Clinical Trial: 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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 I

Brief Summary:

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.
  • 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.

Objectives:

  • 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.

Eligibility:

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

    Current Primary Outcome: Reduction in peak eosinophil count measure as a percent of baseline count. [ Time Frame: during the first 7 days of DEC treatment ]

    Original Primary Outcome: Reduction in peak eosinophil count measure during the first 7 days of DEC treatment as a percent of baseline count. [ Time Frame: 7 days ]

    Current Secondary Outcome:

    • Frequency and severity of AE's [ Time Frame: all ]
    • Markers of eosinophil activation including levels of eosinophil surface marker expression and serum levels of eosinophil granule proteins [ Time Frame: 12/31/16 ]
    • Proportion of subjects who clear blood microfilariae [ Time Frame: 3, 7, and 28 days after initiation of treatment with DEC ]


    Original Secondary Outcome: Frequency and severity of AE's, markers of eosinophil activation proportion of subjects who clear blood microfilariae and time to clearance at 3, 7, and 28 days, rate of recurrence of microfilaremia and/or clinical symptoms. [ Time Frame: 2 years ]

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: April 24, 2010
    Date Started: April 2010
    Date Completion: May 2017
    Last Updated: November 9, 2016
    Last Verified: November 2016