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
This study is currently recruiting participants.
Verified February 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT01111305
First received: April 24, 2010
Last updated: May 14, 2013
Last verified: February 2013
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Purpose
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:
- 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.
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Loiasis |
Drug: Reslizumab Drug: Diethylcarbamazine |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double-Blind 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 |
Resource links provided by NLM:
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
- Reduction in peak eosinophil count measure during the first 7 days of DEC treatment as a percent of baseline count. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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 ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 300 |
| Study Start Date: | April 2010 |
| Estimated Study Completion Date: | May 2017 |
| Estimated Primary Completion Date: | May 2017 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
Drug: Reslizumab
N/A
Drug: Diethylcarbamazine
N/A
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(Trademark)), 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| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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:
- Between 18 and 65 years of age
- 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:
- Known to be pregnant
- 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:
- The subject has documented loiasis with 0-5000 microfilariae/mL blood.
- The subject agrees to storage of samples for study
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:
- The subject tests positive for HIV infection or has any other known immunodeficiency.
- The subject has a concomitant active infection with Onchocerca volvulus.
- The subject has used any other investigational agent within the past 30 days.
- The subject has used immunosuppressive agents (as listed in section 8.1) within the past 30 days.
- The subject has a history of allergic reaction to any antibody therapy or to DEC.
- The subject has chronic kidney or liver disease.
- The subject has any condition that, in the Investigator's opinion, places the subject at undue risk by participating in the study.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111305
Contacts
| Contact: Amy D Klion, M.D. | (301) 435-8903 | aklion@niaid.nih.gov |
Locations
| 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 prpl@mail.cc.nih.gov | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | Amy D Klion, M.D. | National Institute of Allergy and Infectious Diseases (NIAID) |
More Information
Additional Information:
Publications:
| Responsible Party: | National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ) |
| ClinicalTrials.gov Identifier: | NCT01111305 History of Changes |
| Other Study ID Numbers: | 100101, 10-I-0101 |
| Study First Received: | April 24, 2010 |
| Last Updated: | May 14, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
Filariasis Post-Treatment Reactions Monoclonal Antibody Loa Loa Loiasis |
Additional relevant MeSH terms:
|
Spirurida Infections Secernentea Infections Nematode Infections Parasitic Diseases Eosinophilia Loiasis Leukocyte Disorders Hematologic Diseases Filariasis Helminthiasis Antibodies Diethylcarbamazine |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Lipoxygenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Filaricides Antinematodal Agents Anthelmintics Antiparasitic Agents Anti-Infective Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013