~30 spots leftby Oct 2026

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

Recruiting at1 trial location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Artiva Biotherapeutics, Inc.
Must be taking: B-cell depleting mAb
Disqualifiers: Malignancy, Cardiac disease, Viral infections, others
No Placebo Group
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

AB-101 (also known as AlloNK) is an off-the shelf, allogeneic cell product made of "natural killer" cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that is known to enhance the effect of monoclonal antibody therapies. 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 respond to previous standard of care treatment approaches, or other forms of refractory systemic lupus erythematosus. 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 cyclophosphamide and fludarabine in adult subjects with relapsed/refractory lupus nephritis Class III or IV, with or without the presence of Class V, or other forms of refractory systemic lupus erythematosus. Patients will be assigned to receive either AB-101 alone as monotherapy or in combination with a B-cell depleting mAb (e.g., rituximab, obinutuzumab). All patients will receive at least 1 treatment cycle of AB-101, followed by scheduled assessments of overall health and response status. Patients may receive up to 2 cycles of treatment spaced 24 weeks apart.

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.

What data supports the effectiveness of the drug AB-101 + B-cell Depleting mAb for Lupus Nephritis?

B-cell depletion has been used successfully in treating other autoimmune diseases like rheumatoid arthritis, and some small studies have shown positive results for lupus nephritis. However, large trials with rituximab, a B-cell depleting drug, did not meet their main goals for lupus nephritis, indicating mixed results.12345

How is the drug AB-101 + B-cell Depleting mAb different from other lupus nephritis treatments?

AB-101 (AlloNK) combined with a B-cell depleting monoclonal antibody (mAb) is unique because it targets both natural killer (NK) cells and B cells, which are central to the disease process in lupus nephritis. This dual approach may offer a novel mechanism compared to traditional treatments that primarily focus on B-cell depletion alone.12467

Research Team

SB

Sudhir Borgonha, MD

Principal Investigator

Artiva Biotherapeutics

Eligibility Criteria

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.
See 1 more

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.
See 1 more

Trial Timeline

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

Treatment Details

Interventions

  • AB-101 (Cell Therapy)
  • Rituximab (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Phase 1: Dose confirmation of AB-101 plus Rituximab combinationExperimental Treatment4 Interventions
Group II: Phase 1: Dose confirmation of AB-101 plus Obinutuzumab combinationExperimental Treatment4 Interventions
Group III: Phase 1: Dose confirmation of AB-101 as MonotherapyExperimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Artiva Biotherapeutics, Inc.

Lead Sponsor

Trials
6
Recruited
520+

Findings from Research

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.
B-cell depletion in the treatment of lupus nephritis.Gregersen, JW., Jayne, DR.[2021]
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.
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]
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.
Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis.Frieri, M., Heuser, W., Bliss, J.[2020]

References

B-cell depletion in the treatment of lupus nephritis. [2021]
Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis. [2022]
Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis. [2020]
B cells in systemic lupus erythematosus: Targets of new therapies and surveillance tools. [2022]
Immunoadsorption: a new strategy to induce remission in membranous lupus nephritis. [2021]
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. [2022]
Clinical improvements in proliferative vs membranous lupus nephritis following B-cell depletion: pooled data from two cohorts. [2015]