Miltefosine to Treat Mucocutaneous Leishmaniasis

NCT01050907 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PBL-MILT-201
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Mucosal Leishmaniasis; Cutaneous Leishmaniasis

Keywords

leishmaniasis; cutaneous disease; mucosal disease; miltefosine

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Clinical Cure of Lesions

  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.

  Week 6, Month 3, Month 7, and Month 13

• Number of Participants With Adverse Events

  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.

  Up to 7 months for CL; Up to 13 months for ML

Study Arms (1)

Miltefosine

EXPERIMENTAL

2.5 mg/kg/day for 28 days

Drug: Miltefosine

Interventions

Miltefosine DRUG

2.5 mg/kg/day for 28 days

Also known as: Impavido

Miltefosine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is the subject a male or female at least 18 years of age?
• Does the subject weigh at least 30 kg?
• 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?
• In the opinion of the investigator, is the subject capable of understanding and complying with the protocol?
• 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?
• Has the patient signed informed consent?

You may not qualify if:

• Is the subject a female who is breast-feeding?
• 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
• 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?

Sponsors & Collaborators

• Knight Therapeutics (USA) Inc: lead

Study Sites (2)

For this treatment IND, each Physician entered patients at his/her own facility. Below data is for protocol central contact:

Bethesda, Maryland, 20852, United States

Location

NIH

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Leishmaniasis, Mucocutaneous; Leishmaniasis, Cutaneous; Leishmaniasis

Interventions

miltefosine

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Jonathan D. Berman
• Organization: Fast-Track Drugs and Biologics, LLC

jberman@fasttrackresearch.com

301-922-2097

Study Officials

• Jonathan Berman, MD

  Fast Track Drugs and Biologics LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 18, 2010
• Study Start: May 1, 2010
• Primary Completion: February 1, 2015
• Study Completion: March 1, 2015
• Last Updated: September 30, 2020
• Results First Posted: September 30, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)