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.
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]).
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.
Single group
belantamab mafodotin to the existing stable standard background therapy
DrugTrial 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.
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.
The safety and tolerability profile of belantamab mafodotin in patients with SLE
Treatment emergent AEs and SAEs will be presented by the Medical Dictionary for Regulatory Activities System Organ Class (SOC) and Preferred Term (PT) on Safety population. Specifically, the number (%) of participants experiencing at least one AE and at least one SAE will be presented by each different term (SOC and PT term). If multiple AEs are reported for the same participant under the same PT or SOC, they will be counted once, based on the maximum severity grade. Additionally, frequencies and proportions of participants with abnormal ocular findings (BCVA change from baseline; keratopathy; ocular symptoms) will be presented overall by maximum grade in the Safety population. In addition, frequencies and proportions will also be presented for the number of assessments.
The effect of belantamab mafodotin on SLE serology on additional timepoints of treatment.
The change of serum anti-dsDNA antibody titers at weeks 12, 36, 48 and end of trial (EOT) 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 for each timepoint. To assess whether the median change from baseline is significantly different from zero, the Wilcoxon Signed-Rank Test will be used. If the data distribution permits, a Mixed Model for Repeated Measures (MMRM) will be used to evaluate differences in post-baseline values over time while adjusting for baseline covariates. A spaghetti plot or line plot will be used to visualize individual and overall trends in anti-dsDNA antibody titers over time, displaying changes from baseline to all post-baseline time points.
The effect of belantamab mafodotin on SLE clinical endpoints and resolution of SLE symptoms.
The proportion of participants along with the 95% Confidence Intervals at each specified timepoint will be provided in the Response evaluable population for those who will achieve: * SRI-4 response at weeks 12, 24, 36, 48, 60, 72 and end of trial (EOT) * BICLA response at weeks 12, 24, 36, 48, 60, 72 and end of trial (EOT) * resolution of arthritis or rash at weeks 12, 24, 36, 48 and end of trial (EOT) * at least partial renal response at weeks 12, 24, 36, 48 and end of trial (EOT)
The effect of belantamab mafodotin on GC sparing.
The number and proportion of participants with successful tapering of GC at weeks 12, 24, 36, 48, 60, 72 and end of trial (EOT) will be presented in Response evaluable population.
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Medical Association for the Study of Cancer Biology and Treatment
Lead sponsor
GlaxoSmithKline
Collaborator
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