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Moxidectin for LF, Cote d'Ivoire (DOLF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04410406
Recruitment Status : Active, not recruiting
First Posted : June 1, 2020
Last Update Posted : October 6, 2022
Sponsor:
Collaborators:
Case Western Reserve University
Regional Hospital of Agboville, Southern Cote d'Ivoire
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The purpose of this study is to determine whether moxidectin (Mox) will be more effective than ivermectin (IVM) when used in single-dose combination therapies for lymphatic filariasis (LF).

Condition or disease Intervention/treatment Phase
Lymphatic Filariasis Drug: Ivermectin Drug: Diethylcarbamazine Drug: Albendazole Drug: Moxidectin Phase 3

Detailed Description:

This study will test the hypothesis that Moxidectin combination therapies are superior to ivermectin combination therapies for achieving sustained clearance of W. bancrofti microfilaremia.

This trial is designed as single-site, Phase III, randomized, open-label, masked-observer superiority trial with four treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine + albendazole (IDA), and moxidectin + diethylcarbamazine + albendazole (MoxDA). The primary endpoint is the proportion of participants achieving complete clearance of microfilaremia at 12 months (IA vs. MoxA comparison) or 24 months (IDA vs. MoxDA comparison). Block randomization by gender will be used to assign treatment arms.

The first 48 participants (12 each arm) will be treated at Agboville Hospital in Cote d'Ivoire at the Centre de Recherche de Filariose with inpatient AE monitoring and collection of post-treatment plasma drug levels (Part 1). For Part 1, active AE surveillance will be conducted in the hospital on days 1, 2, and 3, post-treatment, and in the participant's village of residence on day 7 post-treatment and passive surveillance will be conducted by trained village health workers on days 4-6. An interim safety analysis will take place after Part 1. If no safety concerns are identified, the remainder of the participants will be treated in their home villages, with active AE monitoring on days 1 and 2 post-treatment (Part 2) with passive surveillance by trained village health workers on days 3-7. Any participant in either Part 1 or Part 2 experiencing AEs of grade 2 or higher will be followed until adverse event (AE) severity falls below grade 2. Follow-up assessments for efficacy of treatments for all participants (Parts 1 and 2) will be conducted at 6, 12, 24, and 36 months.

The study includes both safety and efficacy analyses. The safety assessment (Part 1 only) ends 7 days after treatment (unless AEs remain grade 2 or higher). The efficacy assessment (Parts 1 and 2 combined) ends when participants are retested for filarial infection 36 months post-treatment. Participants in the IA arm will receive IA annually (standard of care). Participants in the other arms will receive the assigned treatment at baseline; those found to be microfilaremic at 24 months post-treatment will be retreated with the same treatment received at baseline. If clearance of microfilariae (Mf) at 12 months in the IA arm is superior to Mf clearance in the MoxA arm, the MoxA group will be switched to annual IA treatment.

The study design does not currently include stratification, nor do any sub-studies. However, the study may stratify based on pre-treatment Mf levels if high variability among pre-screening Mf counts is observed.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 164 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This trial is a single-site, Phase III, randomized, open-label, masked-observer superiority trial with four treatment arms (IA, MoxA, IDA, and MoxDA). Block randomization by gender will be used to assign treatment arms.
Masking: None (Open Label)
Masking Description: Recognizing that number and appearance of tablets received in each study arm will be noticeably different, this study will not be completely masked to participants or care providers. To minimize bias, administration of study medications will be performed by a staff member with no role in assessing AEs. AE assessments and all other outcome measures will be assessed by observers masked to the treatment assignment as best as possible.
Primary Purpose: Treatment
Official Title: A Clinical Trial to Assess the Safety and Efficacy of Moxidectin Combination Treatments vs. Ivermectin Combination Treatments for Bancroftian Filariasis
Actual Study Start Date : August 20, 2020
Estimated Primary Completion Date : September 1, 2023
Estimated Study Completion Date : September 1, 2023


Arm Intervention/treatment
Active Comparator: IA (Ivermectin + Albendazole)
Participants will receive one oral dose of Ivermectin (IVM) 200 µg/kg + Albendazole (ABZ) 400 mg (IA) annually for 24 months.
Drug: Ivermectin
Ivermectin (IVM) 200 µg/kg
Other Name: Stromectol

Drug: Albendazole
Albendazole (ABZ) 400 mg

Active Comparator: MoxA (Moxidectin + Albendazole)
Participants will receive one oral dose of Mox 8 mg + ABZ 400 mg. Participants who are Mf positive at 24 months will be retreated with MoxA at the same dosage.
Drug: Albendazole
Albendazole (ABZ) 400 mg

Drug: Moxidectin
Moxidectin (Mox) 8 mg

Active Comparator: IDA (Ivermectin + Diethylcarbamazine + Albendazole)
Participants will receive one oral dose of IVM 200 µg/kg + Diethylcarbamazine (DEC) 6mg/kg + ABZ 400 mg. Participants who are Mf positive at 24 months will be retreated with IDA at the same dosage.
Drug: Ivermectin
Ivermectin (IVM) 200 µg/kg
Other Name: Stromectol

Drug: Diethylcarbamazine
Diethylcarbamazine (DEC) 6mg/kg
Other Names:
  • Diethylcarbamazine citrate
  • Hetrazan

Drug: Albendazole
Albendazole (ABZ) 400 mg

Active Comparator: MoxDA (Moxidectin + Diethylcarbamazine + Albendazole)
Participants will receive one oral dose of Mox 8 mg + DEC 6mg/kg + ABZ 400 mg. Participants who are Mf positive at 24 months will be retreated with MoxDA at the same dosage.
Drug: Diethylcarbamazine
Diethylcarbamazine (DEC) 6mg/kg
Other Names:
  • Diethylcarbamazine citrate
  • Hetrazan

Drug: Albendazole
Albendazole (ABZ) 400 mg

Drug: Moxidectin
Moxidectin (Mox) 8 mg




Primary Outcome Measures :
  1. Clearance of microfilaremia (IA vs. MoxA) [ Time Frame: 12 months ]
    The proportion of participants in IA and MoxA study arms with complete clearance of W. bancrofti microfilaremia at 12 months after treatment.

  2. Clearance of microfilaremia (IDA vs. MoxDA) [ Time Frame: 24 months ]
    The proportion of participants in IDA and MoxDA study arms with complete clearance of W. bancrofti microfilaremia at 24 months after treatment.


Secondary Outcome Measures :
  1. Clearance of microfilaremia [ Time Frame: 6, 12, 24, & 36 months ]
    The proportion of participants in each study arm with complete clearance of W. bancrofti microfilaremia at 6, 12, 24, & 36 months after treatment.

  2. Reduction in Mf counts [ Time Frame: Baseline, 6, 12, & 24 months ]
    Reduction in microfilariae counts (relative to baseline) at 6, 12, & 24 months

  3. Reduction in circulating filarial antigen (CFA) counts [ Time Frame: Baseline, 6, 12, & 24 months ]
    Reduction in circulating filarial antigen (CFA) counts (relative to baseline) at 6, 12, & 24 months

  4. Inactivation of adult worm nests [ Time Frame: 6, 12, & 24 months ]
    Inactivation of adult worm nests as assessed by scrotal ultrasound at 6, 12, and 24 months after treatment

  5. Frequency and severity of AEs [ Time Frame: From baseline treatment to 7 days post-treatment ]
    Frequency and severity of AEs during the first 7 days after treatment.

  6. Plasma levels of drugs/metabolites post treatment [ Time Frame: Baseline, 2, 3, 4, 6, 12, 24, & 48 hours post-treatment ]
    Noncompartmental pharmacokinetic analyses of DEC, ABZ, ABZSO, ABZSO2, IVM and Mox concentrations will be conducted using WinNonlin (Pharsight Corporation; Cary, North Carolina, USA). Drug plasma concentrations and computed pharmacokinetic parameters will be listed by subject and summarized by drug or metabolite (geometric mean with coefficient of variation, arithmetic mean with standard deviation, minimum, maximum, number of observations). Individual and geometric mean (by time) concentrations versus time will be plotted for each treatment group on both linear and natural logarithm scales.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Provision of signed and dated informed consent form
  • Male or female, aged 18-70 years
  • In good general health as evidenced by medical history
  • Peripheral night blood W. bancrofti Mf levels ≥40 Mf/mL
  • No history of taking antifilarial medications in past 12 months
  • Resident of the study area with no plans to change residence in the next 36 months
  • For women of childbearing potential, willing to use appropriate method of contraception for one month following each treatment

Exclusion Criteria:

  • Pregnancy or currently breastfeeding
  • Known allergic reactions to any of the study medications
  • Evidence of severe or systemic comorbidities (aside from features of filarial disease), as judged by the principal investigator
  • Baseline biochemical abnormalities, as indicated by AST, ALT, or creatinine > 2 times the upper limit of normal
  • Evidence of urinary tract infection as indicated by 3+ nitrites on dipstick (individuals with 1+ or 2+ nitrites will not be excluded) or underlying chronic kidney disease as indicated by 3+ protein or 3+ blood on urine dipstick exam
  • Hgb < 7 gm/dL (any such individuals will be referred to the local health center for evaluation and treatment)
  • Positive skin snip for onchocerciasis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04410406


Locations
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Côte D'Ivoire
Regional Hospital of Agboville, Southern Cote d'Ivoire
Agboville, Côte D'Ivoire
Sponsors and Collaborators
Washington University School of Medicine
Case Western Reserve University
Regional Hospital of Agboville, Southern Cote d'Ivoire
Investigators
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Principal Investigator: Philip Budge, MD, PhD Washington University School of Medicine
Principal Investigator: Catherine Bjerum, MD, MPH Case Western Reserve University
Principal Investigator: Toki Pascal Gabo, MD Regional Hospital of Agboville, Southern Cote d'Ivoire
Principal Investigator: Benjamin Koudou, PhD Regional Hospital of Agboville, Southern Cote d'Ivoire
Additional Information:
Publications:

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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04410406    
Other Study ID Numbers: 202005076
First Posted: June 1, 2020    Key Record Dates
Last Update Posted: October 6, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified datasets used for published results will be shared publically through a journal or other open source data repository so that the broader scientific community can access it. Datasets used for published results will be shared publically 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 outside of the study team.

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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
Keywords provided by Washington University School of Medicine:
moxidectin
ivermectin
Additional relevant MeSH terms:
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Filariasis
Elephantiasis, Filarial
Elephantiasis
Spirurida Infections
Secernentea Infections
Nematode Infections
Helminthiasis
Parasitic Diseases
Infections
Lymphedema
Lymphatic Diseases
Vector Borne Diseases
Ivermectin
Albendazole
Moxidectin
Diethylcarbamazine
Molecular Mechanisms of Pharmacological Action
Antiparasitic Agents
Anti-Infective Agents
Anthelmintics
Anticestodal Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents
Antinematodal Agents
Filaricides
Lipoxygenase Inhibitors