LoiasisPhase 2NCT02644525
Efficacy and Microfilaricidal Kinetics of Imatinib for the Treatment of Loa Loa
A Phase 2 study testing Imatinib Mesylate in people with Loiasis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cameroon.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Loiasis
- What is being tested?
- Imatinib Mesylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCameroon
- Study dates
- 16 Sep 2019to 19 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Cameroon1 site
Centre de Recherche sur les Filarioses et Autres Maladies Tropicales
Mbalmayo
About this study
Official title: A Double-blinded, Randomized, Placebo-Controlled Dose Escalation Study to Examine the Efficacy and Microfilaricidal Kinetics and Safety of Imatinib for the Treatment of Loa Loa (A Pilot Study)
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.
Read more
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.
Read the detailed description
With the discovery that people experiencing severe treatment reactions following mass drug administration (MDA) with ivermectin for onchocerciasis and lymphatic filariasis control were co-infected with Loa loa, there has been a need for new filaricidal drugs. Currently, Loa loa infection, considered relatively nonpathogenic, is not treated in endemic areas. However, because treatment for Loa loa can result in toxicity in people who are being concurrently treated for onchocerciasis and lymphatic filariasis, finding a new treatment for Loa loa has become a priority. Imatinib has recently been shown to be microfilaricidal in vitro at concentrations physiologically achievable after a single oral dose in humans. The current standard in loiasis treatment outside of endemic areas is to treat those with low microfilarial (MF) levels (less than approximately 8,000MF/mL) with diethylcarbamazine (DEC). However, at high MF concentrations (>20,000 MF/mL) serious side effects including encephalopathy and death have occurred with administration of DEC or ivermectin, a widely distributed microfilaricide throughout Africa. In endemic areas, this risk is avoided by not treating loiasis altogether. The adverse reactions are believed to be due release of a large antigen load due to rapid killing of large numbers of MF. The rapidity of killing is believed to be the main driver of these reactions seen at high MF counts. The purpose of this study is to assess how imatinib acts as a slow microfilaricide at levels (<2,500 MF/mL) that have been safely treated previously with DEC and ivermectin. We aim to perform a dose escalation study to identify the minimum single oral dose that will be effective as a slow microfiaricidal drug against Loa loa. If imatinib is found to be effective and have kinetics which favor slow microfilarial killing, then this can serve as the basis for a larger study in which patients with very high microfilarial loads would be treated, as this is the at risk population in current MDA campaigns. This is a double blind, randomized, pilot phase 2 dose-escalation trial. Subjects will receive a dose of imatinib at 200, 400 or 600 (n = 5 each). Symptoms and blood microfilarial concentration will be assessed at baseline, daily for the first 7 days, then weekly for the next 21 days, then at 3, 6, and 12 months. These will be compared against an untreated placebo-controlled group of 5 subjects who will have the same data collected at these respective days.
- Conditions
- Loiasis
- Being tested
- Imatinib Mesylate, Placebo
- Keywords
- Cameroon, Filaricidal, Randomized, Blinded, Diethylcarbamazine, Imatinib, Loa loa
- Medical subject headings
- Loiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib MesylateDrug
Also called Gleevec
A single dose of imatinib 200mg PO is given
Imatinib MesylateDrug
Also called Gleevec
A single dose of imatinib 400mg PO is given
Imatinib MesylateDrug
Also called Gleevec
A single dose of imatinib 600mg PO is given
PlaceboDrug
A single dose of placebo pill is given
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects given vitamin placebo Receives: Drug: Placebo |
| Imatinib 200mg | Experimental | Subjects given a single dose of imatinib 200mg PO Receives: Drug: Imatinib Mesylate |
| Imatinib 400mg | Experimental | Subjects given a single dose of imatinib 400mg PO Receives: Drug: Imatinib Mesylate |
| Imatinib 600mg | Experimental | Subjects given a single dose of imatinib 600mg PO Receives: Drug: Imatinib Mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Days 1-7, 14, 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2016 (estimated)
- Study start16 Sep 2019
- Primary completion31 Dec 2020
- Study completion19 Mar 2021
Why it stopped: Planned interim analysis demonstrated futility of intervention
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LoiasisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Elise M O'Connell, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02644525
- Sponsor's protocol ID
- 999916042
- Other IDs
- 16-I-N042
- Status last verified
- Mar 2021
- First submitted
- 31 Dec 2015
- Last updated
- 7 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 14975061O'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.
PubMed 29166233Twum-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.
PubMed 14975064
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blinded, Randomized, Placebo-Controlled Dose Escalation Study to Examine the Efficacy and Microfilaricidal Kinetics and Safety of Imatinib for the Treatment of Loa Loa (A Pilot Study)
- ClinicalTrials.gov ID
- NCT02644525
- Acronym / sponsor ID
- 999916042
- Conditions
- Loiasis
- Keywords
- Cameroon, Filaricidal, Randomized, Blinded, Diethylcarbamazine, Imatinib, Loa loa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Planned interim analysis demonstrated futility of intervention
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 16 Sep 2019 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 19 Mar 2021 (actual)
- First posted
- 1 Jan 2016 (estimated)
- Results
- Posted 7 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
With the discovery that people experiencing severe treatment reactions following mass drug administration (MDA) with ivermectin for onchocerciasis and lymphatic filariasis control were co-infected with Loa loa, there has been a need for new filaricidal drugs. Currently, Loa loa infection, considered relatively nonpathogenic, is not treated in endemic areas. However, because treatment for Loa loa can result in toxicity in people who are being concurrently treated for onchocerciasis and lymphatic filariasis, finding a new treatment for Loa loa has become a priority. Imatinib has recently been shown to be microfilaricidal in vitro at concentrations physiologically achievable after a single oral dose in humans. The current standard in loiasis treatment outside of endemic areas is to treat those with low microfilarial (MF) levels (less than approximately 8,000MF/mL) with diethylcarbamazine (DEC). However, at high MF concentrations (>20,000 MF/mL) serious side effects including encephalopathy and death have occurred with administration of DEC or ivermectin, a widely distributed microfilaricide throughout Africa. In endemic areas, this risk is avoided by not treating loiasis altogether. The adverse reactions are believed to be due release of a large antigen load due to rapid killing of large numbers of MF. The rapidity of killing is believed to be the main driver of these reactions seen at high MF counts. The purpose of this study is to assess how imatinib acts as a slow microfilaricide at levels (<2,500 MF/mL) that have been safely treated previously with DEC and ivermectin. We aim to perform a dose escalation study to identify the minimum single oral dose that will be effective as a slow microfiaricidal drug against Loa loa. If imatinib is found to be effective and have kinetics which favor slow microfilarial killing, then this can serve as the basis for a larger study in which patients with very high microfilarial loads would be treated, as this is the at risk population in current MDA campaigns. This is a double blind, randomized, pilot phase 2 dose-escalation trial. Subjects will receive a dose of imatinib at 200, 400 or 600 (n = 5 each). Symptoms and blood microfilarial concentration will be assessed at baseline, daily for the first 7 days, then weekly for the next 21 days, then at 3, 6, and 12 months. These will be compared against an untreated placebo-controlled group of 5 subjects who will have the same data collected at these respective days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSubjects given vitamin placebo |
| Imatinib 200mg | Experimental | Drug: Imatinib MesylateSubjects given a single dose of imatinib 200mg PO |
| Imatinib 400mg | Experimental | Drug: Imatinib MesylateSubjects given a single dose of imatinib 400mg PO |
| Imatinib 600mg | Experimental | Drug: Imatinib MesylateSubjects given a single dose of imatinib 600mg PO |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib MesylateAlso: GleevecA single dose of imatinib 200mg PO is given | Drug | Imatinib 200mg |
| Imatinib MesylateAlso: GleevecA single dose of imatinib 400mg PO is given | Drug | Imatinib 400mg |
| Imatinib MesylateAlso: GleevecA single dose of imatinib 600mg PO is given | Drug | Imatinib 600mg |
| PlaceboA single dose of placebo pill is given | Drug | Placebo |
Primary outcome
Percent of Baseline Loa Loa Microfilariae
Time frame: Days 1-7, 14, 21
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14975061Boussinesq 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.
- Background: PubMed 29166233O'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.
- Background: PubMed 14975064Twum-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.
Related trials for Loiasis
Not yet recruitingPhase 3
21-day Double-blind Trial of Albendazole in Adults With Loa Loa Microfilaremia
Loiasis With Positive Blood Microfilaremia, Loiasis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elise M O'Connell, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib Mesylate in people with Loiasis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Cameroon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cameroon. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Baseline Loa Loa Microfilariae (time frame: Days 1-7, 14, 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02644525, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2022.