Safety and Efficacy of IDA for Onchocerciasis (DOLF IDA/Oncho)

April 15, 2023 updated by: Washington University School of Medicine

Safety and Efficacy of Combination Therapy With Ivermectin, Diethylcarbamazine, and Albendazole (IDA) for Individuals With Onchocerciasis

This DOLF study will investigate the safety and effectiveness of IDA treatment in persons with onchocerciasis when it is administered after pre-treatment with ivermectin to clear or greatly reduce microfilariae from the skin and eyes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will provide preliminary data on the safety of IDA treatment in persons with onchocerciasis when it is administered after pre-treatment with IVM to clear or greatly reduce microfilariae from the skin and eyes. Widespread use of IDA following IVM pretreatment (I/IDA) has the potential to greatly accelerate elimination of lymphatic filariasis (LF) in African countries that are co-endemic for LF and onchocerciasis. study later.

This study will also assess the efficacy of IDA for killing and sterilizing adult filarial worms. An improved macrofilaricidal treatment would be a major advance for the global program to eliminate onchocerciasis. Since the safety and efficacy objectives are both very important, we have included dual primary objectives for the study.

Primary objectives:

  • Safety: To compare rates and types of severe adverse events (grade 3 or higher) that occur within 7 days following 1 day or 3 days of treatment with triple drug treatment ("IDA" = diethylcarbamazine (DEC) with ivermectin (IVM) and albendazole (ALB)) with the comparator regimen of 1 day of treatment with ivermectin and albendazole (IA) in persons with active Onchocerca volvulus infections after pretreatment with ivermectin alone.
  • Efficacy: To compare the effect of three treatment regimens (1 day of IDA, 3 days of IDA, or IA) for killing or sterilizing adult female O. volvulus worms based on the percentage of all adult female worms in nodules that are alive with embryos in the uterus 18 months after treatment.

This is an open label, randomized clinical trial.

Study Type

Interventional

Enrollment (Actual)

154

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ghana
      • Hohoe, Ghana
        • University of Health and Allied Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women who were previously enrolled in the preceding Part I study (Protocol ID#201804116) and residing in the study area
  • Must have at least palpable subcutaneous nodule (onchocercoma)
  • Participants with baseline skin Mf counts less than or equal to 3 Mf/mg at the time of enrollment into the Part I study (Protocol ID#201804116)

Exclusion Criteria:

  • Pregnant and breastfeeding mothers within 1 month of giving birth

  • Severe eye disease at baseline including uveitis, severe glaucoma, severe keratitis, and/or cataracts that interfere with visualization of the posterior segment of the eye as well as the list of ocular diseases as outlined below. All ocular disease exclusion criteria apply to either eye. Bilateral disease is not necessary to exclude a participant. A participant will be excluded if any of the criteria are met for one eye.

    1. Any cataract of any type preventing clear visualization of fundus or imaging on Optical Coherence Tomography (OCT).
    2. Severe retinal nerve fiber layer thinning in the superior and inferior quadrant analysis on Ocular Coherence Tomography of the optic nerve with a corresponding visual field defect of grade 2 or worse on the same eye.If Ocular Coherence Tomography is not available, the following exclusion criteria will apply: vertical Cup/disc ratio on fundoscopy (not by OCT reading) greater than or equal to 0.80.
    3. Intraocular pressure (IOP) greater than or equal to 25 by Goldmann tonometry .12
    4. Retinal Detachment or Retinal Break
    5. Acute ocular infection (i.e., Viral conjunctivitis, corneal ulcer, endophthalmitis)
    6. Optic Atrophy with visual field defect reproducible on confrontation visual field testing..
    7. Exam consistent with Herpes Simplex Virus eye infection
    8. Homonymous hemianopsia, quadrantanopsia, bitemporal hemianopsia, or central scotoma related to cerebral vascular disease by Automated Visual Field testing and confrontation visual field testing.
    9. Acute Angle Closure Glaucoma
    10. Gonioscopy grade 0 (slit) limiting ability to safely dilate patient
    11. Severe Tremor, blepharospasm, or other voluntary or involuntary motor condition that prevents ability to examine patient with slit lamp, OCT, gonioscopy, IOP measurement, fundus photography, and Frequency doubling technology perimetry.
    12. Cognitive impairment sufficient to prevent ability to understand and perform Visual Acuity Test with Tumbling E chart, confrontation visual field, slit lamp exam, or any other ocular exam component.
    13. Optic nerve edema
    14. Active retinopathy or retinitis not attributable to onchocercal disease
    15. History of uveitis not associated with onchocercal disease
    16. Any pre-existing chorioretinal scar or retinal degeneration and other significant retinal pathologies (foveomacular schisis, dystrophies, arterial macroaneurysms etc) involving the macula.
    17. Severe ocular pain, that patient rates as 9 or 10 out of 10 pain.
    18. Best corrected or pinhole visual acuity worse than 6/60 (20/200)
    19. Age related macular degeneration (AMD)
  • Significant comorbidities such as renal insufficiency, liver failure, or any other acute or chronic illness identified by study clinicians and investigators that interferes with the participant's ability to go to school or work or perform routine household chores.
  • Prior allergic / hypersensitivity reactions or intolerance to IVM, ALB, or DEC.
  • Treatment with IVM outside of the study after the pre-treatment clearing dose provided in the Part I study.
  • >5 motile Mf in the anterior chamber in either eye at the time of enrollment (after pre-treatment with IVM).
  • Any Mf identified in the posterior segment of the eye at the time of enrollment (six months after pre-treatment with IVM).
  • Any other condition identified by study clinicians or investigators that may preclude participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: IVM + ALB
Single dose of oral IVM (150 µg/kg) plus ALB (400 mg)
Drug: IVM w/ ALB
Participants will be given a single dose of oral IVM (150 µg/kg) plus ALB (400 mg) (IVM/ALB)
Other Names:
  • IA
Experimental: IDA x 1 dose
Single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
Drug: Single dose of IDA
Participants will be given a single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
Other Names:
  • IVM/DEC/ALB (x1)
Experimental: IDA x 3 doses
Once daily for 3 days oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
Drug: Three daily doses of IDA
Participants will be given one daily dose for 3 days of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
Other Names:
  • IVM/DEC/ALB (x3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of Severe Adverse Events (SAEs) Across Study Arms
Time Frame: Within 7 days following end of treatment
Rates of severe adverse events (grade 3 or higher) following 1-day or 3-day triple drug treatment will be compared against those of the comparator regimen of 1 day of IVM/ALB.
Within 7 days following end of treatment
Percentage of Worms Killed Across Study Arms
Time Frame: 18 months following treatment.
The effect of three treatment regimens for killing adult female O. volvulus worms will be compared based on the percentage of all adult female worms in nodules that are alive with embryos in the uterus 18 months after treatment.
18 months following treatment.
Percentage of Worms Sterilized Across Study Arms
Time Frame: 18 months following treatment.
The effect of three treatment regimens for sterilizing adult female O. volvulus worms will be compared based on the percentage of all adult female worms that are fertile in the nodules 18 months after treatment.
18 months following treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of SAEs by Treatment Group in Those With Intraocular Microfilariae Just Prior to Treatment With IDA
Time Frame: within 7 days following end of treatment
Rates of adverse events grade 3 or higher that occur within 7 days of treatment in the subset of participants who have intraocular microfilariae just prior to treatment with IDA will be compared by treatment group.
within 7 days following end of treatment
Rates of Ocular Adverse Events (Any Grade) by Treatment Group
Time Frame: within 3 months of treatment with IDA
Rates of ocular adverse events of any grade within 3 months will be compared by treatment group.
within 3 months of treatment with IDA
Effectiveness of Killing Adult Female Worms
Time Frame: 18 months following treatment
The effectiveness of three treatment regimens for killing adult female O. volvulus worms based on the percentage of all adult female worms in nodules that are alive 18 months after treatment.
18 months following treatment
Effectiveness of Clearing Microfilariae From Skin by Skin Snips
Time Frame: Baseline, 3 months, 12 months, & 18 months following treatment.
The effectiveness of three treatment regimens for complete clearance of microfilariae from the skin as determined by skin snips at 3, 12, and 18 months after treatment with IDA will be compared by treatment arm.
Baseline, 3 months, 12 months, & 18 months following treatment.
Effectiveness for Preventing Reappearance of Microfilariae in the Skin by Skin Snips
Time Frame: Baseline, 12 months, and 18 months following treatment
The effectiveness of three treatment regimens for preventing reappearance of microfilariae in the skin as determined by skin snips at 12 and 18 months after treatment will be compared by treatment arm. Measured by the presence of microfilariae in skin snips.
Baseline, 12 months, and 18 months following treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Case Western Reserve University
University of Health and Allied Sciences

Investigators

  • Principal Investigator: Gary Weil, MD, Washington University School of Medicine
  • Principal Investigator: Christopher King, MD, PhD, Case Western Reserve University
  • Principal Investigator: Nicholas Opoku, MB, CHB, MSC, University of Health and Allied Sciences, Hohoe, Ghana

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2019

Primary Completion (Actual)

March 14, 2022

Study Completion (Actual)

June 1, 2022

Study Registration Dates

First Submitted

December 2, 2019

First Submitted That Met QC Criteria

December 4, 2019

First Posted (Actual)

December 5, 2019

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

April 15, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201910085

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Datasets used for published results will be shared publicly through a journal or other open source data repository so that the broader scientific community can access it. Only de-identified data will be shared publicly.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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