An Open Label Study to Evaluate Daratumumab in Participants With Moderate to Severe Systemic Lupus Erythematosus

NCT04810754 | Unknown Phase 2

• 2 other identifiers: CCM-RNT-2021012021-000962-14
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a monocenter, open-label Phase II trial for refractory SLE patients currently on stable background immunosuppressive therapy. Treatment in this trial will be daratumumab weekly for a period of 8 weeks. This study will enroll 10 patients.

Conditions

Systemic Lupus Erythematosus

Keywords

SLE; Daratumumab; anti-CD38; plasma cells; anti-dsDNA antibodies; lupus; CD38

Outcome Measures

Primary Outcomes (1)

• Change in serum anti-dsDNA antibody titers

  The primary endpoint is the significant reduction of serum anti-dsDNA antibody titers after 8 repeated weekly injections of daratumumab at Week 12, i.e. 4 weeks after the last daratumumab injection, compared to baseline

  Week 12 (i.e. 4 weeks after last daratumumab injection)

Secondary Outcomes (6)

• Assess the Incidence of Treatment-Emergent Adverse Events

  through study completion, from screening up to Week 36

• Clinical outcome parameter

  Week 12

• SLE serology

  through study completion, up to Week 36

• GC sparing

  between Week 12 and Week 36

• Health-related quality of life

  through study completion, up to Week 36

Other Outcomes (3)

• Number and phenotype of peripheral blood leukocytes

  through study completion, up to Week 36

• Change in surface expression levels of CD38

  through study completion, up to Week 36

• Study drug concentration

  at Week 9

Study Arms (1)

Daratumumab subcutaneous

EXPERIMENTAL

open label daratumumab s.c., unblinded

Drug: Daratumumab Injection

Interventions

Daratumumab Injection DRUG

1800 mg per injection; 8 consecutive injections once a week; subcutaneous application in abdomen

Also known as: DARZALEX (trade name)

Daratumumab subcutaneous

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• diagnosis of SLE according to the 2019 EULAR/ACR Systemic Lupus Erythematosus classification criteria.
• age between 18 and 60 years, inclusive, at consent.
• have a body mass index (BMI) between 18 and 32 kg/m² (BMI = weight/height2), inclusive, and a body weight of no less than 35 kg.
• demonstrate moderate to severe disease based on SLEDAI-2K score ≥ 6 observed at screening
• SLEDAI-2K ≥ 4 for clinical features (i.e. SLEDAI excluding laboratory results) at screening
• have a positive anti-double stranded deoxyribonucleic acid (anti-dsDNA) test, as measured by enzyme-linked immunosorbent assay (ELISA) test.
• Failure or lack of tolerability of at least 2 previous state-of-the-art immunosuppressive drugs/immunomodulatory drugs including antimalarials (does not account for glucocorticoids).
• if using oral corticosteroids, must be receiving this medication for at least 4 weeks and on a stable dose equivalent to an average dose of \<20 mg of prednisone daily for at least 4 weeks prior to the first dose of study agent.
• if using immunosuppressive drugs within the past 6 months, must not have exceeded the following dose levels: methotrexate 25 mg/week, azathioprine 2mg/kg/day, mycophenolate mofetil (MMF) 3g/day, or mycophenolic acid (MPA) 1440mg/day.
• if using immunosuppressive drugs, must be using not more than 1 immunosuppressive drug (does not account for antimalarials and glucocorticoids) and not have used any additional immunosuppressive drug within the past 3 months prior to the first dose of study agent.

You may not qualify if:

• has any unstable or progressive manifestation of SLE (lupus cerebritis, optic neuritis, transverse myelitis, psychosis, uncontrolled seizures, systemic vasculitis, end-stage renal disease, rapidly progressive Class III or IV glomerulonephritis, isolated Class V lupus nephritis \[i.e. without coexistent Class I, II, III, or IV nephritis\], Class VI lupus nephritis, pulmonary hemorrhage, myocarditis) that is likely to warrant escalation in therapy beyond permitted background medications. Subjects requiring renal hemodialysis or peritoneal dialysis are also excluded.
• has or has had a history of any clinically significant medical illness, or medical disorders the investigator considers significant should exclude the participant, including (but not limited to), hematological disease, immune deficiency states, respiratory disease, cardiovascular disease (including poor peripheral venous access), hepatic or gastrointestinal (GI) disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
• has or has had a serious infection (e.g. sepsis, pneumonia, or pyelonephritis), or been hospitalized or received IV antibiotics for a serious infection during the 3 months prior to consent.
• had major surgery, (e.g. requiring general anesthesia) within 3 months before screening.
• has or has had an acute illness, including a common cold, within 2 weeks prior to first study treatment or has had a major illness or hospitalization within 3 months prior to consent.
• has other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis.
• has received, is known to have received, or is suspected to have an intolerance or hypersensitivity (including delayed-type hypersensitivity) to any monoclonal antibodies or antibody fragments, is known to have allergies or clinically significant reactions to human proteins, monoclonal XML File Identifier: O1ANMGHPajQP16EY/porgcGYJv8= Page 11/23 antibodies, or antibody fragments, or to any components of the formulation used in this study, including daratumumab.
• has received any live virus or bacterial vaccinations within 12 weeks prior to first study treatment or is expected to receive any live virus or bacterial vaccinations during the study or up to 20 weeks after last study treatment.
• has received B cell depleting therapy within 12 months prior to first administration of the study agent (e.g. rituximab, ocrelizumab or obinutuzumab),
• has received a therapy that inhibits B-cell activating factor (BAFF) (i.e. belimumab) within 3 months prior to first administration of the study agent.
• has received prior experimental immunosuppressive biologic therapy for lupus (other than that described as allowed), less than 5 half-lives or 6 months, whichever is longer prior to first administration of the study agent.
• has used oral or IV cyclophosphamide within 2 months prior to first administration of the study agent.
• has ever been exposed to daratumumab or any anti-CD38 antibodies (e.g. TAK-079, MOR202, isatuximab).
• has a history of, or ongoing, chronic or recurrent infection/diagnosed latent infection, including but not limited to, chronic renal infection, chronic chest infection (e.g. bronchiectasis), sinusitis, recurrent urinary tract infection (e.g. recurrent pyelonephritis), an open, draining, or infected skin wound, or an ulcer.
• has or has had a serious infection (e.g. sepsis, pneumonia or pyelonephritis) or has been hospitalized or received IV antibiotics for a serious infection during the 3 months prior to consent.

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Janssen-Cilag G.m.b.H: collaborator
• Labor Berlin-Charité Vivantes G.m.b.H: collaborator
• German Cancer Research Center: collaborator
• Charité Clinical Trial Office (CTO): collaborator

Related Publications (2)

• Ostendorf L, Burns M, Durek P, Heinz GA, Heinrich F, Garantziotis P, Enghard P, Richter U, Biesen R, Schneider U, Knebel F, Burmester G, Radbruch A, Mei HE, Mashreghi MF, Hiepe F, Alexander T. Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2020 Sep 17;383(12):1149-1155. doi: 10.1056/NEJMoa2023325.

  PMID: 32937047 BACKGROUND

• Ahmad SB, Jefferson JA. Targeting B Cells and Plasma Cells in Glomerular Disease. J Am Soc Nephrol. 2025 Jun 4;36(9):1844-1857. doi: 10.1681/ASN.0000000772.

  PMID: 40465397 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Tobias Alexander, MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobias Alexander, MD

CONTACT

+4930450; tobias.alexander@charite.de

Jan Zernicke, Dr.rer.medic

CONTACT

+4930450; jan.zernicke@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tobias Alexander, Principal investigator

Model Details: open label, unblinded

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 23, 2021
• Study Start: June 30, 2021
• Primary Completion: March 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 23, 2021

Record last verified: 2021-03