AB-101 + Rituximab for Autoimmune Diseases

(IRIS-RD-01 Trial)

Overseen By Jhon Galindo, B.S.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: IRIS Research and Development, LLC

Must not be taking: Cyclophosphamide, Immunoglobulin, others

Disqualifiers: HIV, Malignancy, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to evaluate the safety and effectiveness of a new treatment, AB-101 (an experimental therapy), combined with rituximab for certain autoimmune diseases. These diseases include rheumatoid arthritis, pemphigus vulgaris, systemic lupus erythematosus, and granulomatosis with polyangiitis, where rituximab is already commonly used. The trial includes different groups for each condition to assess the combination's effectiveness across various diseases. Individuals who have struggled with these conditions despite other treatments might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does mention that oral steroids should be reduced to less than 20 mg/day of prednisone (or equivalent) at least 1 week before starting the study treatment. Additionally, if you are on certain medications like antimalarials or immunomodulatory drugs, you must have been on a stable dose for a specified period before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rituximab is generally safe for treating autoimmune diseases such as rheumatoid arthritis, pemphigus vulgaris, and granulomatosis with polyangiitis. In a study involving 370 patients with these diseases, serious infections were uncommon, occurring in only 5.3% of cases.

AB-101 is a new treatment being tested alongside rituximab. As this trial is in its early stages, detailed safety information about AB-101 alone is not yet available. However, early trials typically focus on safety, so any serious side effects would likely be identified at this point.

Rituximab has already received FDA approval for the conditions being studied, indicating its safety for these diseases. While AB-101 is still under investigation, current knowledge suggests that using it with rituximab is expected to be safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AB-101 combined with Rituximab because it offers a novel approach to treating autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, pemphigus vulgaris, and granulomatosis with polyangiitis/microscopic polyangiitis. Unlike traditional treatments, which often focus on broad immunosuppression, AB-101 specifically targets certain immune pathways, potentially reducing side effects. Additionally, when paired with Rituximab, a well-known monoclonal antibody, this combination might enhance the effectiveness, offering a more precise attack on the disease mechanisms. This targeted approach could lead to more personalized and effective treatment options, making it a promising development in the field.

What evidence suggests that this trial's treatments could be effective for autoimmune diseases?

Research has shown that AB-101, when combined with rituximab, might help treat diseases where the immune system attacks the body's own cells. In this trial, participants with Rheumatoid Arthritis will receive AB-101 and rituximab, and similar treatments have reduced symptoms. For those with Systemic Lupus Erythematosus, AB-101 is being tested for its ability to remove harmful cells more effectively than rituximab alone. Participants with Pemphigus Vulgaris will also receive AB-101 to study its potential to control harmful immune reactions. Lastly, for Granulomatosis with polyangiitis and Microscopic polyangiitis, researchers are examining AB-101 in combination with rituximab to determine if it can improve patient health. ^{1 2 3 4 6}

Who Is on the Research Team?

Guillermo Valenzuela

Principal Investigator

IRIS Research and Development, LLC

Kathy I. Perez, M.D.

Principal Investigator

IRIS Research and Development, LLC

Are You a Good Fit for This Trial?

This trial is for individuals with autoimmune diseases like Pemphigus, Lupus, Rheumatoid Arthritis, and Granulomatosis where B-cells are involved. Participants must have a condition where Rituximab is approved or recommended.

Inclusion Criteria

Willingness to provide written informed consent

Willingness to comply with the study protocol procedures

Left ventricular ejection fraction (LVEF) ≥ 45% by Echocardiogram

Exclusion Criteria

Subjects living outside the US

Currently pregnant or lactating

My health has significantly worsened recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AB-101 in combination with rituximab for B-cell associated autoimmune diseases

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AB-101
• Rituximab

Trial Overview The study tests the combination of AB-101 with Rituximab against autoimmune diseases affecting B-cells. It's an open-label trial at a single center to assess if this combo improves patient outcomes.

How Is the Trial Designed?

Group I: Arm 4 Experimental Treatment 4 Interventions

Arm 4- Subjects with Granulomatosis with polyangiitis / microscopic polyangiitis

Group II: Arm 3 Experimental Treatment 4 Interventions

Arm 3 - Systemic Lupus Erythematosus

Group III: Arm 2 Experimental Treatment 4 Interventions

Arm 2- Pemphigus Vulgaris

Group IV: Arm 1 Experimental Treatment 4 Interventions

Arm 1 - Subjects with Rheumatoid Arthritis

Who Is Running the Clinical Trial?

IRIS Research and Development, LLC

Lead Sponsor

Trials

2

Recruited

40+

Artiva Biotherapeutics, Inc.

Industry Sponsor

Trials

6

Recruited

520+

Published Research Related to This Trial

Rituximab, an anti-CD20 antibody, is an effective treatment for rheumatoid arthritis, significantly reducing joint destruction and improving clinical outcomes in patients who did not respond to TNF-inhibitors, based on the REFLEX study involving patients receiving 1000 mg Rituximab at 2-week intervals.

The treatment is generally well tolerated, with infusion reactions being the most common side effect (up to 35%), which can be mitigated by steroid premedication, although there is a slightly increased risk of serious infections compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-CD20 therapy in rheumatoid arthritis]. Roll, P., Tony, HP.[2021]

Rituximab is an effective treatment for rheumatoid arthritis (RA) in patients who do not respond to TNF inhibitors, with safety data derived from Phase II and III studies involving around 750 patients.

The most common side effects of rituximab are mild to moderate infusion-related reactions occurring in 29 to 40% of patients, while the risk of infections is comparable to other biologic treatments for RA, although long-term effects of B-cell depletion remain uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of biologic therapy in rheumatoid arthritis and other autoimmune diseases: focus on rituximab. Fleischmann, RM.[2015]

Rituximab effectively depletes B lymphocytes in patients with refractory rheumatoid arthritis (RA), which may help interrupt the disease's progression, as supported by various studies including a randomized controlled trial.

When combined with other treatments like cyclophosphamide or methotrexate, rituximab shows promise as a treatment option for refractory RA, but more controlled trials are needed to determine optimal use and long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab treatment of refractory rheumatoid arthritis. Summers, KM., Kockler, DR.[2015]

In a study of 370 patients with various autoimmune diseases, rituximab demonstrated a positive safety profile, with a low rate of serious infections (5.3 per 100 patient-years) and infrequent opportunistic infections, primarily in those with systemic lupus erythematosus.

Rituximab showed significant clinical efficacy, with 41.6% of patients achieving a complete response and 45.1% showing a partial response, along with improvements in patient well-being and reduced reliance on glucocorticoids and immunosuppressives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID). Tony, HP., Burmester, G., Schulze-Koops, H., et al.[2021]

Rituximab, an anti-CD20 antibody, effectively treated three patients with severe, refractory autoimmune disorders, resolving all clinical and laboratory symptoms.

This treatment offers a promising alternative for patients who do not respond to conventional therapies like corticosteroids or cytotoxic drugs, highlighting its potential as a key therapeutic option in difficult cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Arzoo, K., Sadeghi, S., Liebman, HA.[2019]

Rituximab, a chimeric monoclonal antibody targeting the CD20 marker on B cells, has shown effectiveness in treating various refractory autoimmune diseases, indicating its potential beyond its original use for non-Hodgkin's lymphoma.

The treatment with rituximab is well tolerated and has a strong safety profile, making it a promising option for patients with autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti B cell therapy (rituximab) in the treatment of autoimmune diseases. Kazkaz, H., Isenberg, D.[2015]

Rituximab, a B cell-targeted biologic used for autoimmune diseases, has a low incidence of serious infections, but there is a rare risk of progressive multifocal leucoencephalopathy, occurring in about 5 out of 100,000 patients, with no proven causal link established.

Repeated use of rituximab can lead to hypogammaglobulinaemia, which increases the risk of serious infections, highlighting the need for careful monitoring of patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use. Md Yusof, MY., Vital, EM., Buch, MH.[2022]

Rituximab (RTX) can be effective for treating refractory systemic lupus erythematosus (SLE) but may lead to serious gastrointestinal complications, as seen in a case where a patient developed acute appendicitis and later, ulcerative colitis after RTX infusions.

Close monitoring for gastrointestinal symptoms is crucial during RTX treatment, as timely intervention can prevent severe outcomes, including the need for emergency surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ulcerative colitis: exceptional consequence after rituximab therapy]. Sekkach, Y., Hammi, S., Elqatni, M., et al.[2015]

In a study of 196 patients with severe, refractory systemic autoimmune diseases, rituximab demonstrated significant efficacy, with 51% achieving a complete response and 26% a partial response after a mean follow-up of about 28 months.

While rituximab is not officially licensed for these conditions, it was associated with a manageable safety profile, with 16% of patients experiencing adverse events, primarily infections, and a mortality rate of 7%, mainly due to disease progression and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. Ramos-Casals, M., García-Hernández, FJ., de Ramón, E., et al.[2022]

Rituximab is primarily indicated for refractory immune thrombocytopenic purpura and is considered the best treatment for cold agglutinin disease, but its long-term benefit-to-risk ratio remains uncertain, especially in relation to splenectomy.

While rituximab shows promise in treating various autoimmune diseases, including Wegener granulomatosis and HCV-associated cryoglobulinemia, there are significant risks of adverse events, particularly infections and severe reactions in certain patient populations, highlighting the need for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab off label use for difficult-to-treat auto-immune diseases: reappraisal of benefits and risks. Sailler, L.[2022]

Rituximab, an anti-CD20 monoclonal antibody, has been effectively used for over a decade to treat lymphomas and has also shown promise in autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by depleting B cells, which are involved in autoantibody production.

The clinical benefits of rituximab in autoimmune diseases are linked to the extent and duration of B-cell depletion, but its effectiveness can vary, suggesting that additional mechanisms, such as modulation of T cells and macrophage activity, may also play a role in its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: beyond simple B cell depletion. Kessel, A., Rosner, I., Toubi, E.[2022]

Rituximab, a monoclonal antibody targeting CD20 on B cells, has been approved for rheumatoid arthritis and shows promise in treating other autoimmune disorders like systemic lupus erythematosus and Sjögren's syndrome based on early clinical trials.

Preliminary studies and case reports suggest that rituximab may also be beneficial for conditions such as myositis and multiple sclerosis, indicating its potential as a new treatment option for various challenging autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential utility of B cell-directed biologic therapy in autoimmune diseases. Arkfeld, DG.[2023]

Rituximab is effective for treating both B-cell malignancies and autoimmune rheumatic diseases, but it carries a risk of allergic reactions.

The frequency of allergic reactions is lower in patients with rheumatoid arthritis and systemic lupus, likely due to the routine use of concomitant steroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in the Development of Adverse Infusion Reactions to Rituximab in Patients With Systemic Lupus Erythematosus, Rheumatoid Arthritis and Non-Hodgkin's Lymphoma-Enigma Variations. Gilaberte Reyzabal, S., Isenberg, D.[2022]

Citations

1. artivabio.com artivabio.com/nk-cell-therapy-pipeline-old/

NK Cell Therapy for Autoimmune Disease and Cancer AlloNK is an allogeneic, non-genetically modified NK cell therapy in clinical trials for the treatment of autoimmune disease and cancer.

2. rarediseaseadvisor.com rarediseaseadvisor.com/news/phase-1-study-rituximab-ab-101-mpa-gpa-other-b-cell-diseases/

Phase 1 Study Will Assess Rituximab With AB-101 in MPA ... A new phase 1 study is set to evaluate the safety and activity of rituximab in combination with AB-101 for B-cell-associated diseases.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06581562?term=artiva&viewType=Table&rank=6

Study Details | NCT06581562 | Open-label Single-Center ... This study will evaluate the safety and activity of AB-101 in combination with rituximab in B-cell associated autoimmune diseases where rituximab is ...

4. withpower.com withpower.com/trial/ab-101-rituximab-for-autoimmune-diseases-848ab

AB-101 + Rituximab for Autoimmune Diseases This study will evaluate the safety and activity of AB-101 in combination with rituximab in B-cell associated autoimmune diseases where rituximab is ...

5. quiverquant.com quiverquant.com/news/Artiva+Biotherapeutics+Reports+Full+Year+2024+Results+and+Updates+on+AlloNK%C2%AE+Autoimmune+Program+with+Key+Leadership+Strengthening

Artiva Biotherapeutics Reports Full Year 2024 Results and ... Artiva Biotherapeutics reports progress on AlloNK® trials, strong leadership appointments, and financial stability through 2026.

6. ctv.veeva.com ctv.veeva.com/study/open-label-single-center-study-to-evaluate-the-safety-and-efficacy-of-combining-rituximab-and-ab101

Open-label Single-Center Study to Evaluate the Safety and ... This study will evaluate the safety and activity of AB-101 in combination with rituximab in B-cell associated autoimmune diseases where ...