Efficacy and Tolerability of Topical LFX453 for External Genital Warts

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02482428
• Collaborator: (none)
• Enrollment: 88
• Location: 1
• Arms: 5
• Actual Duration (Months): 12.6
• Patients Per Site Per Month: 7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
External Genital Warts	Drug: Investigational Treatment; Drug: Aldara	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Vehicle Controlled, Active Comparator, Parallel Group Study to Evaluate Efficacy, Safety, and Tolerability of Topical LFX453 Formulations in Patients With External Genital Warts (EGWs)
• Actual Study Start Date: May 12, 2015
• Actual Primary Completion Date: May 31, 2016
• Actual Study Completion Date: May 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LFX453 0.1% NMC LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	Drug: Investigational Treatment; Applied twice daily for up to 12 weeks
Experimental: LLFX453 0.15% LCC LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Drug: Investigational Treatment; Applied twice daily for up to 12 weeks
Placebo Comparator: Vehicle to NMC Vehicle to nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	Drug: Investigational Treatment; Applied twice daily for up to 12 weeks
Placebo Comparator: Vehicle to LCC Vehicle to liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Drug: Investigational Treatment; Applied twice daily for up to 12 weeks
Active Comparator: Aldara Aldara 5% cream 3 applications per week for a maximum of 16 weeks	Drug: Aldara; Applied 3 times a week for 16 weeks; Other Names: imiquimod

Outcome Measures

Primary Outcome Measures

1. Complete Clearance of Disease at Week 14 [Week 14]

   Number of participants achieving complete clearance of genital warts at Week 14

2. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Arlington Heights	Illinois	United States	60005

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02482428
• Other Study ID Numbers: CLFX453X2202
• First Posted: Jun 26, 2015
• Last Update Posted: Jan 5, 2021
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: human papilloma virus (HPV), Genital Warts, Sexually transmitted disease (STD), viral disease
• Additional relevant MeSH terms: Warts; Condylomata Acuminata; Imiquimod

Study Results

Participant Flow

Recruitment Details	A total of 88 patients were randomized and treated in the study

Arm/Group Title	LFX453 0.1% NMC	LFX453 0.15% LCC	Vehicle to NMC	Vehicle to LCC	Aldara
Arm/Group Description	LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Vehicle to nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	Vehicle to liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Aldara 5% cream 3 applications per week for a maximum of 16 weeks
Period Title: Overall Study
STARTED	24	22	10	10	22
COMPLETED	15	10	9	8	15
NOT COMPLETED	9	12	1	2	7

Baseline Characteristics

Arm/Group Title	LFX453 0.1% NMC	LFX453 0.15% LCC	Vehicle to NMC	Vehicle to LCC	Aldara	Total
Arm/Group Description	LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Vehicle to nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	Vehicle to liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Aldara 5% cream 3 applications per week for a maximum of 16 weeks	Total of all reporting groups
Overall Participants	24	22	10	10	22	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.2 (10.15)	33.3 (9.31)	35.2 (6.75)	38.1 (9.62)	36.0 (9.59)	35.3 (9.31)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	24 100%	22 100%	10 100%	10 100%	22 100%	88 100%

Outcome Measures

1. Primary Outcome

Title	Complete Clearance of Disease at Week 14
Description	Number of participants achieving complete clearance of genital warts at Week 14
Time Frame	Week 14

Outcome Measure Data

Analysis Population Description

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/Group Title	LFX453 0.1% NMC	LFX453 0.15% LCC	Combined Vehicle	Aldara
Arm/Group Description	LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Vehicle to nanomedicinal cream (NMC) and Vehicle to liquid crystal cream (LCC) Twice daily applications	Aldara 5% cream 3 applications per week for a maximum of 16 weeks
Measure Participants	15	10	17	16
Number [participants]	1 4.2%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LFX453 0.1% NMC, Combined Vehicle
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	p value is provided
Statistical Test of Hypothesis	p-Value	0.862
	Comments
	Method	Posterior mean
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 90%; -0.03 to 0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LFX453 0.15% LCC, Combined Vehicle
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	p value is provided
Statistical Test of Hypothesis	p-Value	0.541
	Comments
	Method	posterior mean
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 90%; -0.07 to 0.19
	Parameter Dispersion	Type: Standard Deviation; Value: 0.07
	Estimation Comments

2. Primary Outcome

Title	Number of Adverse Events (AE)/Serious Adverse Events (SAE) as a Measure of Safety and Tolerability up to 30 Weeks
Description	Number of participants with at least one AE/SAE in the category up to 30 weeks
Time Frame	30 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis set included all patients that received any study drug. For Safety & Tolerability only the 2 vehicles have separate analysis.

Arm/Group Title	LFX453 0.1% NMC	LFX453 0.15% LCC	Vehicle to NMC	Vehicle to LCC	Aldara
Arm/Group Description	LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Vehicle to nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	Vehicle to liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Aldara 5% cream 3 applications per week for a maximum of 16 weeks
Measure Participants	24	22	10	10	22
Adverse Events (AEs)	3 12.5%	5 22.7%	3 30%	2 20%	10 45.5%
Serious Adverse Events (SAEs)	0 0%	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	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
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
Time Frame	End of Treatment (EOT) Week 12 or Week 16

Outcome Measure Data

Analysis Population Description

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/Group Title	LFX453 0.1% NMC	LFX453 0.15% LCC	Combined Vehicle	Aldara
Arm/Group Description	LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks	LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks	Vehicle to nanomedicinal cream (NMC) and Vehicle to liquid crystal cream (LCC) Twice daily applications	Aldara 5% cream 3 applications per week for a maximum of 16 weeks
Measure Participants	16	10	17	14
Number [participants]	2 8.3%	1 4.5%	0 0%	3 30%

Adverse Events

Time Frame	Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Arm/Group Title	LFX453 0.1% NMC		LFX453 0.15% LCC		Vehicle to NMC		Vehicle to LCC		Aldara
Arm/Group Description	LFX453 0.1% nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks		LFX453 0.15% liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks		Vehicle to nanomedicinal cream (NMC) Twice daily applications for a maximum of 12 weeks		Vehicle to liquid crystal cream (LCC) Twice daily applications for a maximum of 12 weeks		Aldara 5% cream 3 applications per week for a maximum of 16 weeks
All Cause Mortality
	LFX453 0.1% NMC		LFX453 0.15% LCC		Vehicle to NMC		Vehicle to LCC		Aldara
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LFX453 0.1% NMC		LFX453 0.15% LCC		Vehicle to NMC		Vehicle to LCC		Aldara
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	LFX453 0.1% NMC		LFX453 0.15% LCC		Vehicle to NMC		Vehicle to LCC		Aldara
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)		5/22 (22.7%)		3/10 (30%)		2/10 (20%)		10/22 (45.5%)
Blood and lymphatic system disorders
LEUKOCYTOSIS	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
LEUKOPENIA	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
Gastrointestinal disorders
COELIAC DISEASE	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
NAUSEA	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
General disorders
APPLICATION SITE ERYTHEMA	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		2/22 (9.1%)
APPLICATION SITE PAIN	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
APPLICATION SITE PRURITUS	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
Infections and infestations
NASOPHARYNGITIS	0/24 (0%)		1/22 (4.5%)		1/10 (10%)		0/10 (0%)		1/22 (4.5%)
SINUSITIS	0/24 (0%)		0/22 (0%)		0/10 (0%)		1/10 (10%)		0/22 (0%)
TINEA CRURIS	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
UPPER RESPIRATORY TRACT INFECTION	2/24 (8.3%)		1/22 (4.5%)		1/10 (10%)		0/10 (0%)		0/22 (0%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	0/24 (0%)		0/22 (0%)		0/10 (0%)		1/10 (10%)		0/22 (0%)
AMYLASE INCREASED	0/24 (0%)		1/22 (4.5%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
ASPARTATE AMINOTRANSFERASE INCREASED	0/24 (0%)		0/22 (0%)		0/10 (0%)		1/10 (10%)		0/22 (0%)
BLOOD CREATININE INCREASED	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
CARDIAC MURMUR	0/24 (0%)		1/22 (4.5%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED	0/24 (0%)		0/22 (0%)		0/10 (0%)		1/10 (10%)		0/22 (0%)
HAEMOGLOBIN URINE	0/24 (0%)		0/22 (0%)		0/10 (0%)		1/10 (10%)		0/22 (0%)
LIPASE INCREASED	0/24 (0%)		1/22 (4.5%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
Nervous system disorders
DIZZINESS	0/24 (0%)		0/22 (0%)		1/10 (10%)		0/10 (0%)		0/22 (0%)
HEADACHE	0/24 (0%)		0/22 (0%)		1/10 (10%)		0/10 (0%)		0/22 (0%)
SINUS HEADACHE	0/24 (0%)		0/22 (0%)		0/10 (0%)		1/10 (10%)		0/22 (0%)
SYNCOPE	0/24 (0%)		1/22 (4.5%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
Psychiatric disorders
SLEEP DISORDER DUE TO GENERAL MEDICAL CONDITION, INSOMNIA TYPE	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
Renal and urinary disorders
GLYCOSURIA	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
HAEMATURIA	0/24 (0%)		1/22 (4.5%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
Reproductive system and breast disorders
GENITAL RASH	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		2/22 (9.1%)
PRURITUS GENITAL	1/24 (4.2%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
SCROTAL ERYTHEMA	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		2/22 (9.1%)
SCROTAL ULCER	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
EPISTAXIS	0/24 (0%)		1/22 (4.5%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
WHEEZING	1/24 (4.2%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		0/22 (0%)
Skin and subcutaneous tissue disorders
NIGHT SWEATS	0/24 (0%)		0/22 (0%)		0/10 (0%)		0/10 (0%)		1/22 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.