Study to Assess Adverse Events, Change in Disease Activity and How Oral ABBV-4083 Capsules When Given Alone or In Combination With Albendazole Capsules Moves in The Body of Adult Participants With Onchocerca Volvulus Infection

A Phase-II, Randomised, Double-blind, Parallel-group, Proof-of-concept Trial to Investigate ABBV-4083 Given for 7 or 14 Days or in Combination With Albendazole in Subjects With Onchocerca Volvulus Infection, Comprising: Part 1 to Investigate Safety, Tolerability, Efficacy for Dose-Ranging and Pharmacokinetics; Part 2 to Investigate Efficacy of Selected Doses, Safety, Tolerability and Pharmacokinetics

Onchocerciasis is a major public health problem in affected countries that causes disease-induced disability, and overall loss of economic productivity. The purpose of this study is to determine how safe and effective ABBV-4083 in combination with albendazole is in treating participants with Onchocerciasis.

ABBV-4083 is an investigational drug being developed for the treatment of onchocerciasis. This study is conducted in 2 parts. In part 1, participants are randomly assigned to 1 of 5 groups, called treatment arms to determine the most efficient treatment combination. Each group receives a different treatment. In part 2, participants are randomly assigned to 1 of 4 treatment arms. Approximately 444 or 486 adult participants with a diagnosis of onchocerciasis will be enrolled in approximately 2 sites in Democratic Republic of Congo.

Participants in Part 1 will receive different treatment combinations of ABBV-4083 and/or albendazole and/or matching placebo capsules for 14 days. Participants in Part 2 will most effective treatment combination determined in Part 1 for 14 days followed by ivermectin or matching placebo capsules at Month 6. Duration of treatment is 24 months.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects.

Study Overview

• Status: Terminated
• Conditions: Onchocerciasis
• Intervention / Treatment: Drug: ABBV-4083; Drug: Placebo for ABBV-4083; Drug: Placebo for Albendazole; Drug: Albendazole; Drug: Ivermectin; Drug: Placebo for Ivermectin

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sabine Specht, PhD; Phone Number: +41796981351; Email: sspecht@dndi.org

Study Locations

• Congo, The Democratic Republic of the
  • Kongo Central
    • Kimpese, Kongo Central, Congo, The Democratic Republic of the
      • Hôpital Général de Référence de Kimpese
  • Kwilu
    • Masi-Manimba, Kwilu, Congo, The Democratic Republic of the
      • Hôpital Général de Référence de Masi-Manimba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Onchocerca volvulus infection at time of Screening:

  • Presence of at least one excisable subcutaneous nodule/ onchocercoma detected on palpation;
  • O. volvulus infection diagnosed by skin snip method: documented mfpositivity on skin assessment on at least 2 out of 4 skin snips.
• Body weight > 40 kg at Screening.
• For women of child-bearing potential, acceptance of the requirement to use a highly effective form of birth control from Day 0 until at least 1 month after the final intake of study drug (Part 1: day 43; Part 2: 1 month after the administration of ivermectin or matching placebo at the Month 6 visit). Choice of birth control method must be clearly documented.

Exclusion Criteria:

• Participation in any studies other than purely observational studies within 3 months prior to Screening, or during the trial, or within 5 times the half-life of the drug tested in the previous clinical trial or is currently in the follow-up period for any clinical trial.
• Any vaccination within 4 weeks prior to investigational medicinal product (IMP) administration.
• Acute infection and/or febrile illness requiring therapy within 14 days prior to IMP administration.

• Administration of medication or herbal preparations as follows:

  • Administration of any medication (with the exception of diclofenac, paracetamol, ibuprofen and aspirin) or herbal preparation within 14 days prior to IMP administration;
  • Use of strong CYP3A inhibitors or inducers including but not limited to ritonavir, ketoconazole, rifampicin, phenytoin, phenobarbital, carbamazepine, cimetidine within 14 days or 10 half-lives, whichever is longer, prior to IMP administration;
  • Use of other drugs known to interact with albendazole i.e. praziquantel, theophylline or dexamethasone, within 14 days or 10 half-lives, whichever is longer, prior to IMP administration;
  • Antifilarial therapies, or medication that may have an antifilarial effect.
• Requirement for and inability to avoid ivermectin during the first 6 months after IMP administration. Requirement for albendazole during the first 28 days after IMP administration or more than one dose per year thereafter given in MDA.

• Presence of any of the following at Screening, that could interfere with the objectives of the trial or the safety of the participant, in the opinion of the Investigator:

  • Abnormal physical examination or laboratory findings;
  • Any clinically significant medical condition. Including, but not limited to significant acute or chronic liver or kidney condition or cardiovascular disease, active infection, current or previous epilepsy, known human immunodeficiency virus infection, disclosed by review of medical history or concomitant medication.
• Ophthalmological history or conditions that could interfere with the objectives of the trial or compromise the safety of the subject in the opinion of the Investigator, assessed at Screening.
• History of drug or alcohol abuse within 6 months prior to IMP administration.
• Use of alcohol or drugs of abuse within 24 hours before IMP administration.
• Clinically significant history of cardiac abnormality, and/or relevant pathological abnormalities in the ECG in the screening period.
• Abnormal laboratory test results at Screening.
• History of severe drug allergy, non-allergic drug reactions, severe adverse reaction to any drug, or multiple drug allergies.
• Known hypersensitivity to any ingredient of the IMPs, including the active ingredient of ABBV-4083, macrolides, albendazole or to ivermectin or to any medication used during the study.

Blood donation within 8 weeks prior to Screening or blood transfusion received within 1 year prior to Screening.

• Coincidental infection with high Loa loa load and/or Mansonella species or Wuchereria bancrofti, based on positive laboratory test at Screening.
• Current hyperreactive onchodermatitis or severe manifestation due to onchocerciasis.
• Any other past or current condition that the Investigator feels would exclude the participant from the study or place the subject at undue risk.
• For women of child-bearing potential: pregnant, based on date of last menstrual period, and pregnancy test prior to first intake of IMP, or breastfeeding.
• Unwilling or unable to comply with the requirements of the study protocol for the entire duration of the study, in the opinion of the Investigator.
• Unable to participate in the study as per local law, if applicable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Arm A; Participants will receive ABBV-4083 + placebo for albendazole for 7 days followed by placebo for ABBV-4083 for 7 days.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Placebo for Albendazole; Oral Capsule
Experimental: Part 1: Arm B; Participants will receive ABBV-4083 + placebo for albendazole for 7 days followed by ABBV-4083 for 7 days.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for Albendazole; Oral Capsule
Experimental: Part 1: Arm C; Participants will receive ABBV-4083 + albendazole for 7 days followed by placebo for ABBV-4083 for 7 days.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Albendazole; Oral encapsulated tablets; Other Names: Zentel
Experimental: Part 1: Arm D; Participants will receive ABBV-4083 + albendazole for 3 days followed by ABBV-4083 + placebo for albendazole for 4 days followed by placebo for ABBV-4083 for 7 days.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Placebo for Albendazole; Oral Capsule; Drug: Albendazole; Oral encapsulated tablets; Other Names: Zentel
Experimental: Part 1: Arm E; Participants will receive placebo for ABBV-4083 + albendazole for 7 days followed by placebo for ABBV-4083 for 7 days.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Albendazole; Oral encapsulated tablets; Other Names: Zentel
Experimental: Part 2: Arm K; Participants will receive active regimen from Part 1 followed by ivermectin at Month 6.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Placebo for Albendazole; Oral Capsule; Drug: Albendazole; Oral encapsulated tablets; Other Names: Zentel; Drug: Ivermectin; Encapsulated Oral Tablet
Experimental: Part 2: Arm L; Participants will receive active regimen from Part 1 followed by placebo for ivermectin at Month 6.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Placebo for Albendazole; Oral Capsule; Drug: Albendazole; Oral encapsulated tablets; Other Names: Zentel; Drug: Placebo for Ivermectin; Oral Capsule
Experimental: Part 2: Arm M; Participants will receive active regimen from Part 1 followed by placebo for ivermectin or matching placebo at Month 6.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Placebo for Albendazole; Oral Capsule; Drug: Albendazole; Oral encapsulated tablets; Other Names: Zentel; Drug: Ivermectin; Encapsulated Oral Tablet; Drug: Placebo for Ivermectin; Oral Capsule
Experimental: Part 2: Arm N; Scenario 1: Participants will receive placebo for ABBV-4083 + placebo for albendazole followed by ivermectin at Month 6. Scenario 2: Participants will receive ABBV-4083 + placebo for albendazole for 7 days followed by placebo for ABBV-4083 for appropriate duration followed by ivermectin or matching placebo at Month 6.	Drug: ABBV-4083; Oral Capsule; Other Names: Tylamac; Drug: Placebo for ABBV-4083; Oral Capsule; Drug: Placebo for Albendazole; Oral Capsule; Drug: Ivermectin; Encapsulated Oral Tablet; Drug: Placebo for Ivermectin; Oral Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Status of Each Live Female Adult Worm as Without Wolbachia Endobacteria	Status of each live female adult worm as without Wolbachia endobacteria or not, is assessed by immunohistology of nodules collected after nodulectomy.	6 Months
Part 2: Status of Each Participant as Without Skin Microfilariae	Status of each participant as without skin microfilariae or not is assessed across all skin snips in each participant.	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Percentage of Live Female Adult Worms per Participant	Percentage of live female adult worms per participant assessed by histological examination of all nodules collected after nodulectomy.	24 Months
Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus per Participant	Percentage of live female adult worms with only degenerated embryos in the uterus per participant after nodulectomy.	6 Months
Part 1: Percentage of Live Female Adult Worms out of all Female Adult Worms per Participant	Percentage of live female adult worms out of all female adult worms per participant after nodulectomy.	6 Months
Part 1: Absence of Microfilariae in Nodular Tissue per Participant	Absence of microfilariae in nodular tissue per participant after nodulectomy.	6 Months
Part 1: Status of Each Participant as Without Skin Microfilariae or not	Status of each participant as without skin microfilariae or not.	Up to 6 Months
Part 1: Reduction in Skin Microfilarial Density Compared to Baseline (Week 0)	Skin microfilarial density is defined as the mean number of microfilariae/mg per participant.	Up to 6 Months
Part 1: Status of Each Live Adult Worm as Without Wolbachia Endobacteria or not	Status of each live adult worm as without Wolbachia endobacteria or not is assessed by polymerase chain reaction (PCR).	6 Months
Part 2: Status of Each Participant as Without Skin Microfilariae or not	status of each participant as without skin microfilariae or not.	18 Months
Part 2: Reduction in Skin Microfilarial Density Compared to Baseline (Week 0)	Skin microfilarial density is defined as the mean number of microfilariae/mg per participant.	Up to 24 Months
Part 2: Absence of Microfilariae in Nodular Tissue per Participant	Absence of microfilariae in nodular tissue per participant after nodulectomy.	24 Months
Part 2: Status of Each Live Adult Female Worm as Without Wolbachia Endobacteria or not	Status of each live adult female worm as without Wolbachia endobacteria or not is assessed by immunohistology.	24 Months
Part 2: Status of Each Live Adult Worm as Without Wolbachia Endobacteria or not	Status of each live adult worm as without Wolbachia endobacteria or not is assessed by polymerase chain reaction (PCR).	24 Months
Part 2: Percentage of Live Female Adult Worms With Only Degenerated Embryos in Uterus per Participant	Percentage of live female adult worms with only degenerated embryos in uterus per participant is assessed by histological examination of nodules collected after nodulectomy.	24 Months

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Drugs for Neglected Diseases initiative
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2021
• Primary Completion (Actual): August 29, 2023
• Study Completion (Actual): August 29, 2023

Study Registration Dates

• First Submitted: May 30, 2021
• First Submitted That Met QC Criteria: May 30, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Onchocerciasis; River blindness; Onchocerca volvulus; ABBV-4083; Tylamac
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Infections; Gastrointestinal Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Parasitic Diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Intestinal Obstruction; Filariasis; Torsion Abnormality; Onchocerciasis; Intestinal Volvulus; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Ivermectin; Albendazole
• Other Study ID Numbers: B18-894; DNDi-TYL-01 (Other Identifier: DNDi)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

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.: No