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

NCT04913610 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: B18-894DNDi-TYL-01
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 2

Brief Summary

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 receive the most effective treatment combination(s) 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.

Conditions

Onchocerciasis

Keywords

Onchocerciasis; Onchocerca volvulus; River blindness; ABBV-4083; Tylamac

Outcome Measures

Primary Outcomes (1)

• Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules

  The Wolbachia endobacteria status of each live female adult worm was determined by immunohistology of nodules collected after nodulectomy at the Month 6 visit.

  At Month 6

Secondary Outcomes (8)

• Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6

  At Month 6

• Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6

  At Month 6

• Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6

  At Month 6

• Part 1: Percentage of Participants Without Skin Microfilariae at Month 3

  At Month 3

• Part 1: Percentage of Participants Without Skin Microfilariae at Month 6

  At Month 6

Study Arms (5)

Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days

EXPERIMENTAL

Participants received ABBV-4083 400 mg administered orally as capsules plus placebo capsules for albendazole for 7 days followed by placebo capsules for ABBV-4083 for 7 days.

Drug: ABBV-4083; Drug: Placebo for ABBV-4083; Drug: Placebo for Albendazole

Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days

EXPERIMENTAL

Participants received ABBV-4083 400 mg administered orally as capsules plus placebo capsules for albendazole for 7 days followed by ABBV-4083 400 mg administered orally as capsules for 7 days.

Drug: ABBV-4083; Drug: Placebo for Albendazole

Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days

EXPERIMENTAL

Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 7 days followed by placebo capsules for ABBV-4083 for 7 days.

Drug: ABBV-4083; Drug: Placebo for ABBV-4083; Drug: Albendazole

Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d

EXPERIMENTAL

Participants received ABBV-4083 400 mg administered orally as capsules plus albendazole 400 mg capsules for 3 days followed by ABBV-4083 400 mg and placebo capsules for albendazole for 4 days followed by placebo capsules for ABBV-4083 for 7 days.

Drug: ABBV-4083; Drug: Placebo for ABBV-4083; Drug: Albendazole; Drug: Placebo for Albendazole

Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days

EXPERIMENTAL

Participants received placebo for ABBV-4083 administered orally as capsules plus albendazole 400 mg capsules for 7 days followed by placebo capsules for ABBV-4083 for 7 days.

Drug: Placebo for ABBV-4083; Drug: Albendazole

Interventions

ABBV-4083 DRUG

Oral Capsule

Also known as: Tylamac

Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days; Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d

Placebo for ABBV-4083 DRUG

Oral Capsule

Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d

Albendazole DRUG

Oral encapsulated tablets

Also known as: Zentel

Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d

Placebo for Albendazole DRUG

Oral Capsule

Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days; Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days; Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Clinically significant abnormal physical and/or neurological 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 within 48 hours and/or use of drugs of abuse within 15 days before IMP administration.

Sponsors & Collaborators

• AbbVie: lead
• Drugs for Neglected Diseases: collaborator

Study Sites (2)

Hôpital Général de Référence de Kimpese

Kimpese, Bas-Congo Province, Democratic Republic of the Congo

Location

Hôpital Général de Référence de Masi-Manimba

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Location

MeSH Terms

Conditions

Onchocerciasis; Onchocerciasis, Ocular

Interventions

Albendazole

Condition Hierarchy (Ancestors)

Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Eye Infections, Parasitic; Vector Borne Diseases; Eye Infections; Eye Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Clinical Trial Data
• Organization: Drugs for Neglected Diseases initiative

ctdata@dndi.org

41 22 906 9230

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2021
• First Posted: June 4, 2021
• Study Start: May 22, 2021
• Primary Completion: August 29, 2023
• Study Completion: August 29, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)