First-in-human KT501 for rheumatoid arthritis

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 Phase 1, open-label test will give a single under-the-skin dose of KT501 to adults with moderate to severe rheumatoid arthritis to see if it is safe and how it acts in the body.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Kali Therapeutics, Inc. (Industry-sponsored)
• Locations: 1 site (Bayswater)
• Trial ID: NCT07234773 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label, first-in-human dose-escalation trial of a single subcutaneous administration of KT501 in people with rheumatoid arthritis. Up to five dose cohorts will enroll approximately 24 participants in total, with all participants dosed on Day 1 and followed for safety, pharmacokinetics (PK), and pharmacodynamics (PD). Primary outcomes focus on safety and tolerability, with PK/PD sampling to characterize how the drug is processed and its biological effects, including B-cell changes. Most participants are followed to Week 12, with extended B-cell monitoring to Week 48 for those with lowered B-cell counts.

Who should consider this trial

Good fit: Adults 18–75 with adult-onset RA for at least 6 months, moderately to severely active disease, RF+ or ACPA+, who have had inadequate response to prior therapy and can attend study visits and remain on stable DMARDs are ideal candidates.

Not a fit: Patients with ACR functional class IV, other concomitant autoimmune diseases, active or recurrent serious infections, recent malignancy, organ transplant history, recent live vaccination, or recent major surgery are excluded and unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, KT501 could provide a new targeted way to reduce B cells and lower disease activity with a single subcutaneous dose.

How similar studies have performed: B-cell depletion therapies such as rituximab have proven effective in RA, but first-in-human T-cell engager approaches like KT501 are novel and have not yet been tested in patients.

Eligibility criteria

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

Where this trial is running

Bayswater

• Kali Study Site — Bayswater, Australia (Recruiting)

Study contacts

• Study coordinator: Trial Information

Conditions Rheumatoid Arthritis; Autoimmune; T-cell Engagers; B-cell Depletion