AlloNK®, an Allogeneic Non-genetically Modified, Cord Blood-derived NK Cell Therapy, in Combination With Rituximab, Studied in Relapsing Forms of B-cell Dependent Rheumatologic Diseases.

Official title

An Open-label Phase 2a Study to Evaluate the Safety and Efficacy of AlloNK®, an Allogeneic Cord Blood-derived NK Cell Therapy, in Combination With Rituximab in Relapsing Forms of B-cell Dependent Rheumatologic Diseases

Overview

A Basket Trial of Refractory Rheumatoid Arthritis (RA), Sjögren's Disease (SjD), Idiopathic Inflammatory Myopathies (IIMs) and Systemic Sclerosis (SSc) subjects to evaluate the safety and efficacy of AlloNK, a non-genetically modified allogeneic NK cell, in combination with rituximab.

Detailed description

An open-label Phase 2a study to evaluate the safety and efficacy of AlloNK®, an allogeneic cord blood-derived NK cell therapy, in combination with rituximab in relapsing forms of B-cell dependent rheumatologic diseases.

AlloNK® (also known as AB-101) is a non-genetically modified, allogeneic, off-the-shelf, cryopreserved cord blood-derived NK cell therapy.

Interventions

• Drug Allogeneic NK Cells
  AlloNK, dosed after a conditioning regimen, combined with Rituximab.

Primary outcome measures

• Safety [Time frame: From enrollment until the end of treatment at Week 104.]

Secondary outcome measures (4)

• Rheumatoid Arthritis: Disease Activity Score 28 (DAS28 - ESR) [Time frame: Week 52]
• Sjögren's Disease: Improvement in Clinical EULAR Sjögren's Syndrome Disease Activity Index (ClinESSDAI) [Time frame: Week 52]
• Idiopathic Inflammatory Myopathies: Total Improvement Score (TIS) [Time frame: Week 52]
• Systemic Sclerosis: Revised Composite Response Index in Systemic Sclerosis (rCRISS) [Time frame: Week 52]

Eligibility criteria

For Subjects with Refractory Rheumatoid Arthritis (RA):

• Documented diagnosis of RA, meeting the 2010 ACR/EULAR classification criteria.
• Rheumatoid Factor (RF) or Anti Citrullinated Protein Antibody (ACPA) positive.
• High-sensitivity C-reactive protein (hs-CRP) > 3 mg/L or Erythrocyte Sedimentation Rate (ESR) > 28 mm/hr.
• Have had prior treatment for a period of at least 12 weeks with a biologic disease modifying anti-rheumatic drug and were deemed refractory by the treating physician.
• Minimum of six swollen joint counts (SJC) and six tender joint counts (TJC) according to joint assessment.

For subjects with Sjögren's Disease (SjD)

• Prior diagnosis of Primary SjD as per 2016 ACR/EULAR criteria with confirmatory diagnosis in the 24 weeks preceding screening.
• Total Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) > 6.
• Salivary Flow Rate > 0.1 mL/min on stimulation.

For subjects with Idiopathic Inflammatory Myopathies (IIMs)

• Presence of a positive autoantibody (ANA >1:80 or RNP or SSA/SSB or other myositis specific autoantibodies.
• Refractory IIM as defined by inadequate response/intolerance to at least 3 months of glucocorticoids and/or at least one other immunosuppressive.
• Muscle biopsy or muscle MRI to confirm IIM diagnosis, where applicable, within 12 months prior to enrollment.

For Subjects with Systemic Sclerosis (SSc)

• Diagnosis of SSc in accordance with the ACR/EULAR 2013 classification.
• Modified Rodnan skin score (mRSS) > 10.
• Initial confirmatory diagnosis within 8 years of screening.
• Refractory SSc as defined by inadequate response/intolerance to at least 3 months of glucocorticoids and/or at least one other immunosuppressive.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 31 centers

• Artiva Investigational Site Tuscaloosa — Tuscaloosa
• Artiva Investigational Site Phoenix — Phoenix
• Artiva Investigational Site Tucson — Tucson
• Artiva Investigational Site Chula Vista — Chula Vista
• Artiva Investigational Site Covina — Covina
• Artiva Investigational Site Los Alamitos — Los Alamitos
• Artiva Investigational Site Los Angeles — Los Angeles
• Artiva Investigational Site Santa Ana — Santa Ana
• … and 23 more centers

Brazil · 6 centers

• Artiva Investigational Site Brasília — Brasília
• Artiva Investigational Site Cuiabá — Cuiabá
• Artiva Investigational Site Porto Alegre — Porto Alegre
• Artiva Investigational Site Rio Grande — Rio Grande
• Artiva Investigational Site Sao Paulo — São Paulo
• Artiva Investigational Site São Paulo — São Paulo

France · 3 centers

• Artiva Investigational Site Marseille — Marseille
• Artiva Investigational Site Montpellier — Montpellier
• Artiva Investigational Site Toulouse — Toulouse

Bulgaria · 2 centers

• Artiva Investigational Site Plovdiv — Plovdiv
• Artiva Investigational Site Sofia — Sofia

Germany · 2 centers

• Artiva Investigational Site Bonn — Bonn
• Artiva Investigational Site Munchen — München

Poland · 2 centers

• Artiva Investigational Site Bydgoszcz — Bydgoszcz
• Artiva Investigational Site Warszawa — Warsaw

Romania · 2 centers

• Artiva Investigational Site Bucuresti — Bucharest
• Artiva Investigational Site Bucharest — Bucharest

Italy · 1 center

• Artiva Investigational Site Brescia — Brescia

Portugal · 1 center

• Artiva Investigational Site Vila Nova De Gaia — Vila Nova de Gaia

Serbia · 1 center

• Artiva Investigational Site Belgrade — Belgrade

Spain · 1 center

• Artiva Investigational Site Sevila — Seville

Identifiers

NCT: NCT06991114 · AB-101-05

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗