Reslizumab to Prevent Post-treatment Eosinophilia in Loiasis

NCT01111305 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 10-I-0101100101
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Loiasis

Keywords

Filariasis; Post-Treatment Reactions; Monoclonal Antibody; Loa Loa; Loiasis

Outcome Measures

Primary Outcomes (1)

• Peak Eosinophil Count Post-treatment

  Peak eosinophil count during the first 7 days of treatment as a percent of the baseline count

  during the first 7 days of DEC treatment

Secondary Outcomes (3)

• Frequency of AE's

  7 days following initiation of DEC treatment

• Markers of Eosinophil Activation

  one week

• Proportion of Subjects Who Clear Blood Microfilariae

  3, 7, and 28 days after initiation of treatment with DEC

Study Arms (2)

Reslizumab + DEC

ACTIVE COMPARATOR

Reslizumab 1 mg/kg iv single dose followed by diethylcarbamazine 9 mg/kg/day po for 21 days

Drug: Reslizumab; Drug: Diethylcarbamazine

Placebo + DEC

PLACEBO COMPARATOR

Placebo iv single dose followed by diethylcarbamazine 9 mg/kg/day po for 21 days

Drug: Diethylcarbamazine; Other: Placebo

Interventions

Reslizumab DRUG

Also known as: Cinqair

Reslizumab + DEC

Diethylcarbamazine DRUG

Also known as: Hetrazan, Banocide

Placebo + DEC; Reslizumab + DEC

Placebo OTHER

Placebo + DEC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Limaye AP, Abrams JS, Silver JE, Ottesen EA, Nutman TB. Regulation of parasite-induced eosinophilia: selectively increased interleukin 5 production in helminth-infected patients. J Exp Med. 1990 Jul 1;172(1):399-402. doi: 10.1084/jem.172.1.399.

  PMID: 2193099 BACKGROUND

• Klion AD, Massougbodji A, Sadeler BC, Ottesen EA, Nutman TB. Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. J Infect Dis. 1991 Jun;163(6):1318-25. doi: 10.1093/infdis/163.6.1318.

  PMID: 2037798 BACKGROUND

• Klion AD, Ottesen EA, Nutman TB. Effectiveness of diethylcarbamazine in treating loiasis acquired by expatriate visitors to endemic regions: long-term follow-up. J Infect Dis. 1994 Mar;169(3):604-10. doi: 10.1093/infdis/169.3.604.

  PMID: 8158033 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Loiasis; Filariasis

Interventions

reslizumab; Diethylcarbamazine

Condition Hierarchy (Ancestors)

Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Amy Klion
• Organization: NIAID/NIH

aklion@niaid.nih.gov

301-435-8903

Study Officials

• Amy D Klion, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Drug assignment (reslizumab vs. placebo) and eosinophil count
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2010
• First Posted: April 27, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2016
• Study Completion: September 1, 2017
• Last Updated: January 27, 2022
• Results First Posted: June 1, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)