14 | 1 participants |
| LFX453 0.15% LCC | Complete Clearance of Disease at Week 14 | 0 participants |
| Combined Vehicle | Complete Clearance of Disease at Week 14 | 0 participants |
| Aldara | Complete Clearance of Disease at Week 14 | 0 participants |
p-value: 0.86290% CI: [-0.03, 0.2]Posterior mean
p-value: 0.54190% CI: [-0.07, 0.19]posterior mean
Primary
Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks
Number of participants with at least one AE/SAE in the category up to 30 weeks
Time frame: 30 weeks
Population: The safety analysis set included all patients that received any study drug. For Safety \& Tolerability only the 2 vehicles have separate analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LFX453 0.1% NMC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Adverse Events (AEs) | 3 participants |
| LFX453 0.1% NMC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Serious Adverse Events (SAEs) | 0 participants |
| LFX453 0.15% LCC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Adverse Events (AEs) | 5 participants |
| LFX453 0.15% LCC | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Serious Adverse Events (SAEs) | 0 participants |
| Combined Vehicle | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Adverse Events (AEs) | 3 participants |
| Combined Vehicle | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Serious Adverse Events (SAEs) | 0 participants |
| Aldara | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Serious Adverse Events (SAEs) | 0 participants |
| Aldara | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Adverse Events (AEs) | 2 participants |
| Aldara | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Adverse Events (AEs) | 10 participants |
| Aldara | Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks | Serious Adverse Events (SAEs) | 0 participants |
Secondary
Number of Participants That Had Partial Clearance Rate of at Least 75 Percent Reduction in External Genital Wart (EGW)s Count at End of Treatment (EOT) Week 12 or 16
Number of Participants that had partial clearance rate of at least 75 percent reduction in External Genital Wart (EGW)s count at end of treatment (EOT) Week 12 or 16
Time frame: End of Treatment (EOT) Week 12 or Week 16
Population: Pharmacodynamics (PD) data sets included all randomized patients For efficacy end points only there were combined analysis of the 2 vehicle groups. Vehicle groups were analyzed separately for safety and tolerability only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LFX453 0.1% NMC | Number of Participants That Had Partial Clearance Rate of at Least 75 Percent Reduction in External Genital Wart (EGW)s Count at End of Treatment (EOT) Week 12 or 16 | 2 participants |
| LFX453 0.15% LCC | Number of Participants That Had Partial Clearance Rate of at Least 75 Percent Reduction in External Genital Wart (EGW)s Count at End of Treatment (EOT) Week 12 or 16 | 1 participants |
| Combined Vehicle | Number of Participants That Had Partial Clearance Rate of at Least 75 Percent Reduction in External Genital Wart (EGW)s Count at End of Treatment (EOT) Week 12 or 16 | 0 participants |
| Aldara | Number of Participants That Had Partial Clearance Rate of at Least 75 Percent Reduction in External Genital Wart (EGW)s Count at End of Treatment (EOT) Week 12 or 16 | 3 participants |