Daratumumab for Lupus Nephritis

Overseen By Corbyn Bendtsen

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Immunosuppressants, Cyclophosphamide, Rituximab

Disqualifiers: Pregnancy, Hepatitis, HIV, Anemia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

12 Participants Needed

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like immunosuppressive drugs (e.g., cyclosporine, tacrolimus, azathioprine) if you've used them in the last 3 months, and cyclophosphamide if used in the last 6 months. You can continue taking MMF (mycophenolate mofetil) but no more than 1500 mg per day. If you're on corticosteroids, you must not exceed 10 mg of prednisone or its equivalent 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}

How is the drug daratumumab unique in treating lupus nephritis?

Daratumumab is unique for lupus nephritis because it is an anti-CD38 monoclonal antibody that targets specific immune cells, offering a novel approach for patients who do not respond to standard treatments. It is administered intravenously and has shown promising results in reducing disease activity and improving kidney function in patients with treatment-resistant lupus nephritis. ^{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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Subjects receive Daratumumab once weekly for 8 weeks and then once every 2 weeks for 8 additional doses

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes

24 months

Treatment Details

Interventions

• Daratumumab

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).

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

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]

In the TULIP-LN trial involving 147 patients with active lupus nephritis, the intensified regimen of anifrolumab (900 mg followed by 300 mg) showed a higher rate of complete renal response at Week 104 compared to the basic regimen and placebo (27.3% vs 18.6% and 17.8%).

The safety profile of anifrolumab remained consistent over two years, with 72% of patients reporting at least one adverse event, but serious adverse events were relatively low, suggesting that anifrolumab is a tolerable treatment option for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. Jayne, D., Rovin, B., Mysler, E., et al.[2023]

Belimumab is on track to become the first new drug approved for systemic lupus erythematosus (SLE) in decades, showing promising efficacy in recent trials.

Preliminary results for epratuzumab also indicate potential benefits for lupus patients, suggesting that biologics may significantly improve treatment options and outcomes for this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologicals for the treatment of systemic lupus erythematosus? Gunnarsson, I., van Vollenhoven, RF.[2013]

Traditional outcome measures for lupus nephritis, like doubling of serum creatinine and end-stage renal disease, are limited due to their low occurrence and the long time needed to observe them, making them less effective for evaluating treatment efficacy.

The review suggests using composite outcome measures, including remission and relapse rates, along with health-related quality of life assessments, to provide a more comprehensive evaluation of treatment effects in both small pilot studies and larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome criteria for lupus nephritis trials: a critical overview. Boumpas, DT., Balow, JE.[2019]

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]

Infliximab has demonstrated prolonged improvement in renal function for patients with renal lupus, based on small open studies, indicating its potential efficacy in this specific condition.

Belimumab, at a higher dosage of 10 mg/kg, has shown significant efficacy in treating systemic lupus erythematosus in two large randomized controlled studies, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The management of systemic lupus erythematosus with biological therapies]. Malaise, O., von Frenckell, C., André, B., et al.[2017]

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]

Two new FDA-approved treatments for lupus nephritis, belimumab and voclosporin, have shown promise in improving outcomes for patients, particularly in the context of childhood-onset systemic lupus erythematosus (SLE).

Despite the challenges in conducting clinical trials for lupus nephritis, these targeted therapies represent a significant advancement, and there is a growing need for research focused on their use in pediatric patients who are at higher risk for severe kidney damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in immunotherapies for lupus nephritis. Kaneko, M., Jackson, SW.[2023]

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]

In a case series of six patients with treatment-refractory lupus nephritis, daratumumab treatment led to significant improvements in disease activity and kidney function over 12 months, with mean disease activity scores dropping from 10.8 to 3.6.

Five out of six patients showed marked reductions in proteinuria and serum creatinine levels, alongside favorable changes in immune markers, suggesting that daratumumab could be a promising therapy for refractory lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab monotherapy for refractory lupus nephritis. Roccatello, D., Fenoglio, R., Caniggia, I., et al.[2023]

Nephrotic syndrome affects 2-7 per 100,000 children annually, with steroids achieving remission in 75-90% of cases, but some patients develop steroid-resistant forms that pose a higher risk for end-stage kidney disease.

Current treatments, including monoclonal antibodies like rituximab, have shown limited effectiveness, leading to a new proposed treatment combining rituximab with daratumumab to target a broader range of B-cell subtypes, including long-lived plasma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment. Angeletti, A., Bruschi, M., Kajana, X., et al.[2023]

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]