A Study of Orally Administered JNJ-440 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses Including Food Effect Evaluation; After Multi-Day Dosing in Healthy Participants; and After Multiple (Ascending) Doses in Participants With Chronic Hepatitis B

Alios Biopharma

Status and phase: Completed; Phase 1

Conditions: Chronic Hepatitis B

Treatments: Drug: JNJ-440; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03439488

2017-004657-17 (EudraCT Number)

JNJ-440-1301 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of JNJ-440 in healthy and Chronic Hepatitis B (CHB) participants after single and multiple doses; and to evaluate the pharmacokinetic (PK) of JNJ-440 in healthy participants and in CHB participants following single and multiple dose regimens, administered alone (healthy participants and CHB participants).

Enrollment: 130 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Inclusion Criteria for Healthy Participants:

• Female participants (except for postmenopausal women) must have a negative pregnancy test at screening and on Day -1
• Participants must have a body mass index (BMI; weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 30.0 kilogram per meter square (kg/m^2), extremes included
• Participants must agree not to donate blood during the study and for at least 1 month after the completion of study drug administration

Inclusion Criteria for Participants with Chronic Hepatitis B (CHB):

• Participant must have CHB infection documented by: (a) Serum hepatitis B surface antigen (HBsAg) positive at screening and at least 6 months prior to screening; (b) Serum antibody immunoglobulin M (IgM) anti-HBc antibody negative at screening
• Participants must currently not be receiving any CHB treatment at screening, that is, have never received treatment with hepatitis B virus (HBV) antiviral medicines, nucleos(t)ide analog (NAs), interferon (IFN) products, or investigational anti-HBV agents, OR Have not been on treatment with HBV antiviral medicines, NAs, or IFN products within 6 months prior to baseline (first intake of study drugs)

Exclusion criteria

Exclusion Criteria for Healthy Participants:

• Participants with a past history of cardiac arrhythmias (example, extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (example, hypokalemia, family history of long QT Syndrome) or history or other clinical evidence of significant or unstable cardiac disease (example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant electrocardiogram [ECG] abnormalities), moderate to severe valvular disease or uncontrolled hypertension at screening. Any evidence of heart block or bundle branch block is also exclusionary
• Participants with any history of confirmed clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticarial
• Participants with a history of confirmed clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy witnessed in previous studies with experimental drugs

Exclusion Criteria for Participants with CHB:

• Participant with positivity of anti-HBs antibodies
• Participants with current hepatitis D virus (HDV) infection (confirmed by HDV antibody) at screening

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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130 participants in 3 patient groups

Part 1 (Healthy Participants): Single Ascending Dose (SAD)

Experimental group

Description:

Participants in Cohorts 1 to 5 and 3 optional cohorts (Cohorts 6, 7 and 10) will receive a single dose of JNJ-440/placebo on Day 1. Two cohorts will receive a second dose of JNJ-440/placebo in a fed state (participants from Cohort 3 will also participate in Cohort 8) or as an alternative JNJ-440 formulation (participants from Cohort 2 will also participate in optional Cohort 9) after a washout window of at least 10 days. In Cohorts 1 to 4, study drug will be administered under fasted conditions; in the remaining cohorts, study drug will be administered under fasted/fed conditions depending on the results of the food effect evaluation.

Treatment:

Drug: Placebo

Drug: JNJ-440

Part 2 (Healthy Participants): Multiple Ascending Dose (MAD)

Experimental group

Description:

Participants in Cohorts 1 and 2 will receive a once daily dose of JNJ-440/placebo for the duration of 7 days under fasted or fed conditions. Participants in an optional cohort (Cohort 3) may receive a once daily or twice daily dose of JNJ-440/placebo for the duration of 7 or 14 days under fasted or fed conditions. The starting dose for Cohort 1 in Part 2 will be determined by the Sponsor in consultation with the Principal Investigator based on the data from Part 1. Dose escalation will be performed only after review of safety and pharmacokinetic (PK) data after a minimum of 7 days of study drug administration.

Treatment:

Drug: Placebo

Drug: JNJ-440

Part 3 (Chronic Hepatitis B [CHB] Participants): MAD

Experimental group

Description:

Participants in Cohorts 1 and 2 and 3 optional cohorts (Cohorts 3, 4, and 5) will receive multiple ascending doses of JNJ-440/placebo once daily or twice daily for 28 days under fed or fasted conditions. The starting dose and formulation for Cohort 1 will be determined based on the review of available data in healthy participants from Part 1 (SAD) and Part 2 (MAD). Dose escalation will be performed only after review of safety, tolerability, and PK data after a minimum of 14 days of study drug administration from at least 8 CHB participants.

Treatment:

Drug: Placebo

Drug: JNJ-440