A First-in-human Study of KT501 Administered Subcutaneously to Patients With Rheumatoid Arthritis (RA).

Phase 1RecruitingNCT07234773

Kali Therapeutics, Inc.24 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Rheumatoid Arthritis (RA)

Interventions

KT501DRUG

KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Kali Study Site

Bayswater, Australia

RECRUITING

Outcomes

Primary Outcomes

Incidence of Adverse Events

Incidence and severity of Adverse Events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

Time frame: From Baseline Up to 12 weeks

Incidence of Cytokine-release Syndrome (CRS)

Incidence and severity of CRS with severity determined according to the 2019 American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus grading criteria

Time frame: From Baseline Up to 12 Weeks

Changes in Pulse Rate from Baseline

Vital signs: Changes in Pulse Rate from Baseline

Time frame: From Baseline Up to 12 Weeks

Changes in Respiratory Rate from Baseline

Vital Signs: Changes in Respiratory Rate from Baseline

Time frame: From Baseline to 12 Weeks

Changes in Blood Pressure from Baseline

Vital Signs: Changes in Blood Pressure from Baseline

Time frame: From Baseline Up to Week 12

Changes in Temperature from Baseline

Vital Signs: Changes in Body Temperature from Baseline

Time frame: From Baseline to 12 Weeks

Changes in Hematology Clinical Laboratory Results from Baseline

Hematology: Changes in results from Baseline

Time frame: From Baseline Up to 12 Weeks

Changes in Chemistry Clinical Laboratory Results from Baseline

Chemistry: Changes in results from Baseline

Central Contacts

Trial Information

CONTACT

1-858-888-3080 clinical@kalitherapeutics.com

Data from ClinicalTrials.gov

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Secondary Outcomes

Serum Concentrations of KT501

Blood samples will be collected at specific time points for calculating serum concentrations of KT501

Time frame: Pre-dose and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85.

Incidence of Treatment-induced Anti-Drug Antibodies (ADAs)

For Immunogenicity: Incidence of participants with treatment induced Anti-Drug Antibodies (ADA)

Time frame: Pre-dose and on Day 1; Day 8, 11, 15, 22, 29, 43, 57 and 85.

To Determine Cmax

Maximum observed serum KT501 concentration

Time frame: Day 1 - Day 85

To Determine Tmax, Derived from Serum Concentration of each Dose of KT501

Time to maximum observed concentration

Time frame: Day 1 - Day 85

Area Under the Serum-concentration Time Curve (AUC) from Time Zero to the Last Timepoint with Measurable Analyte Concentration (AUC0-t)

Area under the concentration-time curve from 0 to the time of the last quantifiable concentration (AUClast)

Time frame: Day 1 - Day 85

AUC from Time Zero to Infinity (AUCinf)

Area under the plasma concentration versus time curve (AUC) from time 0 extrapolated to infinity

Time frame: Day 1 - Day 85

To Determine Terminal Half-Life (T1/2)

Terminal elimination half life summarized by dosing regimen

Time frame: Day 1 - Day 85

Total Body Clearance (CL/F)

CL is the measure of the rate at which a drug is metabolized or eliminated by normal biological processes

Time frame: Day 1 - Day 85

Volume of Distribution During the Terminal Phase (Vz/F)

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.

Time frame: Day 1 - Day 85

Change in Levels of B Cell Count

Pharmacodynamics: Change in levels of B cell counts measured at specific timepoints

Time frame: Pre-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85.

Duration of B Cell Depletion

Pharmacodynamics: The duration of B cell depletion measured from Baseline

Time frame: Day 1 - Day 85

Change in Levels of Acute Inflammatory Markers

Pharmacodynamics: Change in levels of acute Inflammatory markers (C-reactive protein (CRP) and CRS-related cytokines at specific timepoints

Time frame: Pre-dose and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 15, 22, 29,, 57 and 85.

Changes in Blood Pressure from Baseline

Vital Signs: Changes in Blood Pressure from Baseline

Time frame: From Baseline to 12 Weeks