Healthy Volunteers, Rheumatoid Arthritis
Conditions
Keywords
Healthy Volunteers, Healthy Subjects, Healthy Participants, Patients, Rheumatoid Arthritis, RA
Brief summary
This double-blind, randomized, placebo-controlled study will assess the safety and pharmacokinetics of ZB002 in healthy participants and in participants with rheumatoid arthritis (RA). The study consists of 2 parts. Part A: Single Ascending Dose (SAD), which will include only healthy volunteers. Part B: Multiple Ascending Dose (MAD), will commence after completion of the SAD study and will include RA participants.
Detailed description
Part A (SAD): Up to approximately 48 healthy volunteers across 6 cohorts randomized to receive ZB002 or placebo as a single dose. Part B (MAD): Up to approximately 24 participants with RA across 3 cohorts randomized to receive ZB002 or placebo as multiple doses.
Interventions
DRUGZB002
ZB002 will be administered subcutaneously as per schedule specified in the respective arm.
DRUGPlacebo
Placebo will be administered subcutaneously as per schedule specified in the respective arm.
Sponsors
Zenas BioPharma (USA), LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria Part A SAD (HV): * Healthy male or female participants 18 to 55 years of age. * Body weight ≥ 50 kg for male participants and ≥ 45 kg for female participants; body mass index of 18 to 35 kg/m\^2 for both male and female participants. * Considered in good health as determined by the Investigator. * Female participants of child-bearing potential must agree to abstinence or use an effective form of contraception. * Male participants must be surgically sterile or agree to use effective contraception. * Willing and able to understand the characteristics and purposes of the study, including possible risks involved, and willing to comply with all the study requirements and provide written informed consent for the study. Part B MAD (RA Participants): * Male or female participants 18 to 70 years (inclusive) of age at Screening. * Body mass index of ≥ 18.0 and ≤ 40.0 kg/m2. * Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for RA ≥ 3 months before Screening. * Use of methotrexate at 7.5 to 25 mg/week for ≥ 3 months, with stable dosing for ≥ 4 weeks, before randomization. Hydroxychloroquine/chloroquine and/or sulfasalazine are allowed if started ≥ 3 months before randomization and a stable dose is maintained after the Screening Visit. Main
Exclusion criteria
Part A SAD (HV): * Surgery within 4 weeks before Screening or planned surgery during the clinical study. * Use of prescription medications, biological products, or other medicines within 2 weeks before Study Day 1 or 5 half-lives of the product, whichever is greater. Use of over-the-counter medications or vitamins/dietary supplements within 7 days of dosing unless considered by the Investigator to not pose a risk or impact the study results. * Treatment with any investigational drug within 30 days or 5 half-lives, whichever is greater, before the first dose of the study drug, or currently enrolled in another clinical study. * Clinically significant ECG abnormality. * Positive for HIV infection, active hepatitis C, or hepatitis B. * Positive for COVID-19 virus. * Positive QuantiFERON®-TB Gold or T-SPOT® test for Mycobacterium tuberculosis. * Bacteria, viruses, systemic fungi, parasites, or other opportunistic infections within 30 days before Study Day 1. * Documented history of drug abuse in the previous 12 months before Screening, or positive for urine drug screen on Screening and/or Day -1. * Donated blood (including component blood) or lost \> 400 mL within 3 months before Screening or received a transfusion within 3 months of Screening. * History of relevant allergies (including allergy to any murine or human-derived protein or immunoglobulin products, rubber or latex, or other allergies that in the opinion of the Investigator make inclusion in the study inappropriate). * Average daily smoking \> 10 cigarettes or cigarette equivalents per day within 6 months of Screening. * Consume \> 14 standard units of alcohol per week (1 standard unit is equivalent to approximately 360 mL of beer, 45 mL of spirits with 40% alcohol, or 150 mL of wine) or a positive alcohol breath test on Day -1. Part B MAD (RA Participants): * Inflammatory joint disease other than RA. Note: Current diagnosis of secondary Sjogren's Syndrome is permitted. * Surgery within 4 weeks before Screening or planned surgery during the clinical study. * History of any malignancy within 5 years, except for successfully treated nonmelanoma skin cancer or localized carcinoma in situ of the cervix. * Documented history of drug abuse in the previous 12 months before Screening (Days -28 to -1), or positive for urine drug screen for nonprescribed drugs other than cannabinoid at Screening. * Any condition considered by the investigator to make participation in the study inappropriate. * Donated blood (including component blood) or lost \> 400 mL within 1 month before Screening or received a transfusion within 3 months of Screening. * After the Screening Visit, corticosteroid use \> 10 mg/day (prednisone equivalent) or increase in dose * Positive for HIV infection, active hepatitis C, or hepatitis B. * Test positive for Mycobacterium tuberculosis. * Bacterial, viral, systemic fungal, parasitic, or opportunistic infection not resolved at least 14 days before Study Day 1 or expected to be treated with antibiotics during the Treatment Period, or history of recurrent infections. * Employees or related personnel of the study site, the sponsor, or contract research organization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Safety and Tolerability of multiple doses of ZB002 in participants with RA | Day 1 through Day 176 | To evaluate the safety and tolerability of ZB002 in participants with RA by assessing the number of participants with Treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAE leading to discontinuation |
| Part A: Safety and Tolerability in HVs | Day 1 through Day 120 | To evaluate the safety and tolerability of ZB002 in HVs by assessing the number, severity and type of adverse events, including changes in laboratory safety test and electrocardiogram (ECG) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B (Dose 3 only): AUC from time 0 to the last quantifiable concentration (AUClast) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Dose 3 only): Apparent clearance following extravascular dosing (CL/F) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Dose 3 only): Apparent volume of distribution following extravascular (Vz/F) | Day 1 through Day 176 | Pharmacokinetics |
| Part B: Serum anti-ZB002 antibody prevalence and incidence | Day 1 through Day 176 | — |
| Part B: Cytokine/chemokine secretion in ex vivo stimulated whole blood | Day 1 through Day 176 | Pharmacodynamic |
| Part A: Maximum observed serum concentration (Cmax) | Day 1 through Day 120 | Pharmacokinetics |
| Part A: Time for Cmax (Tmax) | Day 1 through Day 120 | Pharmacokinetics |
| Part A: Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) | Day 1 through Day 120 | Pharmacokinetics |
| Part A: AUC from time 0 to the last quantifiable concentration (AUClast) | Day 1 through Day 120 | Pharmacokinetics |
| Part A: Terminal half-life (t1/2) | Day 1 through Day 120 | Pharmacokinetics |
| Part A: Apparent clearance following extravascular dosing (CL/F) | Day 1 through Day 120 | Pharmacokinetics |
| Part A: Apparent volume of distribution following extravascular administration (Vz/F) | Day 1 through Day 120 | Pharmacokinetics |
| Part B (All Doses): Serum trough concentration (Ctrough) | Day 1 through Day 176 | Before repeat-dose administration (or at the end of the dosing interval \[tau\] after the final dose) |
| Part B (Doses 1 and 3): Maximum observed serum concentration (Cmax) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Doses 1 and 3): Time for Cmax (Tmax) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Doses 1 and 3): AUC over the dosing interval, tau (AUCtau) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Doses 1 and 3): Accumulation ratio of Cmax (ARCmax) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Dose 3 only): Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Doses 1 and 3): Accumulation ratio of AUC (ARAUC) | Day 1 through Day 176 | Pharmacokinetics |
| Part B (Dose 3 only): Terminal half-life (t1/2) | Day 1 through Day 176 | Pharmacokinetics |
Countries
Australia, New Zealand
Outcome results
None listed