Reslizumab to Prevent Post-treatment Eosinophilia in Loiasis

Phase 2

Completed

Conditions: Loiasis

Interventions: Drug: Reslizumab
Drug: Diethylcarbamazine
Other: Placebo

Registration Number: NCT01111305

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: Diethylcarbamazine citrate (DEC) treatment of Loa loa infection is complicated by the development of severe adverse reactions that are correlated with the number of circulating microfilariae in the blood. The cause of these reactions is unknown, but they are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation. This randomized, placebo-controlled, double-blind pilot study (conducted at the NIH Clinical Center) will assess whether and to what extent the administration of reslizumab (Cinquil ), a humanized monoclonal antibody directed against IL-5, given 3 to 7 days before administration of the anthelminthic drug DEC (at 3 mg/kg 3 times daily for 21 days), prevents the development of eosinophilia in 10 adult subjects with Loa loa infection and 0-5000 microfilariae/mL. Secondary outcomes will include the severity of post-treatment effects, markers of eosinophil activation, and effects of reslizumab on microfilarial clearance.

Detailed Description: Background:

Loa loa is a parasitic worm that infects people in West and Central Africa and is spread by the bite of a deerfly. Adult worms (macrofilariae) live under the skin and cause symptoms such as swellings, itching, and hives. Smaller worms (microfilariae) are found in the bloodstream. Diethylcarbamazine (DEC), the recommended medication for Loa loa infection, can produce very serious side effects, especially in people with high numbers of parasites in the blood. Researchers are investigating new treatments for Loa loa that have fewer or less serious side effects. Researchers believe that a certain kind of blood cells called eosinophils, which increase in the blood after DEC treatment, may be one of the causes of the side effects seen with DEC treatment. Reslizumab is a drug that lowers eosinophils in the blood. Giving reslizumab before DEC treatment might prevent the eosinophils from increasing and reduce some of the side effects from DEC.

Objectives:

- To determine whether reslizumab can prevent or reduce the side effects of treatment with DEC for Loa loa infection.

Eligibility:

Screening: Individuals between 18 and 65 years of age who have lived in or traveled to a Loa-endemic region for at least 1 month

Treatment study: Individuals with Loa loa infection and low numbers of parasites in the blood

Design:

This study will last 24 months and will involve several visits to the National Institutes of Health Clinical Center. Participants will be screened with a blood test for Loa loa parasites. Those who have a low number of Loa loa parasites in the blood will be asked to return for a full medical evaluation and the start of the treatment phase. Those who do not have Loa loa parasites in the blood, or those who have a high number of Loa loa parasites in the blood, are not eligible for this study treatment but may be eligible for other parasitic disease studies conducted by the National Institutes of Health.

Participants will have an initial visit with a full physical evaluation, and blood and urine tests (including leukapheresis to provide sufficient numbers of blood cells for testing). Within 1 month of the first visit, participants will have a single infusion of either reslizumab or a placebo. The infusion visit is estimated to last approximately 5 hours. Three to 7 days after the infusion, participants will begin a 21-day course of DEC (taken by mouth) to treat the infection. Participants will stay overnight at the Clinical Center during the first 3 days of treatment with DEC to be monitored for side effects, and will continue to take the DEC at home after the inpatient treatment. A study coordinator will call participants each day to ask about any symptoms or side effects. Participants will be seen for an additional eight outpatient follow-up visits (at days 7, 14, and 28, and months 3, 6, 12, 18, and 24) for evaluation of signs and symptoms of infection.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 31

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + DEC	Placebo	Placebo iv single dose followed by diethylcarbamazine 9 mg/kg/day po for 21 days
Reslizumab + DEC	Reslizumab	Reslizumab 1 mg/kg iv single dose followed by diethylcarbamazine 9 mg/kg/day po for 21 days
Placebo + DEC	Diethylcarbamazine	Placebo iv single dose followed by diethylcarbamazine 9 mg/kg/day po for 21 days
Reslizumab + DEC	Diethylcarbamazine	Reslizumab 1 mg/kg iv single dose followed by diethylcarbamazine 9 mg/kg/day po for 21 days

Primary Outcome Measures

Name	Time	Method
Peak Eosinophil Count Post-treatment	during the first 7 days of DEC treatment	Peak eosinophil count during the first 7 days of treatment as a percent of the baseline count

Secondary Outcome Measures

Name	Time	Method
Markers of Eosinophil Activation	one week	serum eosinophil granule protein levels on day 7 measured as % baseline
Frequency of AE's	7 days following initiation of DEC treatment	Adverse events during the first week of DEC treatment
Proportion of Subjects Who Clear Blood Microfilariae	3, 7, and 28 days after initiation of treatment with DEC