Trial Outcomes & Findings for Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World (NCT NCT00703924)

Last Updated: 2017-05-30

Results Overview

CCR is defined as at least 50% reduction, from baseline, in index lesion area of ulceration at study days 50, 100 and 180 (+ 7 days). Randomized subjects were compared using the uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable. The Breslow-Day test was used to examine whether the effect of WR 279,396 varied between subgroups

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

92 participants

Primary outcome timeframe

180 days

Results posted on

2017-05-30

Participant Flow

Participant milestones

Participant milestones
Measure	WR 279,396 WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion
Overall Study STARTED	50	42
Overall Study COMPLETED	49	41
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	WR 279,396 WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	WR 279,396 n=50 Participants WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo n=42 Participants Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion	Total n=92 Participants Total of all reporting groups
Age, Customized <18 years	47 years n=5 Participants	33 years n=7 Participants	80 years n=5 Participants
Age, Customized >18 years	3 years n=5 Participants	9 years n=7 Participants	12 years n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	15 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Region of Enrollment France	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Tunisia	45 participants n=5 Participants	37 participants n=7 Participants	82 participants n=5 Participants

PRIMARY outcome

Timeframe: 180 days

Outcome measures

Outcome measures
Measure	WR 279,396 n=50 Participants WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo n=42 Participants Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion	Day 100 100% Re-epithelialization by day 100	Day 180 (+7 Days) 100% Re-epithelialization by day 180 (+7 days)
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days) CCR	47 Participants	30 Participants	—	—
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days) CCR Failure	3 Participants	12 Participants	—	—

PRIMARY outcome

Timeframe: 180 days

Population: All solicited local and systemic AEs and SAEs including immediate and delayed reactions that occurred during this study are summarized.

Safety was evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations.

Outcome measures

Outcome measures
Measure	WR 279,396 n=50 Participants WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo n=42 Participants Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion	Day 100 100% Re-epithelialization by day 100	Day 180 (+7 Days) 100% Re-epithelialization by day 180 (+7 days)
Safety of WR 279,396 (AEs and SAEs) Solicated AEs- Mild	49 Adverse Events	40 Adverse Events	—	—
Safety of WR 279,396 (AEs and SAEs) Solicited AEs- Moderate	11 Adverse Events	5 Adverse Events	—	—
Safety of WR 279,396 (AEs and SAEs) Solicited AEs- Severe	2 Adverse Events	2 Adverse Events	—	—
Safety of WR 279,396 (AEs and SAEs) Non-Solicited AEs- Mild	13 Adverse Events	20 Adverse Events	—	—
Safety of WR 279,396 (AEs and SAEs) Non-Solicited AEs- Moderate	10 Adverse Events	10 Adverse Events	—	—
Safety of WR 279,396 (AEs and SAEs) Non-Soliciated AEs- Severe	0 Adverse Events	0 Adverse Events	—	—
Safety of WR 279,396 (AEs and SAEs) SAEs	1 Adverse Events	0 Adverse Events	—	—

SECONDARY outcome

Timeframe: 180 days

Population: Days to 100% re-epithelialization of index lesion. Volunteer Identification Number (VIN). VINs 17, 72, and 109 failed to meet 100% re-epithelialization

100% re-epithelialization of the index lesion without having had a relapse. The log-rank test was used to compare the time to complete re-epithelialization.

Outcome measures

Outcome measures
Measure	WR 279,396 n=92 Participants WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo n=92 Participants Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion	Day 100 n=92 Participants 100% Re-epithelialization by day 100	Day 180 (+7 Days) n=92 Participants 100% Re-epithelialization by day 180 (+7 days)
Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse WR 279,396	10 Participants	34 Participants	4 Participants	1 Participants
Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse Placebo	20 Participants	10 Participants	9 Participants	1 Participants

SECONDARY outcome

Timeframe: 180 days

Final cure rate by subject was determined using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.

Outcome measures

Outcome measures
Measure	WR 279,396 n=50 Participants WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo n=42 Participants Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion	Day 100 100% Re-epithelialization by day 100	Day 180 (+7 Days) 100% Re-epithelialization by day 180 (+7 days)
Final Cure Rate by Subject of All Lesions CCR	46 Participants	29 Participants	—	—
Final Cure Rate by Subject of All Lesions Treatment Failure	4 Participants	13 Participants	—	—

SECONDARY outcome

Timeframe: 180 days

Relapse is defined as enlargement of the index lesion compared to previous measurement at any time after day 50 (+ 7 days) or not demonstrating CCR by study day 180. CCR was compared using uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.

Outcome measures

Outcome measures
Measure	WR 279,396 n=50 Participants WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo n=42 Participants Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion	Day 100 100% Re-epithelialization by day 100	Day 180 (+7 Days) 100% Re-epithelialization by day 180 (+7 days)
Rate of Relapse	0 Participants	3 Participants	—	—

Adverse Events

WR 279,396

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	WR 279,396 n=50 participants at risk WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin WR 279,396: A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion	Placebo n=42 participants at risk Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Placebo: Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion
Injury, poisoning and procedural complications Arm fracture	2.0% 1/50 • Number of events 1 • Duration of study (180 days (+7 days) AEs were evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations. * Immediate: observed within 30 minutes of application * Delayed: observed just prior to next application	0.00% 0/42 • Duration of study (180 days (+7 days) AEs were evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations. * Immediate: observed within 30 minutes of application * Delayed: observed just prior to next application

Other adverse events

Additional Information

Afif Ben Salah, MD, PhD

Institute Pasteur Tunisia

Phone: 216-71-792-429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place