Open-label Single-Center Study to Evaluate the Safety and Efficacy of Combining Rituximab and AB-101 in B-cell Associated Autoimmune Diseases.

NCT06581562 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRIS-RD-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and activity of AB-101 in combination with rituximab in B-cell associated autoimmune diseases where rituximab is currently FDA approved (e.g., Rheumatoid Arthritis (RA), Pemphigus Vulgaris (PV), Granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA) as a therapeutic, or is recommended (e.g., in Systemic Lupus Erythematosus (SLE) as a cornerstone for disease management.

Conditions

Rheumatoid Arthritis; Pemphigus Vulgaris; Granulomatosis With Polyangiitis; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events and relationship to study drug

  We will evaluate the Incidence of adverse events and relationship to study drug

  From the time of consent through 104 weeks after initiation of study treatment

• Incidence of Serious Adverse Events (SAE) and causality assessment

  We will evaluate the Incidence of adverse events and relationship to study drug

  From the time of consent through 104 weeks after initiation of study treatment

• Total hospitalizations, duration of hospitalizations through the course of the study

  We will evaluate the Incidence of adverse events and relationship to study drug

  From the time of consent through 104 weeks after initiation of study treatment

Secondary Outcomes (4)

• RA: Change From Baseline in DAS28 at Week 12 and 24

  Week 12 through 24

• PV: Change from baseline in the Pemphigus Disease Area Index (PDAI) at Week 12 and 24

  Week 12 through 24

• GPA / MPA: Change from baseline in the Birmingham Vasculitis Activity Score at Week 12 and 24

  Week 12 through 24

• SLE: Change from baseline in the SLE Disease Activity Index (SLEDAI) at Week 12 and 24

  Week 12 through 24

Other Outcomes (3)

• Pharmacokinetics and Immunogenicity

  at baseline and according to the scheduled of assessments

• Patient Reported Outcomes

  from the time of consent through 104 weeks after initiation of styudy treatment

• Pharmacodynamic Biomarkers

  from the time of consent through 104 weeks after initiation of styudy treatment

Study Arms (4)

Arm 1

EXPERIMENTAL

Arm 1 - Subjects with Rheumatoid Arthritis

Drug: AB-101; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

Arm 2

EXPERIMENTAL

Arm 2- Pemphigus Vulgaris

Drug: AB-101; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

Arm 3

EXPERIMENTAL

Arm 3 - Systemic Lupus Erythematosus

Drug: AB-101; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

Arm 4

EXPERIMENTAL

Arm 4- Subjects with Granulomatosis with polyangiitis / microscopic polyangiitis

Drug: AB-101; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

AB-101 DRUG

Subjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.

Also known as: ALLONK, RITUXIMAB, CYCLOPHOSPHAMIDE, FLUDARABINE

Arm 1; Arm 2; Arm 3; Arm 4

Rituximab DRUG

Subjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.

Arm 1; Arm 2; Arm 3; Arm 4

Cyclophosphamide DRUG

Subjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.

Arm 1; Arm 2; Arm 3; Arm 4

Fludarabine DRUG

Subjects in all 4 indications will receive only one cycle of treatment. Subjects with RA, PV or SLE will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2 and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 1000 mg on Day 1 and Day 15 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13 and Day 20 Subjects with GPA and MPA will receive one cycle of treatment as follows: 1. Fludarabine: 25 mg/m2 on Day 1, Day 2, and Day 3. 2. Cyclophosphamide: 1000 mg/m2 on Day 3 3. Rituximab: 375 mg/m2 on Day -2, Day 6, Day 13, and Day 20 4. AB-101: 1B NK cells (AlloNK) on Day 6, Day 13, and Day 20 The first dose of AB-101 should be administered at least 48 hours after the last infusion of the lymphodepletion regimen.

Arm 1; Arm 2; Arm 3; Arm 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or female subjects, ≥ 18 years of age at the time of signing informed consent.
• Ability to understand the requirements of the study.
• Willingness to provide written informed consent.
• Willingness to comply with the study protocol procedures.
• Women of childbearing potential and all male participants must agree to use two acceptable methods of contraception together to avoid pregnancy. The following are examples of acceptable methods of contraception including:
• Established use of oral, inserted, injected, or implanted hormonal methods of contraception.
• Correctly placed copper containing intrauterine device (IUD).
• Male condom or female condom used WITH a spermicide (i.e., foam, gel, film, cream, suppository).
• Male sterilization with appropriately confirmed absence of sperm in the post-vasectomy ejaculate.
• Bilateral tubal ligation or bilateral salpingectomy.
• Oral steroids will be tapered to \<20 mg/day of prednisone (or equivalent) at least 1 week prior to the first study treatment. The tapering schedule will be at the discretion of the Investigator.
• Subjects must have a predicted diffusing capacity for carbon monoxide (DLCO) of \>60% and a forced expiratory volume 1 (FEV1) \>70% at screening.
• Left ventricular ejection fraction (LVEF) ≥ 45% by Echocardiogram. Rituximab and AB-101 in autoimmune diseases Clinical Study Protocol V. 1.1 Confidential Page 11 of 101 April 16, 2024
• Baseline laboratory values fulfilling the following requirements to demonstrate adequate hematologic, renal, and hepatic function:
• RA PV MPA / GPA SLE Absolute neutrophil count (/mm3)

You may not qualify if:

• \. Known hypersensitivity or contraindication to any drug products or any component of the drug products they plan to receive (e.g., cyclophosphamide, fludarabine, rituximab, AB-101).
• \. History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies or DMSO (Dimethyl sulfoxide).
• \. Prior treatment with any B-cell targeted therapy within 3 months of the start of the planned lymphodepletion regimen (e.g., rituximab or other anti-CD20, anti-CD19, anti-CD22 monoclonal antibodies) 6. Prior treatment with any autologous or allogeneic cell therapy approach using genetically modified immune cells (e.g., T, NK, macrophages, or gamma-delta T cells modified with chimeric antigen receptors (CAR)).
• \. Received any of the following within 6 months of the start of the planned lymphodepletion regimen:
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• Immunoglobulin replacement therapies (IV or SC)
• Plasmapheresis. 8. History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant, or are due to receive such transplantation.
• \. Known past or current malignancy except for cervical carcinoma of stage 1B or less, noninvasive basal cell or squamous cell skin carcinoma, Noninvasive, superficial bladder cancer, Prostate cancer with a current prostate specific antigen (PSA) level \< 0.1 ng/m, Any curable cancer with a complete response duration of \> 2 years 10. Any history of a B cell malignancy, even if subjects have achieved a complete response.
• \. Known clinically significant cardiac disease: Within the prior 6 months of signing the informed consent form, onset of unstable angina pectoris or acute myocardial infarction; congestive heart failure (grade III or IV as classified by the New York Heart Association), pericarditis present during screening or at baseline, heart rate-corrected QT interval (QTcF) prolongation \> 470 msec at screening, unless secondary to stable conduction disorders (e.g., left bundle-branch block) 12. Unresolved toxicities from prior therapy, defined as having not resolved to Grade ≤ 1, or to the levels dictated in the eligibility criteria.
• \. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to RA, PV, GPA/MPA, SLE (e.g., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy, or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.
• \. Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
• \. Have any signs or symptoms of illness/infection or have received any vaccinations (live or inactivated) within 6 weeks of Day 1.
• \. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within ≤ 1 year prior to Day 1.
• \. Human immunodeficiency virus (HIV) infection, based on laboratory testing performed during the screening period.
• \. Currently pregnant or lactating (breast feeding must not be started within 6 months of the last dose of AB-101).

Sponsors & Collaborators

• IRIS Research and Development, LLC: lead
• Artiva Biotherapeutics, Inc.: collaborator

Study Sites (1)

IRIS Research and Development, LLC

Plantation, Florida, 33324, United States

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid; Pemphigus; Granulomatosis with Polyangiitis; Lupus Erythematosus, Systemic

Interventions

Rituximab; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases, Vesiculobullous; Skin Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Guillermo J. Valenzuela, M.D.

  IRIS Research and Development, LLC

  PRINCIPAL INVESTIGATOR

• Kathy I. Perez, M.D.

  IRIS Research and Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Kathy I Perez, M.D.

CONTACT

954-476-2338; kperez@irisrheumatology.com

Jhon Galindo, B.S.

CONTACT

9544762338; jgalindo@irisrheumatology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label Single-Center Study

Study Record Dates

• First Submitted: August 2, 2024
• First Posted: September 3, 2024
• Study Start: May 15, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 3, 2024

Record last verified: 2024-08

Locations

US (1)