Efficacy and Microfilaricidal Kinetics of Imatinib for the Treatment of Loa Loa

NCT02644525 | Terminated Phase 2 Results

• 2 other identifiers: 99991604216-I-N042
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Many people who live in west or central Africa are at risk for infection from a very small worm called Loa loa. This infection is acquired through the bite of a fly. Baby worms called microfilariae live in the blood. The infection most commonly causes skin itching, mild temporary limb swelling, and sometimes a adult worm can be seen in the white of the eye of an infected individual. Very rarely, people with this infection can develop problems with the kidneys and heart as a result of the worm's effect on the immune system. Because the vast majority of people with the infection have minimal symptoms, people in Cameroon usually do not get treated. But infection with Loa loa can cause serious problems in people who are being treated for infections with other parasites (namely, river blindness and lymphatic filariasis). Researchers want to find out of a drug called imatinib can treat Loa loa infection so that patients with this infection can safely receive other drugs to cure river blindness and lymphatic filariasis. Researchers believe imatinib can be a safe drug to use on Loa loa, because in the lab this drug kills the worms slowly, whereas other drugs which can cause treatment reactions usually kill the worms very quickly. Objective: To test if imatinib can treat Loa loa infection by killing the worms slowly. Eligibility: People ages 18-65 with non-severe Loa loa infection who are otherwise healthy Design: Participants will be screened with a physical exam and blood and urine tests. Participants will have a baseline visit. This will include a physical exam and blood and urine tests. It may include a stool sample. Participants will be randomly assigned to get 1 dose of either imatinib or a placebo. Participants will return to the clinic every day for 1 week, then once a week for 3 weeks. Visits will include a physical exam and blood tests. They will have urine tests in the first week. Participants will have follow-up visits 3, 6, and 12 months after taking the imatinib or placebo. These include a physical exam and blood tests. They may include urine and stool samples. If participants develop side effects, they will be treated for them.

Conditions

Loiasis

Keywords

Cameroon; Filaricidal; Randomized; Blinded; Diethylcarbamazine; Imatinib; Loa loa

Outcome Measures

Primary Outcomes (1)

• Percent of Baseline Loa Loa Microfilariae

  Percent of baseline Loa loa microfilariae as determined by concentrated peripheral blood smear. Daily measurements will be taken the first week, followed by measurements at day 14 and day 21

  Days 1-7, 14, 21

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Subjects given vitamin placebo

Drug: Placebo

Imatinib 200mg

EXPERIMENTAL

Subjects given a single dose of imatinib 200mg PO

Drug: Imatinib Mesylate

Imatinib 400mg

EXPERIMENTAL

Subjects given a single dose of imatinib 400mg PO

Drug: Imatinib Mesylate

Imatinib 600mg

EXPERIMENTAL

Subjects given a single dose of imatinib 600mg PO

Drug: Imatinib Mesylate

Interventions

Imatinib Mesylate DRUG

A single dose of imatinib 200mg PO is given

Also known as: Gleevec

Imatinib 200mg

Placebo DRUG

A single dose of placebo pill is given

Placebo

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years old and less than or equal to 65 years
• Loa loa microfilaremia \>500 MF/mL and \<2500 MF/mL at screening visit.
• Subject has the capacity to understand the potential risks and benefits and consents to protocol indicated blood draws and follow up visits.

You may not qualify if:

• Women under 45 years of age, or over 45 years of age with a menstrual period in the preceding 12 months.
• Currently breastfeeding
• Currently taking daily medications
• Known chronic medical conditions, including but not limited to diabetes, renal failure, liver disease, seizure disorder, HIV, malignancy, psychiatric disorder, or any conditions which within the investigators judgement are deemed to be clinically significant.
• W. bancrofti serologic positivity against Wb123
• O. volvulus serologic positivity against Ov16
• HIV by history or clinical signs of HIV/AIDS (e.g. oral thrush, oral/skin lesions of Kaposi s sarcoma, etc.)
• Any of the following lab abnormalities: Creatinine \>1.5, Platelets \<100,000/mL, Hemoglobin \<12g/dL, alanine aminotransferase or aspartate aminotransferase \>60 U/L, total bilirubin \>1.7mg/dL, absolute neutrophil count equal to or less than 1500/mm(3).
• Any condition that, in the opinion of the PI, may substantially increase the risk of participation, including any contraindication to imatinib.

Sponsors & Collaborators

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

Study Sites (1)

Centre de Recherche sur les Filarioses et Autres Maladies Tropicales

Mbalmayo, Cameroon

Location

Related Publications (3)

• Boussinesq M, Gardon J, Gardon-Wendel N, Chippaux JP. Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon. Filaria J. 2003 Oct 24;2 Suppl 1(Suppl 1):S4. doi: 10.1186/1475-2883-2-S1-S4.

  PMID: 14975061 BACKGROUND

• O'Connell EM, Nutman TB. Reduction of Loa loa Microfilaremia with Imatinib - A Case Report. N Engl J Med. 2017 Nov 23;377(21):2095-2096. doi: 10.1056/NEJMc1712990. No abstract available.

  PMID: 29166233 BACKGROUND

• Twum-Danso NA. Loa loa encephalopathy temporally related to ivermectin administration reported from onchocerciasis mass treatment programs from 1989 to 2001: implications for the future. Filaria J. 2003 Oct 24;2 Suppl 1(Suppl 1):S7. doi: 10.1186/1475-2883-2-S1-S7.

  PMID: 14975064 BACKGROUND

MeSH Terms

Conditions

Loiasis

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Elise O'Connell, MD, Principal Investigator
• Organization: Laboratory of Parasitic Diseases, NIAID/NIH

oconnellem@mail.nih.gov

301-661-0172

Study Officials

• Elise M O'Connell, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2015
• First Posted: January 1, 2016
• Study Start: September 16, 2019
• Primary Completion: December 31, 2020
• Study Completion: March 19, 2021
• Last Updated: June 7, 2022
• Results First Posted: June 7, 2022

Record last verified: 2021-03

Locations

CA (1)