Rheumatoid Arthritis (RA)
Conditions
Keywords
Rheumatoid Arthritis (RA), T-Cell Engagers (TCEs), B-Cell Depletion
Brief summary
This is a Phase 1, open-label, first-in-human study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of KT502 administered subcutaneously to participants with Rheumatoid Arthritis (RA). The study will have 2 parts: Part A is a single ascending dose finding (SAD) and Part B is dose escalation by fractionated dosing.
Interventions
DRUGKT502
KT502 is a monoclonal antibody that depletes B cells by targeting CD19 and CD3
Sponsors
Kali Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A: Single Ascending Dose Finding (SAD) Part B: Dose escalation with fractionated dosing
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: 1. 18 to 75 years old 2. Diagnosis of adult-onset RA for at least 6 months 3. Moderately to severely active RA 4. Inadequate treatment response as defined in the protocol 5. RF + or ACPA+ 6. Stable use of traditional DMARDs is permitted 7. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions. Exclusion: 1. Functional class IV as defined by the ACR Classification of Functional Status in RA 2. Presence of any concomitant autoimmune disease other than RA 3. Active infection, history of serious recurrent or chronic infection 4. History of progressive multifocal leukoencephalopathy 5. Have a diagnosis or history of malignant disease within 5 years or breast cancer diagnosed within the previous 10 years. 6. History of or planned organ transplant and/or autologous or allogeneic hematopoietic stem cell transplantation 7. Receipt of live vaccine within 4 weeks 8. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after study 9. Women who are pregnant or breastfeeding 10. Significant or uncontrolled medical disease that would preclude participant participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | From Baseline Up to 12 weeks | Incidence and severity of Adverse Events, including DLTs, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 |
| Incidence of Cytokine-release Syndrome (CRS) | From Baseline Up to 12 Weeks | Incidence and severity of CRS with severity determined according to the 2019 American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus grading criteria |
| Changes in Pulse Rate from Baseline | From Baseline Up to 12 Weeks | Vital signs: Changes in Pulse Rate from Baseline |
| Changes in Respiratory Rate from Baseline | From Baseline to 12 Weeks | Vital Signs: Changes in Respiratory Rate from Baseline |
| Changes in Blood Pressure from Baseline | Baseline to 12 Weeks | Vital Signs: Changes in Blood Pressure from Baseline |
| Changes in Temperature from Baseline | Baseline to 12 Weeks | Vital Signs: Changes in Body Temperature from Baseline |
| Changes in Hematology Clinical Laboratory Results from Baseline | From Baseline Up to 12 Weeks | Hematology: Changes in results from Baseline |
| Changes in Chemistry Clinical Laboratory Results from Baseline | From Baseline Up to 12 Weeks | Chemistry: Changes in results from Baseline |
| Changes in Urinalysis Clinical Laboratory Results from Baseline | Baseline Up to 12 Weeks | Urinalysis: Changes in results from Baseline |
| Changes in Coagulation Clinical Laboratory Results from Baseline | From Baseline Up to 12 Weeks | Coagulation: Changes in results from Baseline |
| ECG | From Baseline to 12 Weeks | Change from baseline in 12-lead electrocardiogram (ECG) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentrations of KT502 | Part A: Pre-dose; Day 2, 3, 8, 15, 29 Part B (1st Dose): Pre-dose, Day 2, 3 Part B (2nd Dose): Pre-dose Day 8; Day 9, 10, 11, 15, 29, 43, 57 and 85 | Blood samples will be collected at specific time points for calculating serum concentrations of KT502 |
| Incidence of Treatment-induced Anti-Drug Antibodies (ADAs) | Part A: Pre-dose; Day 8, 15, 22, 29, 43, 57 and 85 Part B (1st Dose): Pre-dose Part B (2nd Dose): Pre-dose Day 8; Day 11, 15, 22, 29, 43, 57 and 85 | Immunogenicity: Incidence of participants with treatment induced Anti-Drug Antibodies (ADA) |
| To Determine Cmax | Day 1 - Day 85 | Maximum observed serum KT502 concentration |
| To Determine Tmax, Derived from Serum Concentration of each Dose of KT502 | Day 1 - Day 85 | Time to maximum observed concentration |
| Area Under the Serum-concentration Time Curve (AUC) from Time Zero to the Last Timepoint with Measurable Analyte Concentration (AUC0-t) | Day 1 - Day 85 | Area under the concentration-time curve from 0 to the time of the last quantifiable concentration (AUClast) |
| AUC from Time Zero to Infinity (AUCinf) | Day 1 - Day 85 | Area under the plasma concentration versus time curve (AUC) from time 0 extrapolated to infinity |
| To Determine Terminal Half-Life (T1/2) | Day 1 - Day 85 | Terminal elimination half-life summarized by dosing regimen |
| Total Body Clearance (CL/F) | Day 1 - Day 85 | CL is the measure of the rate at which a drug is metabolized or eliminated by normal biological processes |
| Volume of Distribution During the Terminal Phase (Vz/F) | Day 1 - Day 85 | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug |
| Change in Levels of B Cell Count | Screening; Day 1 - Day 85 | Pharmacodynamics: Change in levels of B cell counts measured at specific timepoints |
| Duration of B Cell Depletion | Day 1 - Day 85 | Pharmacodynamics: The duration of B cell depletion measured from Baseline |
| Change in Levels of Acute Inflammatory Markers | Pre-dose; Day 2, 3, 4, 5, 8, 9, 10, 15, 22, 29, 43, 57 and 85 | Pharmacodynamics: Change in levels of acute Inflammatory markers (C-reactive protein (CRP) and CRS-related cytokines at specific timepoints |
Countries
Australia, New Zealand
Contacts
CONTACTTrial Information
Outcome results
None listed