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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of daratumumab, a medication intended to aid individuals with lupus nephritis, a kidney condition caused by lupus. The goal is to determine if daratumumab can lead to complete or partial remission, meaning a reduction or disappearance of symptoms. Participants will receive the treatment over a specified period and will be monitored for any changes. The trial seeks individuals with active lupus nephritis confirmed by kidney biopsy and significant protein loss in their urine. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that daratumumab is likely to be safe for humans?

Previous studies have tested daratumumab for other conditions, providing some understanding of its safety. Although specific data for lupus nephritis is not yet available, daratumumab treats other diseases and has FDA approval for multiple myeloma, a type of cancer, suggesting general safety for that condition.

Some patients using daratumumab have reported side effects like tiredness and nausea. Serious side effects, such as low blood cell counts, are less common but can occur. It's important to remember that reactions to the drug can vary among individuals.

This trial focuses on safety, indicating some confidence in daratumumab's safety. However, the trial will offer more specific information on its safety for lupus nephritis. Participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus nephritis?

Unlike the standard treatments for lupus nephritis, which often include corticosteroids and immunosuppressants, daratumumab offers a novel approach by targeting CD38, a protein on immune cells. This mechanism is unique because it directly reduces the number of antibody-producing cells that contribute to inflammation in lupus nephritis. Researchers are excited because daratumumab could offer a more targeted treatment option with potentially fewer side effects than traditional therapies, which often affect the entire immune system. Additionally, daratumumab’s targeted action might lead to better long-term outcomes by specifically addressing the underlying immune dysfunction in lupus nephritis.

What evidence suggests that daratumumab might be an effective treatment for lupus nephritis?

Research has shown that daratumumab, the treatment under study in this trial, may help treat lupus nephritis. In a small study with six patients whose lupus nephritis did not improve with other treatments, most experienced significant improvement after taking daratumumab. Specifically, five out of the six patients showed reduced disease activity, indicating the drug's potential effectiveness. However, one patient did not experience any improvement, indicating that results can vary. These early findings suggest that daratumumab could be a useful option for those with difficult-to-treat lupus nephritis. ^{2 3 5 6 7}

Who Is on the Research Team?

Fernando Fervenza, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

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.

My kidney biopsy confirmed I have a specific type of lupus nephritis.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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 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 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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-3-lupus-nephritis-3-2021-16f25

Daratumumab for Lupus Nephritis · Info for Participants In a case series of six patients with treatment-refractory lupus nephritis, daratumumab treatment led to significant improvements in disease activity and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10427415/

Daratumumab monotherapy for refractory lupus nephritis One patient did not show any improvement after 6 months of therapy, and daratumumab was discontinued. In five patients, the mean disease ...

3. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... The median overall survival (OS) of MM patients has increased significantly with patients younger than 50 years of age experiencing a 10-year survival rate of ...

4. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/daratumumab-johnson-johnson-lupus-nephritis-likelihood-of-approval-2/

Daratumumab by Johnson & Johnson for Lupus Nephritis According to GlobalData, Phase II drugs for Lupus Nephritis have a 50% phase transition success rate (PTSR) indication benchmark for progressing ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04810754

NCT04810754 | An Open Label Study to Evaluate ... This is a monocenter, open-label Phase II trial recruting SLE patients with clinical and serologic activity despite state-of-the-art immunosuppressive therapy.

6. darzalex.com darzalex.com/clinical-results/

Clinical Results 91% (about 9 of 10) of patients responded to treatment with DARZALEX FASPRO ® in combination with lenalidomide and dexamethasone (DRd).

7. darzalexhcp.com darzalexhcp.com/

HCP Website | DARZALEX® (daratumumab) & DARZALEX ... You can see from the results presented that more patients achieved a complete response or better with DRd by 18 months vs Rd alone. Forty-nine point eight ...