Reslizumab to Prevent Post-treatment Eosinophilia in Loiasis
Condition: Loiasis
MeSH terms: Loiasis; Eosinophilia
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Reslizumab; Diethylcarbamazine; Placebo
Intervention type(s): Drug; Drug; Other
Other intervention name(s): Cinqair; Hetrazan, Banocide
Intervention MeSH terms: Diethylcarbamazine; Reslizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Filariasis; Post-Treatment Reactions; Monoclonal Antibody; Loa Loa; Loiasis