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

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ClinicalTrials.gov Identifier: NCT04188301
Recruitment Status : Enrolling by invitation
First Posted : December 5, 2019
Last Update Posted : December 31, 2020
Sponsor:
Collaborators:
Case Western Reserve University
University of Health and Allied Sciences
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE December 2, 2019
First Posted Date  ICMJE December 5, 2019
Last Update Posted Date December 31, 2020
Actual Study Start Date  ICMJE December 6, 2019
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
  • Rates/types of severe adverse events (SAEs) across study arms [ Time Frame: within 7 days following end of treatment ]
    Rates and types 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.
  • Percentage of worms killed/sterilized across study arms [ Time Frame: 18 months following treatment. ]
    The effect of three treatment regimens for killing or sterilizing 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
  • Rates of SAEs by treatment group in those with intraocular mf 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.
  • 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.
  • 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 with IDA will be compared by treatment group.
  • Effectiveness of clearing microfilariae from skin by skin snips [ Time Frame: 3, 12, & 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.
  • Effectiveness for preventing reappearance of microfilariae in the skin by skin snips [ Time Frame: 12 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 with IDA will be compared by treatment arm.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of IDA for Onchocerciasis
Official Title  ICMJE Safety and Efficacy of Combination Therapy With Ivermectin, Diethylcarbamazine, and Albendazole (IDA) for Individuals With Onchocerciasis
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be split into two strata - those without ocular Mf detected six months after ivermectin pretreatment in the Part I preceding study AND without ocular Mf detected at baseline in the part II study will be in stratum 1. Those participants with ocular Mf detected 6 months after ivermectin pretreatment in the preceding study OR with ocular Mf detected at the baseline exam for this study will be in stratum 2. Stratum 1 will be enrolled first, followed by stratum 2. Members of each stratum will be evenly randomized into one of three treatment arms:

  1. IVM + ALB - Single dose of oral IVM (150 µg/kg) plus ALB (400 mg) (IVM/ALB)
  2. IDA x 1 dose - Single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
  3. IDA x 3 doses -Once daily for 3 days oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
Masking: None (Open Label)
Masking Description:
While this is an open label study and there is no placebo treatment group, all efforts will be made to ensure that that medical/technical staff assessing skin Mf, adverse events (AEs) and ophthalmological findings will be unaware of initial baseline skin and ocular Mf findings and treatment arm as best as possible.
Primary Purpose: Treatment
Condition  ICMJE Onchocerciasis
Intervention  ICMJE
  • Drug: IVM w/ ALB
    Participants will be given a single dose of oral IVM (150 µg/kg) plus ALB (400 mg) (IVM/ALB)
    Other Name: IA
  • 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 Name: IVM/DEC/ALB (x1)
  • 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 Name: IVM/DEC/ALB (x3)
Study Arms  ICMJE
  • Active Comparator: IVM + ALB
    Single dose of oral IVM (150 µg/kg) plus ALB (400 mg)
    Intervention: Drug: IVM w/ ALB
  • Experimental: IDA x 1 dose
    Single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
    Intervention: Drug: Single dose of IDA
  • Experimental: IDA x 3 doses
    Once daily for 3 days oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
    Intervention: Drug: Three daily doses of IDA
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: December 4, 2019)
201
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ghana
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04188301
Other Study ID Numbers  ICMJE 201910085
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE
  • Case Western Reserve University
  • University of Health and Allied Sciences
Investigators  ICMJE
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
PRS Account Washington University School of Medicine
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP