Study of efficacy and safety of LNP023 in participants with active lupus nephritis Class III-IV, +/- V

Korábbi kezelés

• Participants who in the opinion of the investigator have previously failed to respond to therapy with MMF/MPS will not be included
• Induction treatment with cyclophosphamide within 3 months of planned treatment for this study; treatment with calcineurin inhibitors within the previous 3 months prior to randomization.
• Renal biopsy presenting with interstitial fibrosis/tubular atrophy (IF/TA) or glomerulosclerosis of more than 50% based on chronicity index score (Bajema et. al s 2018), or which in the opinion of the investigator is such that it precludes likely response to immunosuppressive therapy. Patients previously treated with immunosuppressive or other immunomodulatory agents which are not considered standard of care for treatment of lupus nephritis within the previous 1 year
• Participants being treated with systemic corticosteroids (>5 mg/day prednisone or equivalent) for indications other than SLE or LN e.g. acute asthma, inflammatory bowel disease
• Participants being treated with systemic corticosteroids for SLE or LN will be excluded if they have taken more than an average of 15 mg/day prednisone (or equivalent) in the previous 4 weeks and more than an average of 30 mg/day in the 1 week prior to randomization
• For participants with renal biopsy confirming Class III or IV lupus nephritis (+/- class V) more than 2 months prior to screening: receipt of more than a total dose of 1000 mg equivalent IV pulse methylprednisolone (cumulative dose) within 2 weeks prior to randomization
• Prior treatment with any of the following within 1 year prior to screening: • Nitrogen mustard, chlorambucil, vincristine, procarbazine, etoposide, abatacept • Treatment with any B-cell targeted therapy • Treatment with biological investigational agent • Treatment with interleukin-6 targeted therapy

Laborértékek

• Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to screening
• Participants with current clinical, radiographic, or laboratory evidence of active or latent TB; history of active TB within 2 years of screening (even if treated); in the opinion of the investigator and based on appropriate evaluation, have a risk of reactivation of TB that precludes the use of conventional immunosuppression

• Male and female patients ≥ 18 years of age or older at the time of screening
• Vaccination against Haemophilus influenzae is recommended, according to local guidelines, at least 2 weeks before treatment with iptacopan is initiated
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment is expected to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
• All patients should have been on supportive care including stable dose regimen of anti-malarials (e.g. hydroxychloroquine) unless contraindicated
• Patients should be receiving stable optimized ACEi or ARB therapy at either locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgement) at randomization as per the local clinical practice. The dose of ACEi / ARB therapy should remain stable throughout the study unless there is a clinically important indication to change this e.g. the development of adverse events or sub-optimally controlled hypertension
• Patients with first presentation or flare of lupus nephritis can be included. All participants with a LN flare, following prior treatment with cyclophosphamide can be included. Participants who have developed a LN flare following treatment with MMF may be included if the treating physician is of the opinion that participation in the study is of potential benefit to the patient, considering the doses of MMF with or without corticosteroids being used in the study protocol
• Participants should have a negative COVID-19 test result at screening (performed as per local SoC). Vaccination against COVID-19 should follow local SoC.
• Unequivocally positive anti-nucleosome antibodies (ANA) test result defined as an ANA titre ≥1:80 (based on HEp-2 immunofluorescence assay or an equivalent positive enzyme immunoassay) and/or a positive anti dsDNA at screening
• Active biopsy-proven lupus nephritis within 3 months prior to screening demonstrating Class III or IV lupus nephritis with or without co-existing features of Class V lupus nephritis. If a biopsy was not performed within 3 months of screening, a repeat biopsy is needed to verify LN as a main cause of flare. This renal biopsy will need to be performed during the screening period and after confirmation that the patient has met all other inclusion/exclusion criteria at screening
• Documentation of active renal disease at the time of screening necessitating the commencement of therapy with corticosteroids in combination with MMF/MPS. Active renal disease will be defined by the following: ● Positive dipstick for hematuria (not associated with menstruation or UTI) ● Proteinuria (to be confirmed at screening and prior to randomization) At screening: UPCR of ≥ 1.5 g/g sampled from a first morning void or 24 hour urine collection Prior to randomization: Confirmation of UPCR ≥ 1.5 g/g sampled from a 24 hour urine collection on two separate days, within a window of 10 days prior to randomization. The calculation of the (arithmetic) mean of the UPCR values obtained from the two 24h urine collections will be used to confirm eligibility
• eGFR ≥ 30 ml/min/1.73 m2 (eGFR calculated using the CKD-EPI formula or modified MDRD formula according to specific ethnic groups and local practice guidelines)