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

A Phase 1a, Open-Label, First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KT501 by a Single Subcutaneous Administration in Participants With Rheumatoid Arthritis

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).

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: KT501

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Information; Phone Number: 1-858-888-3080; Email: clinical@kalitherapeutics.com

Study Locations

• Australia
  • Bayswater, Australia
    • Recruiting
    • Kali Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; KT501 Subcutaneous Injection Dose Level 1	Drug: KT501; KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.
Experimental: Dose Level 2; KT501 Subcutaneous Injection Dose Level 2	Drug: KT501; KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.
Experimental: Dose Level 3; KT501 Subcutaneous Injection Dose Level 3	Drug: KT501; KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.
Experimental: Dose Level 4; KT501 Subcutaneous Injection Dose Level 4	Drug: KT501; KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.
Experimental: Dose Level 5; KT501 Subcutaneous Injection Dose Level 5	Drug: KT501; KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	From Baseline Up to 12 Weeks
Changes in Pulse Rate from Baseline	Vital signs: Changes in Pulse Rate from Baseline	From Baseline Up to 12 Weeks
Changes in Respiratory Rate from Baseline	Vital Signs: Changes in Respiratory Rate from Baseline	From Baseline to 12 Weeks
Changes in Blood Pressure from Baseline	Vital Signs: Changes in Blood Pressure from Baseline	From Baseline Up to Week 12
Changes in Temperature from Baseline	Vital Signs: Changes in Body Temperature from Baseline	From Baseline to 12 Weeks
Changes in Hematology Clinical Laboratory Results from Baseline	Hematology: Changes in results from Baseline	From Baseline Up to 12 Weeks
Changes in Chemistry Clinical Laboratory Results from Baseline	Chemistry: Changes in results from Baseline	From Baseline Up to 12 Weeks
Changes in Urinalysis Clinical Laboratory Results from Baseline	Urinalysis: Changes in results from Baseline	From Baseline Up to 12 Weeks
Changes in Coagulation Clinical Laboratory Results from Baseline	Coagulation: Changes in results from Baseline	From Baseline Up to 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentrations of KT501	Blood samples will be collected at specific time points for calculating 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.
Incidence of Treatment-induced Anti-Drug Antibodies (ADAs)	For Immunogenicity: Incidence of participants with treatment induced Anti-Drug Antibodies (ADA)	Pre-dose and on Day 1; Day 8, 11, 15, 22, 29, 43, 57 and 85.
To Determine Cmax	Maximum observed serum KT501 concentration	Day 1 - Day 85
To Determine Tmax, Derived from Serum Concentration of each Dose of KT501	Time to maximum observed concentration	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)	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	Day 1 - Day 85
To Determine Terminal Half-Life (T1/2)	Terminal elimination half life summarized by dosing regimen	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	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.	Day 1 - Day 85
Change in Levels of B Cell Count	Pharmacodynamics: Change in levels of B cell counts measured at specific timepoints	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	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	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	From Baseline to 12 Weeks

Collaborators and Investigators

• Sponsor: Kali Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 6, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis (RA); Autoimmune; T-cell Engagers (TCEs); B-cell Depletion
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: KT501-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a Phase 1 trial.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No