The Primary Objective of the Trial is to Evaluate the Effect of the Addition of Belantamab Mafodotin to Standard of Care Therapy on the Titres of Serum Anti-dsDNA Antibodies in Patients With Previously Treated SLE.

NCT07844200 | Not Yet Recruiting Phase 2

• 2 other identifiers: MSCB-BEA-0012026-526729-16-00
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of the trial is to evaluate the effect of the addition of belantamab mafodotin to standard of care therapy on the titres of serum anti-dsDNA antibodies in patients with previously treated SLE. Estimand for Primary Endpoint: Change of serum anti-dsDNA antibody titers at 24 weeks of treatment vs baseline.

Conditions

SLE - Systemic Lupus Erythematosus

Keywords

belantamab mafodotin; previously treated SLE

Outcome Measures

Primary Outcomes (1)

• Change of serum anti-dsDNA antibody titers at 24 weeks of treatment vs baseline

  The change of serum anti-dsDNA antibody titers at 24 weeks of treatment compared to baseline will be summarized using descriptive statistics, including mean, standard deviation, median, percentiles and range. The analysis will be performed in the Response evaluable population. Change from baseline will be calculated as post-baseline value minus baseline value. The 95% confidence interval (CI) of the mean change will also be provided. To assess whether the median change from baseline is significantly different from zero, the Wilcoxon Signed-Rank Test will be used. A decrease of approximately 30 IU/mL in 50% of the patients in a JAK1/JAK2 inhibitor trial will be evaluated as significant.

  Assessments while participant is on treatment will be considered. Specifically, available assessments at 24 weeks (+/- 4 weeks) will be considered in the endpoint evaluation. If multiple assessments are included in the specified time window, the one that

Secondary Outcomes (4)

• The safety and tolerability profile of belantamab mafodotin in patients with SLE

  Changes from baseline until at least 1 dose of belantamab mafodotin (Cycle 1, Day 1).

• The effect of belantamab mafodotin on SLE serology on additional timepoints of treatment.

  Assessments while participant is on treatment will be considered. Specifically, available assessments at 12, 36, 48 weeks and end of trial (EOT) (+/- 4 weeks) will be considered in the endpoint evaluation.

• The effect of belantamab mafodotin on SLE clinical endpoints and resolution of SLE symptoms.

  Assessments while participant is on treatment will be considered. Specifically, available assessments at 12, 24, 36, 48, 60, 72 weeks and end of trial (EOT) (+/- 4 weeks) will be considered in the endpoint evaluation.

• The effect of belantamab mafodotin on GC sparing.

  Assessments while participant is on treatment will be considered. Specifically, available assessments at 12, 24, 36, 48, 60, 72 weeks and end of trial (EOT) (+/- 4 weeks) will be considered in the endpoint evaluation.

Study Arms (1)

Single-arm trial, Open-label study, Overall, 12 participants will be enrolled in the trial.

OTHER

Non-randomized, open label assignment, No adaptive design specified, Planned Duration of trial intervention is 36 months. Participants will be treated for a total period of two years per participant or until treatment failure, physician decision, unacceptable toxicity, withdrawal of consent, or death (whichever occurs first). NOTE 1: The start of a Cycle1 D1 of a cycle is defined when Belantamab mafodotin is administered.

Drug: belantamab mafodotin to the existing stable standard background therapy

Interventions

belantamab mafodotin to the existing stable standard background therapy DRUG

Trial treatment is defined as the addition of belantamab mafodotin to the existing stable standard background therapy. Belantamab mafodotin will be added to existing stable background SoC therapy, which can be GC, HCQ, or a single conventional immunosuppressive drug (such as azathioprine, methotrexate, or mycophenolate). For the purposes of this trial, belantamab mafodotin is considered an investigational medicinal product (IMP), while background SoC therapy regimen(s) is(are) considered auxiliary medicinal product(s) (AxMP). Background SoC therapy regimens should be authorized for use in the European Union and/or the country where the trial is taking place, and/or clearly endorsed/recommended by international treatment guidelines, if not otherwise authorized. Belantamab mafodotin is not authorized for use in the European Union.

Single-arm trial, Open-label study, Overall, 12 participants will be enrolled in the trial.

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 SLE classification criteria.
• Age between 18 and 60 years.
• 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.
• Have a positive anti-dsDNA test (enzyme-linked immunosorbent assay \[ELISA\]).
• Active disease, defined by a SLE Disease Activity Index (Safety of Estrogens in Systemic Lupus Erythematosus National Assessment \[SELENA\] SLEDAI score≥ 6, including clinical SLEDAI ≥ 4 (please refer to APPENDIX 5 - SELENA SLEDAI SCORE).
• Demonstrate moderate to severe disease based on SLEDAI-2K score ≥ 6 observed at screening (please refer to APPENDIX 6 - SLEDAI-2K SCORE)
• Failure to, or lack of tolerability of, at least one previous state-of-the-art immunosuppressive drug (does not account for GC).
• Patients with either extra-renal disease or patients with kidney involvement (LN) are eligible. LN patients should be class III, IV, or V (please refer to APPENDIX 8 - LUPUS NEPHRITIS CLASSIFICATION).
• Adequate organ system function as defined by the below laboratory assessments. Hematologic
• Absolute neutrophil count (ANC) ≥1.5 X 109/L; granulocyte colony stimulating factor use within the past 14 days is NOT permitted.
• Hemoglobin ≥8.0 g/dL; transfusions within the past 14 days are NOT permitted. Erythropoietin use is allowed.
• Hepatic
• Total bilirubin ≤1.5xUpper limit of normal (ULN) (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Alanine aminotransferase (ALT) ≤ 2.5xULN. Renal
• a. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2; calculated using the Modified Diet in Renal Disease formula (please refer to APPENDIX 9 - MODIFIED DIET IN RENAL DISEASE (MDRD) FORMULA).

You may not qualify if:

• Participants are excluded from the trial if any of the following criteria apply:
• Severe kidney (rapidly progressive class III or IV glomerulonephritis) or neuropsychiatric SLE (e.g., optic neuritis, transverse myelitis, psychosis, uncontrolled seizures), pulmonary haemorrhage, myocarditis) that is likely to warrant escalation in therapy beyond permitted background medications. Subjects requiring renal haemodialysis or peritoneal dialysis are also excluded.
• Active infection, requiring treatment, and/or serious infection (e.g. sepsis, pneumonia, or pyelonephritis), or history of hospitalization or IV antibiotics receipt for a serious infection during the 3 months prior to consent.
• Latent or active tuberculosis
• Major surgery, (e.g. requiring general anesthesia) within 3 months before screening.
• NOTE 1: The participant must be clinically stable following a major surgery to be entered in the trial.
• NOTE 2: Major surgery shall be defined based on the Investigator's judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcome s.
• Acute illness, including a common cold, within 2 weeks prior to first trial treatment or has had a major illness or hospitalization within 3 months prior to consent.
• Other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis, psoriatic arthritis.
• 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 disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
• Chronic liver disease. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
• Participant has received B cell depleting therapy within 12 months prior to first administration of the trial agent (e.g. RTX, ocrelizumab or obinutuzumab),
• Participant has received a therapy that inhibits B-cell activating factor (BAFF) (i.e. belimumab) within 2 months prior to first administration of the trial agent.
• Participant 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 trial agent.
• Participant has received oral or IV cyclophosphamide within 2 months prior to first administration of the trial agent.

Sponsors & Collaborators

• GlaxoSmithKline: collaborator
• Medical Association for the Study of Cancer Biology and Treatment: lead

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Phase II, Proof Of Concept, Open Label, Study

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 28, 2026
• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): December 1, 2031
• Last Updated: September 28, 2026

Record last verified: 2026-09