AB-101 in Combination With B-Cell Depleting mAb in Patients Who Failed Treatment for Class III or IV Lupus Nephritis

A Phase 1 Study to Evaluate the Efficacy and Safety of AB-101, an Allogeneic Cord Blood- Derived NK-Cell Therapy in Combination With B-Cell Depleting mAb in Patients Who Failed Treatment for Class III or IV Lupus Nephritis

AB-101 (also known as AlloNK) is an off-the shelf, allogeneic cell product made of "natural killer" cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that is known to enhance the effect of monoclonal antibody therapies.

This clinical trial will enroll adult patients with lupus nephritis Class III or IV either with or without the presence of Class V who relapsed or did not respond to previous standard of care treatment approaches.

The primary objective is to assess the safety, tolerability and preliminary activity of AB-101 plus rituximab after cyclophosphamide and fludarabine in adult subjects with relapsed/refractory lupus nephritis Class III or IV, with or without the presence of Class V.

Patients will be assigned to receive either AB-101 alone as monotherapy or in combination with rituximab. All patients will receive at least 1 treatment cycle of AB-101, followed by scheduled assessments of overall health and response status.

Patients may receive up to 2 cycles of treatment spaced 24 weeks apart.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis - WHO Class IV; Lupus Nephritis - WHO Class III
• Intervention / Treatment: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: AB-101

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AB-101-03 Study Team; Phone Number: 858-377-8306; Email: AB-101-03StudyTeam@ArtivaBio.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92121
      • Recruiting
      • University of California, San Diego
      • Contact: Bosco Trinh
      • Principal Investigator: Bethany Karl, DO

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult subjects with biopsy proven lupus nephritis Class III or IV either with or without the presence of Class V according to the 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, who failed or did not respond to previous standard of care treatment approaches
• A kidney biopsy must be performed < 24 weeks prior to the screening visit or during the screening period.
• Eligible subjects must have evidence of active disease on renal biopsy based on the modified NIH Lupus Nephritis activity and chronicity indices.
• Eligible subjects must have detectable anti-double stranded DNA antibody titers for enrollment.

Exclusion Criteria:

• Known past or current malignancy other than inclusion diagnosis
• Known clinically significant cardiac disease
• Known past or current clinically significant lung disease, including:
• Current use of tobacco products
• Subjects with a history of HBV infections are considered ineligible

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose confirmation of AB-101 as Monotherapy	Drug: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-101; NK Cell Therapy
Experimental: Phase 1: Dose confirmation of AB-101 plus Rituximab combination	Drug: Rituximab; Anti-CD20 antibody therapy; Drug: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-101; NK Cell Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events	Incidence, severity and causality of adverse events and serious adverse events	From the time of consent through 104 weeks after initiation of study treatment
AB-101 Clinical Activity	Determined by Overall Renal Response Rate	From the time of first dose through 104 weeks after initiation of study treatment

Collaborators and Investigators

• Sponsor: Artiva Biotherapeutics, Inc.
• Investigators: Study Director: Sudhir Borgonha, MD, Artiva Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): February 24, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine
• Other Study ID Numbers: AB-101-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No