Rheumatoid Arthritis (RA)
Conditions
Keywords
Rheumatoid Arthritis (RA), Autoimmune, 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 KT501 administered subcutaneously to participants with Rheumatoid Arthritis (RA).
Detailed description
This is a Phase 1, open-label, first-in-human dose escalation study to investigate the safety, tolerability, pharmacokinetic and pharmacodynamic of KT501 by a single subcutaneous administration in participants with Rheumatoid Arthritis (RA). Up to a total of 5 cohorts with up to approximately 24 participants in total with RA will be enrolled. All participants will receive a single dose of KT501 on Day 1 and followed up until Week 12. For any participants with B cells lower than baseline level or lower limit quantification, whichever is lower, additional B cell follow up is required up to Week 48 after the study treatment.
Interventions
DRUGKT501
KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.
Sponsors
Kali Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Ascending Dose (SAD)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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 criteria
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 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 | From Baseline Up to Week 12 | Vital Signs: Changes in Blood Pressure from Baseline |
| Changes in Temperature from Baseline | From 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 | From 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 |
| Incidence of Adverse Events | From Baseline Up to 12 weeks | Incidence and severity of Adverse Events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 15, 22, 29,, 57 and 85. | Pharmacodynamics: Change in levels of acute Inflammatory markers (C-reactive protein (CRP) and CRS-related cytokines at specific timepoints |
| 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 |
| Changes in Blood Pressure from Baseline | From Baseline to 12 Weeks | Vital Signs: Changes in Blood Pressure from Baseline |
| To Determine Terminal Half-Life (T1/2) | Day 1 - Day 85 | Terminal elimination half life summarized by dosing regimen |
| Serum Concentrations of KT501 | Pre-dose and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85. | Blood samples will be collected at specific time points for calculating serum concentrations of KT501 |
| Incidence of Treatment-induced Anti-Drug Antibodies (ADAs) | Pre-dose and on Day 1; Day 8, 11, 15, 22, 29, 43, 57 and 85. | For Immunogenicity: Incidence of participants with treatment induced Anti-Drug Antibodies (ADA) |
| To Determine Cmax | Day 1 - Day 85 | Maximum observed serum KT501 concentration |
| To Determine Tmax, Derived from Serum Concentration of each Dose of KT501 | 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) |
| 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 | Pre-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85. | Pharmacodynamics: Change in levels of B cell counts measured at specific timepoints |
Countries
Australia
Contacts
CONTACTTrial Information
Outcome results
None listed