AB-101 + B-cell Depleting mAb for Lupus Nephritis

Recruiting at 18 trial locations

Overseen By AB-101-03 Chanel Mansfield, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Artiva Biotherapeutics, Inc.

Must be taking: B-cell depleting mAb

Disqualifiers: Malignancy, Cardiac disease, Viral infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24-48 weeks

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AB-101, which uses special immune cells known as "natural killer" cells, to assist people with lupus nephritis, a kidney issue caused by lupus. The goal is to determine if AB-101 alone or combined with other medications can be safe and effective for those whose lupus nephritis hasn't improved with standard treatments. Suitable candidates have lupus nephritis Class III or IV, have tried at least two other treatments without success, and have ongoing issues confirmed by a kidney test. Participants will receive AB-101 treatment, either alone or with another drug (a B-cell depleting monoclonal antibody, such as Rituximab), and their health will be monitored to assess their response.

As a Phase 1 trial, this 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 information does not specify if you need to stop taking your current medications. However, since the trial involves specific treatments like AB-101 and B-cell depleting antibodies, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for detailed guidance.

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

Research has shown that AB-101, also known as AlloNK, is generally safe and well-tolerated. In studies, patients received doses of 1 billion and 4 billion cells without serious problems, suggesting AB-101's safety for humans.

When combined with rituximab, a protein that aids the immune system, safety remains a major focus. The FDA has given this combination a Fast Track designation, often indicating promising early evidence of safety and effectiveness.

Similarly, using AB-101 with obinutuzumab, another immune system protein, has shown good results in targeting certain cells. This combination also received Fast Track designation, indicating a positive safety profile.

Overall, these treatments appear well-tolerated based on current research, but ongoing studies will provide more information about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AB-101 for lupus nephritis because it offers a fresh approach compared to standard treatments like corticosteroids and immunosuppressants. Unlike these options, AB-101 works by targeting B-cells, which are pivotal in the autoimmune response seen in lupus nephritis. This treatment is being explored both alone and in combination with monoclonal antibodies like Rituximab and Obinutuzumab, which also target B-cells, potentially enhancing effectiveness. By directly addressing the underlying immune processes, AB-101 could offer more precise control over lupus nephritis symptoms with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for lupus nephritis?

Research has shown that AB-101, a type of natural killer (NK) cell product, might enhance the effectiveness of certain antibody treatments for lupus nephritis, a kidney condition. These NK cells can improve treatment outcomes by targeting and reducing B cells, which often contribute to autoimmune diseases like lupus nephritis. In this trial, participants will receive AB-101 in different treatment arms. One arm will combine AB-101 with rituximab, a treatment for B-cell non-Hodgkin lymphoma, which in previous studies resulted in a 64% complete response rate, suggesting potential benefits for lupus nephritis. Another arm will combine AB-101 with obinutuzumab, which has shown better kidney responses in lupus patients compared to a placebo, indicating promise when used with AB-101. These findings suggest that using AB-101, especially with these antibodies, could improve outcomes for people with relapsed or difficult-to-treat lupus nephritis. ^{1 4 6 7 8}

Who Is on the Research Team?

Michael Saddekni, M.D., PgDip, BCMAS

Principal Investigator

Artiva Biotherapeutics

Are You a Good Fit for This Trial?

This trial is for adults with Class III or IV lupus nephritis, a serious kidney condition caused by lupus, who haven't improved with standard treatments. Participants may also have Class V lupus nephritis. They must be able to receive the study medications and follow-up assessments.

Inclusion Criteria

Eligible subjects must have detectable anti-double stranded DNA antibody titers for enrollment

I have lupus affecting my kidneys (Class III or IV) and standard treatments haven't worked.

My kidney biopsy shows active lupus nephritis.

Exclusion Criteria

I have or had cancer types other than the one I'm seeking treatment for.

I have a known heart condition.

I have a significant lung condition or currently use tobacco.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive at least 1 cycle of AB-101, with the option for a second cycle spaced 24 weeks apart, in combination with a B-cell depleting mAb or as monotherapy

24-48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AB-101
• Rituximab

Trial Overview The trial tests AB-101 (AlloNK), an immune cell therapy designed to boost antibody treatments, in combination with rituximab after pre-treatment with cyclophosphamide and fludarabine. It aims to see if this combo is safe and effective for those whose lupus nephritis didn't respond to other therapies.

How Is the Trial Designed?

Group I: Phase 1: Dose confirmation of AB-101 plus Rituximab combination Experimental Treatment 4 Interventions

Group II: Phase 1: Dose confirmation of AB-101 plus Obinutuzumab combination Experimental Treatment 4 Interventions

Group III: Phase 1: Dose confirmation of AB-101 as Monotherapy Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Artiva Biotherapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

520+

Published Research Related to This Trial

In a study of 10 lupus nephritis patients treated with rituximab, 80% achieved partial remission within 2 months, with 50% later reaching complete remission, indicating the treatment's efficacy in managing this condition.

B cell depletion was well tolerated and associated with significant decreases in T cell activation markers, suggesting that B cells may play a role beyond just producing autoantibodies in the disease process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Sfikakis, PP., Boletis, JN., Lionaki, S., et al.[2022]

In a study of 18 patients with refractory lupus nephritis, rituximab therapy led to complete remission in 11 patients and partial remission in 2, indicating its efficacy in treating this condition.

However, patients with severe forms of lupus nephritis, particularly Class IV-G, showed poor responses to rituximab and were at risk of progressing to end-stage renal failure, highlighting the need for careful patient selection in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis. Davies, RJ., Sangle, SR., Jordan, NP., et al.[2022]

In a study of 43 lupus nephritis patients treated with rituximab, both membranous and proliferative types showed significant improvements in proteinuria and serum albumin levels within the first 6 months, indicating effective treatment outcomes.

The reduction in anti-dsDNA titres and improvements in complement C3 levels were similar for both types of lupus nephritis, suggesting that B-cell depleting therapy may be beneficial for both conditions, warranting further controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical improvements in proliferative vs membranous lupus nephritis following B-cell depletion: pooled data from two cohorts. Jónsdóttir, T., Gunnarsson, I., Mourão, AF., et al.[2015]

An 11-year-old girl with membranous lupus nephritis showed significant improvement in proteinuria after ten sessions of daily immunoadsorption, reducing protein levels from 8 g/l to 0.12 g/l.

Following immunoadsorption, treatment with rituximab led to complete B-cell depletion, and despite the return of B-cells and positive anti-dsDNA antibodies, the patient maintained complete remission for 18 months with normal renal function and negative proteinuria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoadsorption: a new strategy to induce remission in membranous lupus nephritis. Ulinski, T., Davourie-Salandre, A., Brocheriou, I., et al.[2021]

Belimumab was the first biological agent approved for treating systemic lupus erythematosus (SLE) in adults and has since been expanded to include pediatric patients and lupus nephritis, highlighting its efficacy in managing this complex autoimmune disease.

B cell targeting therapies, including rituximab and emerging agents like obinutuzumab, are crucial for treating refractory cases of SLE, and monitoring B cell levels can help predict treatment responses and guide personalized therapy strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B cells in systemic lupus erythematosus: Targets of new therapies and surveillance tools. Parodis, I., Gatto, M., Sjöwall, C.[2022]

Belimumab (Benlysta) is a monoclonal antibody that targets B cell signaling, offering a new treatment option for lupus nephritis, a serious complication of systemic lupus erythematosus (SLE).

Phase 3 clinical trials have shown that belimumab is clinically effective, suggesting it could become a new standard of care for managing lupus nephritis and its associated complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis. Frieri, M., Heuser, W., Bliss, J.[2020]

B-cell depletion is a promising therapeutic target for lupus nephritis, as B cells play a central role in the disease's pathogenesis, but large trials with rituximab and ocrelizumab did not show significant efficacy in treating this condition.

Despite the failure of major trials, smaller studies and case reports involving over 800 patients suggest that B-cell-depleting agents may still offer benefits for some patients with lupus nephritis, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-cell depletion in the treatment of lupus nephritis. Gregersen, JW., Jayne, DR.[2021]

Citations

1. trials.arthritis.org trials.arthritis.org/trials/NCT06265220

AB-101 in Combination With B-Cell Depleting mAb in Patients ... 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 ...

2. lupus.org lupus.org/news/drug-update-first-person-dosed-with-investigational-therapy-allonk-for-lupus-nephritis

First Person Dosed with Investigational Therapy AlloNK for ... A first person has been dosed with the investigational therapy, AlloNK® (also known as AB-101) for treatment of lupus nephritis, (LN, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06265220

NCT06265220 | AB-101 in Combination With B-Cell ... The primary objective is to assess the safety, tolerability and preliminary activity of AB-101 plus a B-cell depleting mAb (e.g., rituximab, obinutuzumab) after ...

4. jrheum.org jrheum.org/content/52/Suppl_1/235.1

POTENT AND SPECIFIC KILLING OF SLE B CELLS WITH ... AlloNK has the potential to be effective in combination with mAbs to induce deeper B cell depletion and improved efficacy, over the mAbs alone, in SLE and LN.

5. artivabio.com artivabio.com/nk-cell-therapy-pipeline/

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

6. investors.artivabio.com investors.artivabio.com/News-and-Events/news/news-details/2025/Artiva-Biotherapeutics-Announces-Refractory-Rheumatoid-Arthritis-as-Lead-Indication-Upcoming-Data-Releases-and-Corporate-Update/default.aspx

News Details "We look forward to sharing the emerging translational and safety data in mid-November, supporting AlloNK's profile as an outpatient-ready ...

7. s203.q4cdn.com s203.q4cdn.com/960442723/files/doc_news/Artiva-Biotherapeutics-Receives-FDA-Fast-Track-Designation-for-AlloNK-in-Lupus-Nephritis-2024.pdf

Artiva Biotherapeutics Receives FDA Fast Track Designation ... The FDA has granted Artiva. Fast Track designations for the treatment of lupus nephritis with AlloNK in combination with rituximab or.

8. cgtlive.com cgtlive.com/view/artiva-biotherapeutics-nk-cell-therapy-allonk-cleared-trial-systemic-lupus-erythematosus

Artiva Biotherapeutics' NK Cell Therapy AlloNK Cleared for ... According to a summary of the safety data in a press release from May 2023, AlloNK was well-tolerated at doses of 1 billion and 4 billion cells ...