Daratumumab for Lupus Nephritis

Recruiting in Palo Alto (17 mi)

Overseen by Fernando Fervenza, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Mayo Clinic

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing daratumumab, a medication that helps the immune system, in patients with active lupus nephritis. The goal is to see if it can help these patients by reducing kidney damage caused by their disease.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot participate if you've taken certain immunosuppressive therapies like cyclosporine, tacrolimus, or azathioprine in the last 3 months, or cyclophosphamide in the last 6 months. You can be on MMF, but no more than 1500mg/day. If you're on corticosteroids, you can't exceed 10 mg of prednisone for more than 2 weeks.

What data supports the idea that Daratumumab for Lupus Nephritis is an effective drug?

The available research does not provide specific data on the effectiveness of Daratumumab for Lupus Nephritis. Instead, it discusses other treatments like belimumab, which has shown promising results in clinical trials for lupus nephritis. Belimumab is highlighted as a potential breakthrough in treatment, suggesting it might be more effective than current options. However, there is no direct comparison or data available for Daratumumab in the context of lupus nephritis. ^{1 2 3 4 5}

What safety data is available for Daratumumab in treating lupus nephritis?

The provided research does not contain safety data for Daratumumab or its other names (Darzalex, Darzalex SC, Darzalex Faspro) in the treatment of lupus nephritis. The studies focus on the safety and efficacy of belimumab and other therapies for systemic lupus erythematosus and lupus nephritis. ^{6 7 8 9 10}

Is the drug Daratumumab a promising treatment for lupus nephritis?

Yes, Daratumumab shows promise as a treatment for lupus nephritis. In a study, five out of six patients with difficult-to-treat lupus nephritis showed significant improvement in their condition after receiving Daratumumab. This suggests that the drug could be a potential option for treating this serious kidney condition. ^{1 11 12 13 14}

Research Team

Fernando Fervenza, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults with active lupus nephritis, confirmed by biopsy and proteinuria, can join this trial. They must have a certain level of kidney function (eGFR ≥ 30 ml/min/SA) and meet specific criteria for systemic lupus erythematosus. Excluded are those on high-dose steroids, pregnant or breastfeeding women, individuals with hepatitis B/C or HIV, severe anemia or low platelets, recent immunosuppressive therapy users, and anyone unable to consent.

Inclusion Criteria

I am 18 years old or older.

You have more than 500 milligrams of protein in your urine over a 24-hour period.

I have been diagnosed with lupus according to ACR criteria.

Exclusion Criteria

You have hepatitis B or C, or HIV.

You have severe anemia with low hemoglobin levels.

I am unable to give my consent.

Treatment Details

Interventions

• Daratumumab (Monoclonal Antibodies)

Trial Overview The trial is testing Daratumumab's ability to induce remission in patients with active lupus nephritis. Participants will receive the drug to see if it safely and effectively reduces their disease activity compared to standard treatments.

Participant Groups

Group I: Daratumumab Experimental Treatment 1 Intervention

Subjects diagnosed with lupus nephritis will receive Daratumumab once weekly for 8 weeks and then once every 2 weeks for 8 additional does (+/- 4 days). Subjects will be followed for a total of 24 months (18 months after the last daratumumab administration).

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

Findings from Research

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]

In a study of 149 patients with systemic lupus erythematosus, Lupuzor showed significant efficacy, with 53.1% of patients achieving a positive response at week 12 compared to 36.2% in the placebo group.

Lupuzor was generally well tolerated, with the most common side effect being mild injection-site erythema, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial. Zimmer, R., Scherbarth, HR., Rillo, OL., et al.[2021]

A pooled analysis of safety data from 4170 patients across multiple clinical trials showed that belimumab has a similar safety profile to placebo, with comparable rates of adverse events and serious adverse events in both groups.

Belimumab demonstrated a positive benefit-risk profile for treating systemic lupus erythematosus (SLE), with a slightly higher incidence of post-infusion reactions but no significant increase in severe adverse events or mortality compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of belimumab in adult patients with systemic lupus erythematosus: Results of a large integrated analysis of controlled clinical trial data. Wallace, DJ., Atsumi, T., Daniels, M., et al.[2022]

In a study of 38 Portuguese patients with Systemic Lupus Erythematosus (SLE), belimumab demonstrated significant effectiveness, with SLE Responder Index (SRI) response rates increasing from 51.9% at 6 months to 91.7% at 24 months, indicating a reduction in disease activity.

Belimumab was associated with a good safety profile, with only five patients experiencing adverse events, primarily infections, and the treatment led to a significant decrease in disease activity markers and daily steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab in the treatment of Portuguese Systemic Lupus Erythematosus patients: a real-life multicenter study. Fernandes, BM., Barreira, S., Fonseca, JE., et al.[2021]

In a study involving 364 patients with systemic lupus erythematosus (SLE), long-term treatment with belimumab combined with standard therapy demonstrated a stable or declining incidence of adverse events over 4 years, indicating a favorable safety profile.

The most common side effects were mild, such as arthralgia and upper respiratory infections, and serious infusion reactions were rare, suggesting that belimumab can be safely administered for extended periods in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Merrill, JT., Ginzler, EM., Wallace, DJ., et al.[2013]

A patient with Crohn's disease developed lupus nephritis after long-term treatment with adalimumab, highlighting that this TNF-alpha inhibitor can trigger lupus-related conditions, including kidney inflammation.

Discontinuing adalimumab led to significant improvement in the patient's kidney function and a reduction in lupus-related antibodies, suggesting that stopping the medication can reverse its adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab-Induced Lupus Nephritis: Case Report and Review of the Literature. Kazzi, B., Gudenkauf, B., Fine, D., et al.[2023]

Rituximab (RTX) showed a significant improvement in complete renal response (CRR) and partial renal response (PRR) when combined with cyclophosphamide (CYC) compared to CYC alone, with CRR rates of 64% versus 21%.

The effectiveness of RTX varied among different ethnic groups, with CRR rates of 77% for Caucasian, 38% for East Asian, and 28% for Hispanic patients, indicating that patient demographics may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab use as induction therapy for lupus nephritis: a systematic review. Stolyar, L., Lahita, RG., Panush, RS.[2021]

References

1. India pubmed.ncbi.nlm.nih.gov

Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis. [2020]

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

Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Biologicals for the treatment of systemic lupus erythematosus? [2013]

5. England pubmed.ncbi.nlm.nih.gov

Outcome criteria for lupus nephritis trials: a critical overview. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Safety of belimumab in adult patients with systemic lupus erythematosus: Results of a large integrated analysis of controlled clinical trial data. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[The management of systemic lupus erythematosus with biological therapies]. [2017]

8. Portugal pubmed.ncbi.nlm.nih.gov

Belimumab in the treatment of Portuguese Systemic Lupus Erythematosus patients: a real-life multicenter study. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Recent advances in immunotherapies for lupus nephritis. [2023]

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

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. [2013]

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

Daratumumab monotherapy for refractory lupus nephritis. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment. [2023]

13. Turkey pubmed.ncbi.nlm.nih.gov

Adalimumab-Induced Lupus Nephritis: Case Report and Review of the Literature. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Rituximab use as induction therapy for lupus nephritis: a systematic review. [2021]