A Randomized, Placebo-controlled, Double-blind Pilot Study of Single-dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa Loa Infection
- 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.
- DEC is the standard treatment for Loa loa infection, but it can cause mild side effects in persons with low numbers of parasites in their blood, including itchiness, muscle or joint pains, or swelling of the face or limbs. Currently, there is no way to effectively prevent these 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 helps prevent the increase of eosinophils in the blood. Giving reslizumab before DEC treatment might prevent the eosinophils from increasing and thereby might reduce some of the side effects from DEC.
- To determine whether reslizumab can prevent or reduce the side effects of treatment with DEC for Loa loa infestation.
- To evaluate the effect of reslizumab as part of the treatment for Loa loa infestation.
- Individuals between 18 and 65 years of age who have lived in or traveled to a loa-endemic region for at least 1 month. (Loa-endemic regions include northern Angola, Cameroon, Central African Republic, People s Republic of Congo, Equatorial Guinea, Gabon, Nigeria, and the Democratic Republic of Congo.)
- Participants must have low numbers of parasites in the blood, as determined by the screening part of the study.
- 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized, Placebo-controlled, Double-Blind Pilot Study of Single-Dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa Loa Infection|
- Reduction in peak eosinophil count measure as a percent of baseline count. [ Time Frame: during the first 7 days of DEC treatment ] [ Designated as safety issue: No ]
- Frequency and severity of AE's [ Time Frame: all ] [ Designated as safety issue: Yes ]
- Markers of eosinophil activation including levels of eosinophil surface marker expression and serum levels of eosinophil granule proteins [ Time Frame: 12/31/16 ] [ Designated as safety issue: No ]
- Proportion of subjects who clear blood microfilariae [ Time Frame: 3, 7, and 28 days after initiation of treatment with DEC ] [ Designated as safety issue: No ]
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||May 2017|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|Active Comparator: Reslizumab||
Placebo Comparator: Placebo
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111305
|Contact: Nicole C Holland-Thomas, R.N.||(301) firstname.lastname@example.org|
|Contact: Amy D Klion, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Amy D Klion, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|