Trial Outcomes & Findings for Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama (NCT NCT01790659)

Last Updated: 2018-02-14

Results Overview

The primary efficacy endpoint is percent of subjects with final clinical cure. Final clinical cure is defined as follows: * Subject has initial clinical cure (100% re-epithelialization of index lesion by nominal Day 63); OR, * Subject has initial clinical improvement (\> 50% re-epithelialization of index lesion by nominal Day 63) followed by 100% re-epithelialization of the index lesion on or before nominal Day 100; AND, * Subject has no relapse of index lesion.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

399 participants

Primary outcome timeframe

baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days

Results posted on

2018-02-14

Participant Flow

Subjects were recruited from three regions in Panama. Subjects were screened over a 28 day period.

Participant milestones

Participant milestones
Measure	WR 279,396 (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin Paromomycin alone Paromomycin: Paromomycin alone
Overall Study STARTED	201	198
Overall Study COMPLETED	195	192
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	WR 279,396 n=201 Participants (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=198 Participants Paromomycin alone Paromomycin: Paromomycin alone	Total n=399 Participants Total of all reporting groups
Age, Categorical <=18 years	96 Participants n=5 Participants	88 Participants n=7 Participants	184 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	105 Participants n=5 Participants	110 Participants n=7 Participants	215 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	22.9 years STANDARD_DEVIATION 16.8 • n=5 Participants	23.6 years STANDARD_DEVIATION 15.1 • n=7 Participants	23.2 years STANDARD_DEVIATION 16.0 • n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants	73 Participants n=7 Participants	149 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	125 Participants n=7 Participants	250 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	201 Participants n=5 Participants	196 Participants n=7 Participants	397 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	198 Participants n=5 Participants	192 Participants n=7 Participants	390 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Number of baseline lesions	2.27 Lesions STANDARD_DEVIATION 1.71 • n=5 Participants	2.13 Lesions STANDARD_DEVIATION 1.63 • n=7 Participants	2.20 Lesions STANDARD_DEVIATION 1.67 • n=5 Participants
Lesion sizes	120 mm STANDARD_DEVIATION 146 • n=5 Participants	121 mm STANDARD_DEVIATION 152 • n=7 Participants	120 mm STANDARD_DEVIATION 149 • n=5 Participants
Length of time between initial presence current lesions and treatment	59.7 Days STANDARD_DEVIATION 53.6 • n=5 Participants	62.1 Days STANDARD_DEVIATION 57.7 • n=7 Participants	60.9 Days STANDARD_DEVIATION 55.6 • n=5 Participants

PRIMARY outcome

Timeframe: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days

Population: MITT subjects

Outcome measures

Outcome measures
Measure	WR 279,396 n=201 Participants (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=198 Participants Paromomycin alone Paromomycin: Paromomycin alone
Percent of Participants With Final Clinical Cure	78.6 percent of participants	77.8 percent of participants

SECONDARY outcome

Timeframe: 100 ± 14 days

Population: MITT subjects

• Percentage of subjects with all lesions cured, defined as: Final clinical cure as defined in primary objective (which is based solely on the index lesion); AND, Cure of all other lesions by nominal Day 100 (100% re-epithelialization of all ulcerated lesions and resolution of all other types of lesions)

Outcome measures

Outcome measures
Measure	WR 279,396 n=201 Participants (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=198 Participants Paromomycin alone Paromomycin: Paromomycin alone
Percentage of Subjects With All Lesions Cured	75.1 percentage of participants	76.3 percentage of participants

SECONDARY outcome

Timeframe: Day 168

Population: Cure rates of all lesions over time without regard to subject for mITT subjects

Percentage of all lesions meeting criteria for clinical cure during the study at 168 day mark for mITT subjects

Outcome measures

Outcome measures
Measure	WR 279,396 n=201 Participants (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=198 Participants Paromomycin alone Paromomycin: Paromomycin alone
Percentage of All Lesions Cured at Day 168 (Ignores Per Subject Cure Rate)	77.2 percentage of lesions	83.3 percentage of lesions

SECONDARY outcome

Timeframe: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days

Population: mITT subjects

Area of ulceration (mm\^2) of the index lesion at each measurement time point for mITT subjects

Outcome measures

Outcome measures
Measure	WR 279,396 n=201 Participants (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=198 Participants Paromomycin alone Paromomycin: Paromomycin alone
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Change from baseline Day 100	-144 mm^2 Standard Deviation 163	-152 mm^2 Standard Deviation 165
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Day 168	13.3 mm^2 Standard Deviation 111	1.37 mm^2 Standard Deviation 9.89
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Change from baseline Day 168	-147 mm^2 Standard Deviation 171	-160 mm^2 Standard Deviation 161
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Day 1	153 mm^2 Standard Deviation 137	165 mm^2 Standard Deviation 167
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Day 20	831 mm^2 Standard Deviation 627	928 mm^2 Standard Deviation 986
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Change from baseline Day 20	677 mm^2 Standard Deviation 602	762 mm^2 Standard Deviation 933
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Day 35	68.3 mm^2 Standard Deviation 138	96.1 mm^2 Standard Deviation 188
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Change from baseline Day 35	-84.1 mm^2 Standard Deviation 156	-69.9 mm^2 Standard Deviation 172
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Day 49	29.4 mm^2 Standard Deviation 87.2	33.9 mm^2 Standard Deviation 100
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Change from baseline Day 49	-123 mm^2 Standard Deviation 144	-132 mm^2 Standard Deviation 157
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Day 63	29.9 mm^2 Standard Deviation 119	27.6 mm^2 Standard Deviation 107
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Change from baseline Day 63	-123 mm^2 Standard Deviation 167	-136 mm^2 Standard Deviation 171
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point Day 100	12.5 mm^2 Standard Deviation 85.9	7.41 mm^2 Standard Deviation 56.9

SECONDARY outcome

Timeframe: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days

Population: All lesions for mITT Subjects

Area of ulceration (mm\^2) of all treated lesions from baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days for mITT subjects. Data presented is as presented in the Final Clinical Study Report; any inconsistencies can't be changed.

Outcome measures

Outcome measures
Measure	WR 279,396 n=457 Number of lesions (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=422 Number of lesions Paromomycin alone Paromomycin: Paromomycin alone
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Day 1	115 mm^2 Standard Deviation 152	115 mm^2 Standard Deviation 149
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Day 20	656 mm^2 Standard Deviation 683	699 mm^2 Standard Deviation 897
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Change from baseline Day 35	-62.8 mm^2 Standard Deviation 167	-51.9 mm^2 Standard Deviation 146
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Day 49	21.4 mm^2 Standard Deviation 76.8	23.9 mm^2 Standard Deviation 88.2
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Change from baseline Day 20	533 mm^2 Standard Deviation 632	577 mm^2 Standard Deviation 829
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Day 35	53.0 mm^2 Standard Deviation 132	66.1 mm^2 Standard Deviation 159
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Change from baseline Day 49	-93.8 mm^2 Standard Deviation 160	-92.1 mm^2 Standard Deviation 132
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Day 63	19.9 mm^2 Standard Deviation 94.6	15.8 mm^2 Standard Deviation 82.3
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Change from baseline Day 63	-96.2 mm^2 Standard Deviation 170	-98.7 mm^2 Standard Deviation 142
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Day 100	7.49 mm^2 Standard Deviation 58.8	4.64 mm^2 Standard Deviation 42.8
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Change from baseline Day 100	-113 mm^2 Standard Deviation 166	-109 mm^2 Standard Deviation 143
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Day 168	9.14 mm^2 Standard Deviation 87.7	0.83 mm^2 Standard Deviation 7.23
Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point Change from baseline Day 168	-118 mm^2 Standard Deviation 182	-114 mm^2 Standard Deviation 147

SECONDARY outcome

Timeframe: When 100% re-epithelialization of the index lesion is observed at any visit Study Days (20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days

Population: MITT subjects

Median time to initial clinical cure for index lesions (100% re-epithelialization of the index lesion)

Outcome measures

Outcome measures
Measure	WR 279,396 n=201 Participants (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=198 Participants Paromomycin alone Paromomycin: Paromomycin alone
Median Time to Initial Clinical Cure for Index Lesions	36.000 Days Interval 35.0 to 49.0	48.000 Days Interval 36.0 to 49.0

Adverse Events

WR 279,396

Serious events: 2 serious events

Other events: 201 other events

Deaths: 0 deaths

Paromomycin

Serious events: 1 serious events

Other events: 198 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	WR 279,396 n=201 participants at risk (Paromomycin and Gentamicin Topical Cream) WR 279,396: WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%	Paromomycin n=198 participants at risk Paromomycin alone Paromomycin: Paromomycin alone
Injury, poisoning and procedural complications Second degree burn: scalding water	0.50% 1/201 • Number of events 1 • AE's were assessed at baseline, days 2-9 daily, day 20, 35, 49, 63, 100, and 168 (applicable) AE's including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE.	0.00% 0/198 • AE's were assessed at baseline, days 2-9 daily, day 20, 35, 49, 63, 100, and 168 (applicable) AE's including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE.
Surgical and medical procedures Appendectomy	0.00% 0/201 • AE's were assessed at baseline, days 2-9 daily, day 20, 35, 49, 63, 100, and 168 (applicable) AE's including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE.	0.51% 1/198 • Number of events 1 • AE's were assessed at baseline, days 2-9 daily, day 20, 35, 49, 63, 100, and 168 (applicable) AE's including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE.
Infections and infestations Infection of surgical site	0.00% 0/201 • AE's were assessed at baseline, days 2-9 daily, day 20, 35, 49, 63, 100, and 168 (applicable) AE's including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE.	0.51% 1/198 • Number of events 1 • AE's were assessed at baseline, days 2-9 daily, day 20, 35, 49, 63, 100, and 168 (applicable) AE's including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE.

Other adverse events

Additional Information

Nestor Sosa, MD, FACP

Instituto Conmemorativo Gorgas de Estudios de la Salud

Phone: 507-527-4950

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place