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

Trial Summary

What is the purpose of this trial?

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.

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.

What evidence supports the effectiveness of the drug AB-101 + Rituximab for autoimmune diseases?

Rituximab, a component of the treatment, has been shown to be effective in treating various autoimmune diseases, including rheumatoid arthritis, by targeting B-cells (a type of immune cell) and reducing inflammation. It has been used successfully in patients who do not respond to standard treatments, although there is a risk of infections with its use. ^{1 2 3 4 5}

Is the combination of AB-101 and Rituximab safe for humans?

Rituximab, used in treating autoimmune diseases, has been generally well tolerated, but it can increase the risk of infections, including rare cases of a serious brain infection called progressive multifocal leucoencephalopathy (PML). Common side effects include infusion reactions, which can be reduced with steroids, and repeated use may lead to low levels of antibodies, increasing infection risk. ^{1 3 6 7 8}

What makes the drug AB-101 + Rituximab unique for treating autoimmune diseases?

The combination of AB-101, a novel treatment, with Rituximab, which targets B cells involved in autoimmune diseases, offers a potentially enhanced approach by combining different mechanisms to reduce immune system activity. Rituximab is already known for its effectiveness in depleting B cells, which are crucial in many autoimmune conditions, and the addition of AB-101 may provide additional benefits. ^{9 10 11 12 13}

Research Team

Guillermo Valenzuela

Principal Investigator

IRIS Research and Development, LLC

Kathy I. Perez, M.D.

Principal Investigator

IRIS Research and Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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 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]

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 (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]

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]

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, 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, 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Anti-CD20 therapy in rheumatoid arthritis]. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID). [2021]

3. United States pubmed.ncbi.nlm.nih.gov

B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Rituximab treatment of refractory rheumatoid arthritis. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. France pubmed.ncbi.nlm.nih.gov

[Ulcerative colitis: exceptional consequence after rituximab therapy]. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. Italy pubmed.ncbi.nlm.nih.gov

Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Anti B cell therapy (rituximab) in the treatment of autoimmune diseases. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Rituximab: beyond simple B cell depletion. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

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

12. Switzerland 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. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). [2019]