Reslizumab to Prevent Post-treatment Eosinophilia in Loiasis
Condition: Loiasis
MeSH terms: Loiasis; Eosinophilia
Intervention: Reslizumab; Diethylcarbamazine; Placebo
Intervention MeSH terms: Diethylcarbamazine; Reslizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Drug assignment (reslizumab vs. placebo) and eosinophil count
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Filariasis; Post-Treatment Reactions; Monoclonal Antibody; Loa Loa; Loiasis

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA: (Screening)

        A subject will be eligible for participation in the screening portion of this protocol if
        all of the following criteria apply:

          1. Between 18 and 65 years of age

          2. Residence in or travel to a Loa-endemic region for greater than 1 month

        EXCLUSION CRITERIA: (Screening)

        A subject will not be eligible for participation in the screening portion of this study if
        any of the following conditions apply:

          1. Known to be pregnant

          2. Known to be HIV-positive

        INCLUSION CRITERIA: (Interventional Study)

        A subject will be eligible for participation in the interventional portion of the study
        only if all of the following criteria apply:

          1. The subject has documented loiasis with 0-5000 microfilariae/mL blood.

          2. The subject agrees to storage of samples for study

          3. A female subject is eligible for this study if she is any of the following:

               -  Not pregnant or breast-feeding.

               -  Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal
                  ligation or are post-menopausal, as defined by no menses in greater than or equal
                  to 1 year)

               -  Of childbearing potential but agrees to practice effective contraception* or
                  abstinence for 3 months after administration of the investigational study drug
                  (reslizumab or placebo)

                    -  NOTE: Acceptable methods of contraception may include one or more of the
                       following: 1) male partner who is sterile prior to the female subject s
                       entry into the study and is the sole sexual partner for the female subject;
                       2) implants of levonorgestrel; 3) injectable progestogen, an intrauterine
                       device with a documented failure rate of less than 1percent; 4) oral
                       contraceptives; and 5) double barrier methods including diaphragm or condom
                       with a spermicide.

        EXCLUSION CRITERIA: (Interventional Study)

        A subject will not be eligible to participate in the interventional portion of the study if
        any of the following conditions are fulfilled at the time of enrollment:

          1. The subject tests positive for HIV infection or has any other known immunodeficiency.

          2. The subject has a concomitant active infection with Onchocerca volvulus.

          3. The subject has used any other investigational agent within the past 30 days.

          4. The subject has used immunosuppressive agents (as listed in section 8.1) within the
             past 30 days.

          5. The subject has a history of allergic reaction to any antibody therapy or to DEC.

          6. The subject has chronic kidney or liver disease.

          7. The subject has any condition that, in the Investigator s opinion, places the subject
             at undue risk by participating in the study.