Miltefosine to Treat Mucocutaneous Leishmaniasis

• Sponsor: Knight Therapeutics (USA) Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01050907
• Collaborator: (none)
• Enrollment: 4
• Locations: 2
• Arm: 1
• Duration (Months): 58
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this Treatment Investigational New Drug application was to make miltefosine available for mucocutaneous leishmaniasis patients presenting in the United States.

If entrance criteria were met, subjects with mucosal or cutaneous leishmaniasis received miltefosine at a targeted dose of 2.5 mg/kg/day for 28 days. During treatment at weeks 1, 2, and 4, the patient returned to the treatment facility to be assessed for adverse events. Blood for transaminase and creatinine values were drawn at the midpoint and at the end of therapy.

Patients returned to the treatment facility to be examined clinically at 6 weeks (ie, 2 weeks after the end of therapy), 3 months (2 months after therapy), and 7 months (6 months after treatment) for mucosal leishmaniasis and cutaneous leishmaniasis patients, and also at 13 months (12 months after treatment) for mucosal leishmaniasis patients.

Condition or Disease	Intervention/Treatment	Phase
Mucosal Leishmaniasis; Cutaneous Leishmaniasis	Drug: Miltefosine	Phase 2

Detailed Description

Subjects with mucosal leishmaniasis or cutaneous leishmaniasis from which Leishmania have already been identified were potentially eligible to be treated with miltefosine via this protocol. Treating Physicians with potentially eligible subjects contacted the protocol Principal Investigator (PI), and received the case report forms (CRF) from the PI. The Treating Physician completed the screening CRF pages for demographics, medical history, leishmaniasis history, clinical laboratory results that were available, and identification of Leishmania in the lesion, and sent the completed CRF pages to the PI. If after PI review, the subject was potentially eligible for the protocol, the PI sent the protocol, the miltefosine package insert, the informed consent form, and a blank copy of FDA form 1572 to the Treating Physician. Although this protocol would have already been approved by a "central" Institutional Review Board (IRB), if there was an additional need to have the Treating Physician's local IRB approve the protocol, the Treating Physician would obtain the approval, and obtain informed consent from the subject. The rest of the laboratory tests were accomplished so that all screening laboratory tests were completed prior to enrolling a potential subject. If in the physician's opinion the subject appeared eligible for enrollment, the Treating Physician sent to the PI the local IRB signature page (if needed), protocol signature page, informed consent signed by both the subject and the Treating Physician, the rest of the completed CRF pages for screening, and the form 1572 completed with the Treating Physician's information plus the Treating Physician's curriculum vitae. After the PI's review of these forms, the investigational product was sent from the drug repository to the Treating Physician for that subject's use.

Treatment was daily for 28 consecutive days. During treatment at weeks 1, 2, and 4, the subject returned to the treatment facility to be assessed for adverse events and to receive additional supply of medication if needed. Compliance with drug administration was assessed by subject interview and pill count. Blood for transaminase and creatinine values were drawn at the midpoint and at the end of therapy.

Subjects returned to the treatment facility to be examined clinically at Study Week 6, Study Months 3 and 7 months for mucosal leishmaniasis and cutaneous leishmaniasis subjects, and also at Study Month 13 for mucosal leishmaniasis subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Mucocutaneous Leishmaniasis With Miltefosine
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Miltefosine 2.5 mg/kg/day for 28 days	Drug: Miltefosine; 2.5 mg/kg/day for 28 days; Other Names: Impavido

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Cure of Lesions [Week 6, Month 3, Month 7, and Month 13]

   Percent of participants with clinical cure of all lesions. Ulcerated CL lesions were measured for the longest diameter and perpendicular width of ulceration; non-ulcerated lesions were measured for length and width of the raised area. A healed lesion was 100% reduction in lesion area (0x0); a cured lesion was a lesion healed at the Month 7 visit. For subjects with ML, an Ear, Nose, and Throat specialist examined the nasal and oral mucosa. Each site (nasal skin, nasal mucosa, palate, pharynx, larynx) was evaluated for signs of disease (erythema, edema, infiltration, erosion) and graded on a scale: 0=no disease, 1=mild disease, 2=moderate disease, 3=severe disease. Max score was 60 = poor outcome. Clinical response measured as a composite score, the mucosal severity score, which was the sum of the severity scores for each clinical sign at each clinical site of disease. A healed lesion had a score of 0 in absolute value (0% of the entrance score), and clinical cure was lesion is healed.

2. Number of Participants With Adverse Events [Up to 7 months for CL; Up to 13 months for ML]

   The number of participants with adverse events (AEs) by occurrence and severity. The Treating Physician monitored participants for the occurrence of AEs from the time the first investigational product was taken on Day 1 through the end of follow up at Month 7 for CL or Month 13 for ML. For the period between Study Day 1 and Study Week 6 (2 weeks after the end of therapy), all AEs regardless of seriousness or relationship to the investigational product were to be recorded on the case report form (CRF). For the period Week 6 to Month 7 for CL, or Month 13 for ML, only AEs requiring medical attention were recorded on the CRF.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Is the subject a male or female at least 18 years of age?

2. Does the subject weigh at least 30 kg?

3. Does the subject have a diagnosis of mucosal leishmaniasis or cutaneous leishmaniasis in at least one lesion by at least one of the following methods: 1) positive culture for promastigotes of lesion material, 2) microscopic identification of amastigotes in stained lesion tissue, 3) Polymerase chain reaction of lesion material?

4. In the opinion of the investigator, is the subject capable of understanding and complying with the protocol?

5. If female and of child-bearing potential, did the subject have a negative pregnancy test during screening and agree to use an acceptable method of birth control during the treatment phase and for 6 months after treatment is completed?

6. Has the patient signed informed consent?

Exclusion Criteria:

1. Is the subject a female who is breast-feeding?

2. Does the subject have a clinically significant medical disorder?

• Thrombocyte count <100 x 10e9/L

• Leukocyte count <3 x 10e9/L

• Haemoglobin <10 g/100 mL

• Aspartate transaminiase (ASAT), alanine transaminase (ALAT) >2 times upper limit of normal range

• Bilirubin >1.5 times upper limit of normal range

• Serum creatinine >1.5 times upper limit of normal range

• Major surgery within last 2 weeks

• Any non-compensated or uncontrolled condition

1. In the last 4 weeks up to the present, has the subject received other treatment for leishmaniasis, including any medication with pentavalent antimony; amphotericin B, paromomycin, or imidazoles?

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For this treatment IND, each Physician entered patients at his/her own facility. Below data is for protocol central contact:	Bethesda	Maryland	United States	20852
2	NIH	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• Knight Therapeutics (USA) Inc

Investigators

• Principal Investigator: Jonathan Berman, MD, Fast Track Drugs and Biologics LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 6, 2010

More Information

Publications

None provided.

• Responsible Party: Knight Therapeutics (USA) Inc
• ClinicalTrials.gov Identifier: NCT01050907
• Other Study ID Numbers: PBL-MILT-201
• First Posted: Jan 18, 2010
• Last Update Posted: Sep 30, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Knight Therapeutics (USA) Inc: leishmaniasis; cutaneous disease; mucosal disease; miltefosine
• Additional relevant MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Miltefosine

Study Results

Participant Flow

Arm/Group Title	Miltefosine
Arm/Group Description	Miltefosine: 2.5 mg/kg/day for 28 days
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Miltefosine
Arm/Group Description	Miltefosine: 2.5 mg/kg/day for 28 days
Overall Participants	4
Age (Count of Participants)
<=18 years	1 25%
Between 18 and 65 years	3 75%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 25%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 25%
White	2 50%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Cure of Lesions
Description	Percent of participants with clinical cure of all lesions. Ulcerated CL lesions were measured for the longest diameter and perpendicular width of ulceration; non-ulcerated lesions were measured for length and width of the raised area. A healed lesion was 100% reduction in lesion area (0x0); a cured lesion was a lesion healed at the Month 7 visit. For subjects with ML, an Ear, Nose, and Throat specialist examined the nasal and oral mucosa. Each site (nasal skin, nasal mucosa, palate, pharynx, larynx) was evaluated for signs of disease (erythema, edema, infiltration, erosion) and graded on a scale: 0=no disease, 1=mild disease, 2=moderate disease, 3=severe disease. Max score was 60 = poor outcome. Clinical response measured as a composite score, the mucosal severity score, which was the sum of the severity scores for each clinical sign at each clinical site of disease. A healed lesion had a score of 0 in absolute value (0% of the entrance score), and clinical cure was lesion is healed.
Time Frame	Week 6, Month 3, Month 7, and Month 13

Outcome Measure Data

Analysis Population Description

The evaluable population included all subjects who received daily doses of investigational product for at least 25 of the total of 28 days, had lesion measurements at Month 7 for cutaneous leishmaniasis or the month 13 visit for mucosal leishmaniasis, and who did not receive rescue medications to treat leishmaniasis at any time during the study.

Arm/Group Title	Miltefosine
Arm/Group Description	Miltefosine: 2.5 mg/kg/day for 28 days
Measure Participants	4
Count of Participants [Participants]	3 75%

2. Primary Outcome

Title	Number of Participants With Adverse Events
Description	The number of participants with adverse events (AEs) by occurrence and severity. The Treating Physician monitored participants for the occurrence of AEs from the time the first investigational product was taken on Day 1 through the end of follow up at Month 7 for CL or Month 13 for ML. For the period between Study Day 1 and Study Week 6 (2 weeks after the end of therapy), all AEs regardless of seriousness or relationship to the investigational product were to be recorded on the case report form (CRF). For the period Week 6 to Month 7 for CL, or Month 13 for ML, only AEs requiring medical attention were recorded on the CRF.
Time Frame	Up to 7 months for CL; Up to 13 months for ML

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received any administration of investigational product.

Arm/Group Title	Miltefosine
Arm/Group Description	Miltefosine: 2.5 mg/kg/day for 28 days
Measure Participants	4
Count of Participants [Participants]	4 100%

Adverse Events

Time Frame	Up to 7 months for CL; Up to 13 months for ML
Arm/Group Title	Miltefosine
Arm/Group Description	Miltefosine: 2.5 mg/kg/day for 28 days
All Cause Mortality
	Miltefosine
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Miltefosine
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Miltefosine
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Gastrointestinal disorders
Abdominal Pain Lower	1/4 (25%)	1
Nausea	2/4 (50%)	7
Vomiting	2/4 (50%)	8
Reproductive system and breast disorders
Epididymitis	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Rash Pruritic	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.