Onchocerciasis
Conditions
Keywords
Onchocerciasis, Onchocerca volvulus, River blindness, ABBV-4083, Tylamac
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.
Detailed description
The study was terminated at the conclusion of Part 1, and Part 2 of the study was not conducted.
Interventions
DRUGABBV-4083
Oral Capsule
DRUGPlacebo for ABBV-4083
Oral Capsule
DRUGAlbendazole
Oral encapsulated tablets
DRUGPlacebo for Albendazole
Oral Capsule
Sponsors
Drugs for Neglected Diseases
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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: * 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. * 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules | At Month 6 | The Wolbachia endobacteria status of each live female adult worm was determined by immunohistology of nodules collected after nodulectomy at the Month 6 visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6 | At Month 6 | The percentage of live female adult worms out of all female adult worms per participant was determined after nodulectomy at the Month 6 visit. |
| Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6 | At Month 6 | The absence of microfilariae in nodular tissue per participant was determined after nodulectomy at the Month 6 visit. |
| Part 1: Percentage of Participants Without Skin Microfilariae at Month 3 | At Month 3 | The presence or absence of microfilariae in skin was determined at the Month 3 visit. |
| Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6 | At Month 6 | The percentage of live female adult worms with only degenerated embryos in the uterus per participant was determined after nodulectomy at the Month 6 visit. |
| Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3 | Baseline, Month 3 | Skin microfilarial density is defined as the mean number of microfilariae/mg of skin per participant. |
| Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6 | Baseline, Month 6 | Skin microfilarial density is defined as the mean number of microfilariae/mg of skin per participant. |
| Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6 | At Month 6 | The Wolbachia endobacteria status of each live female adult worm was determined by PCR of nodules collected after nodulectomy at the Month 6 visit. |
| Part 1: Percentage of Participants Without Skin Microfilariae at Month 6 | At Month 6 | The presence or absence of microfilariae in skin was determined at the Month 6 visit. |
Countries
Democratic Republic of the Congo
Participant flow
Pre-assignment details
A total of 153 participants were randomized, of which 151 received study drug (Intention-to-Treat, ITT; Safety population).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days 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. | 31 |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days 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. | 31 |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days 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. | 29 |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d 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. | 29 |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days 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. | 31 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Randomized Participants | Did Not Receive Treatment | 0 | 0 | 1 | 1 | 0 |
| Treated (ITT & Safety Population) | Lost to Follow-up | 1 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Total | 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 | 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 |
|---|---|---|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 10.36 | 39.6 years STANDARD_DEVIATION 11.55 | 38.5 years STANDARD_DEVIATION 12.34 | 38.7 years STANDARD_DEVIATION 10.78 | 40.1 years STANDARD_DEVIATION 12.08 | 37.1 years STANDARD_DEVIATION 11.73 |
| Body weight | 53.55 kilograms STANDARD_DEVIATION 7.03 | 52.01 kilograms STANDARD_DEVIATION 6.8 | 49.77 kilograms STANDARD_DEVIATION 6.96 | 52.38 kilograms STANDARD_DEVIATION 6.42 | 53.48 kilograms STANDARD_DEVIATION 7.12 | 50.98 kilograms STANDARD_DEVIATION 6.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants | — | — | — | — |
| Number of operable sites with onchocercomata | 1.5 sites STANDARD_DEVIATION 0.72 | 1.5 sites STANDARD_DEVIATION 0.76 | 1.5 sites STANDARD_DEVIATION 0.68 | 1.6 sites STANDARD_DEVIATION 1.02 | 1.6 sites STANDARD_DEVIATION 0.74 | 1.6 sites STANDARD_DEVIATION 0.67 |
| Number of palpated onchocerca nodules | 1.7 nodules STANDARD_DEVIATION 0.83 | 1.7 nodules STANDARD_DEVIATION 0.92 | 1.7 nodules STANDARD_DEVIATION 0.93 | 1.8 nodules STANDARD_DEVIATION 1.15 | 1.7 nodules STANDARD_DEVIATION 1.03 | 1.7 nodules STANDARD_DEVIATION 0.7 |
| Number of previous ivermectin rounds | 0.4 rounds STANDARD_DEVIATION 0.71 | 0.3 rounds STANDARD_DEVIATION 0.65 | 0.2 rounds STANDARD_DEVIATION 0.67 | 0.3 rounds STANDARD_DEVIATION 0.59 | 0.4 rounds STANDARD_DEVIATION 0.87 | 0.0 rounds STANDARD_DEVIATION 0.18 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 151 Participants | 31 Participants | 29 Participants | 29 Participants | 31 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 16 Participants | 6 Participants | 4 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 29 Participants | 135 Participants | 25 Participants | 25 Participants | 29 Participants | 27 Participants |
| Skin microfilarial density | 8.22 mf/mg of skin STANDARD_DEVIATION 12.25 | 18.23 mf/mg of skin STANDARD_DEVIATION 29.71 | 16.59 mf/mg of skin STANDARD_DEVIATION 25.81 | 19.45 mf/mg of skin STANDARD_DEVIATION 34.97 | 20.60 mf/mg of skin STANDARD_DEVIATION 35.52 | 26.55 mf/mg of skin STANDARD_DEVIATION 33.06 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 | 0 / 30 | 0 / 30 | 0 / 122 | 0 / 31 |
| other Total, other adverse events | 14 / 31 | 9 / 31 | 13 / 30 | 10 / 30 | 46 / 122 | 14 / 31 |
| serious Total, serious adverse events | 0 / 31 | 2 / 31 | 2 / 30 | 0 / 30 | 4 / 122 | 4 / 31 |
Outcome results
Primary
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.
Time frame: At Month 6
Population: Per protocol population: all ITT participants who had nodulectomy at Month 6 (ND6M) with live female adult worms, who completed treatment, and who did not take prohibited medication(s) during the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules | 6.0 Percentage of worms without Wolbachia |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules | 2.3 Percentage of worms without Wolbachia |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules | 0.0 Percentage of worms without Wolbachia |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules | 0.0 Percentage of worms without Wolbachia |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms Without Wolbachia at Month 6 as Assessed By Immunohistology of Nodules | 2.6 Percentage of worms without Wolbachia |
Secondary
Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3
Skin microfilarial density is defined as the mean number of microfilariae/mg of skin per participant.
Time frame: Baseline, Month 3
Population: Intention-to-treat (ITT) population who had values at Baseline and Month 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3 | -0.44 Mean number of microfilariae/mg of skin | Standard Deviation 5.576 |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3 | -7.99 Mean number of microfilariae/mg of skin | Standard Deviation 16.18 |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3 | 2.43 Mean number of microfilariae/mg of skin | Standard Deviation 13.148 |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3 | 1.36 Mean number of microfilariae/mg of skin | Standard Deviation 12.189 |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 3 | -1.03 Mean number of microfilariae/mg of skin | Standard Deviation 10.787 |
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days (Arm A) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.619Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days (Arm B) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.194Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm C) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.518Mann-Whitney U test
Comparison: Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d (Arm D) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.652Mann-Whitney U test
Secondary
Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6
Skin microfilarial density is defined as the mean number of microfilariae/mg of skin per participant.
Time frame: Baseline, Month 6
Population: Intention-to-treat (ITT) population who had values at Baseline and Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6 | -0.19 Mean number of microfilariae/mg of skin | Standard Deviation 6.33 |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6 | 5.55 Mean number of microfilariae/mg of skin | Standard Deviation 24.293 |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6 | -1.19 Mean number of microfilariae/mg of skin | Standard Deviation 32.856 |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6 | -2.72 Mean number of microfilariae/mg of skin | Standard Deviation 19.769 |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Mean Within-Participant Change From Baseline in Skin Microfilarial Density at Month 6 | -1.67 Mean number of microfilariae/mg of skin | Standard Deviation 14.223 |
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days (Arm A) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.386Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days (Arm B) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.279Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm C) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.385Mann-Whitney U test
Comparison: Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d (Arm D) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.755Mann-Whitney U test
Secondary
Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6
The percentage of live female adult worms out of all female adult worms per participant was determined after nodulectomy at the Month 6 visit.
Time frame: At Month 6
Population: Intention-to-treat (ITT) population who had female adult worms
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6 | 84.27 Percentage of worms per participant | Standard Deviation 19.904 |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6 | 77.74 Percentage of worms per participant | Standard Deviation 32.445 |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6 | 78.03 Percentage of worms per participant | Standard Deviation 29.811 |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6 | 79.37 Percentage of worms per participant | Standard Deviation 27.013 |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms Out of All Female Adult Worms Per Participant at Month 6 | 79.52 Percentage of worms per participant | Standard Deviation 30.496 |
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days (Arm A) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.869Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days (Arm B) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.973Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm C) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.744Mann-Whitney U test
Comparison: Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d (Arm D) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.794Mann-Whitney U test
Secondary
Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6
The percentage of live female adult worms with only degenerated embryos in the uterus per participant was determined after nodulectomy at the Month 6 visit.
Time frame: At Month 6
Population: Intention-to-treat (ITT) population who had live female adult worms that contained either normal embryos, degenerated embryos, or both
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6 | 0.48 Percentage of worms per participant | Standard Deviation 2.086 |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6 | 7.67 Percentage of worms per participant | Standard Deviation 18.42 |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6 | 9.82 Percentage of worms per participant | Standard Deviation 19.578 |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6 | 7.59 Percentage of worms per participant | Standard Deviation 23.813 |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Live Female Adult Worms With Only Degenerated Embryos in the Uterus Per Participant at Month 6 | 10.16 Percentage of worms per participant | Standard Deviation 18.064 |
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days (Arm A) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.036Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days (Arm B) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.53Mann-Whitney U test
Comparison: Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm C) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.852Mann-Whitney U test
Comparison: Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d (Arm D) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.366Mann-Whitney U test
Secondary
Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6
The Wolbachia endobacteria status of each live female adult worm was determined by PCR of nodules collected after nodulectomy at the Month 6 visit.
Time frame: At Month 6
Population: Intention-to-treat (ITT) population who had live female adult worms
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6 | 0 Percentage of nodules |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6 | 0 Percentage of nodules |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6 | 0 Percentage of nodules |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6 | 0 Percentage of nodules |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Nodules That Contain at Least 1 Live Female Adult Worm Without Wolbachia Assessed by PCR at Month 6 | 0 Percentage of nodules |
Secondary
Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6
The absence of microfilariae in nodular tissue per participant was determined after nodulectomy at the Month 6 visit.
Time frame: At Month 6
Population: Intention-to-treat (ITT) population who had post-baseline values at Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6 | 22.7 Percentage of participants |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6 | 26.9 Percentage of participants |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6 | 41.7 Percentage of participants |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6 | 31.8 Percentage of participants |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Microfilariae in Nodular Tissue at Month 6 | 30.4 Percentage of participants |
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days (Arm A) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.559Chi-square test
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days (Arm B) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.786Chi-square test
Comparison: Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm C) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.423Chi-square test
Comparison: Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d (Arm D) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.92Chi-square test
Secondary
Part 1: Percentage of Participants Without Skin Microfilariae at Month 3
The presence or absence of microfilariae in skin was determined at the Month 3 visit.
Time frame: At Month 3
Population: Intention-to-treat (ITT) population who had post-baseline values at Month 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 3 | 3.2 Percentage of participants |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 3 | 3.2 Percentage of participants |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 3 | 3.6 Percentage of participants |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Percentage of Participants Without Skin Microfilariae at Month 3 | 3.6 Percentage of participants |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 3 | 3.3 Percentage of participants |
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days (Arm A) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.981Chi-square test
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days (Arm B) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.981Chi-square test
Comparison: Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm C) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.96Chi-square test
Comparison: Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d (Arm D) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.96Chi-square test
Secondary
Part 1: Percentage of Participants Without Skin Microfilariae at Month 6
The presence or absence of microfilariae in skin was determined at the Month 6 visit.
Time frame: At Month 6
Population: Intention-to-treat (ITT) population who had post-baseline values at Month 6
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 6 | 0 Percentage of participants |
| Part 1: ABBV-4083 400 mg + Albendazole Pbo for 7 Days, Then ABBV-4083 400 mg for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 6 | 0 Percentage of participants |
| Part 1: ABBV-4083 400 mg + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 6 | 0 Percentage of participants |
| Part 1: ABBV-4083/Albendazole 400 mg 3 d; ABBV-4083 400 mg/Albendazole Pbo 4 d; ABBV-4083 Pbo 7 d | Part 1: Percentage of Participants Without Skin Microfilariae at Month 6 | 0 Percentage of participants |
| Part 1: ABBV-4083 Pbo + Albendazole 400 mg for 7 Days, Then ABBV-4083 Pbo for 7 Days | Part 1: Percentage of Participants Without Skin Microfilariae at Month 6 | 7.1 Percentage of participants |
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 pbo for 7 days (Arm A) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.157Chi-square test
Comparison: Part 1: ABBV-4083 400 mg + albendazole pbo for 7 days, then ABBV-4083 400 mg for 7 days (Arm B) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.15Chi-square test
Comparison: Part 1: ABBV-4083 400 mg + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm C) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.15Chi-square test
Comparison: Part 1: ABBV-4083/albendazole 400 mg 3 d; ABBV-4083 400 mg/albendazole pbo 4 d; ABBV-4083 pbo 7 d (Arm D) versus Part 1: ABBV-4083 pbo + albendazole 400 mg for 7 days, then ABBV-4083 pbo for 7 days (Arm E)p-value: =0.173Chi-square test