iptacopan hydrochloride for Lupus nephritis | Lupus Nephritis Class III-IV, +/- V

Inclusion criteria

• {"criterion_text":"- Male and female patients ≥ 18 years of age or older at the time of screening\n- Vaccination against Haemophilus influenzae is recommended, according to local guidelines, at least 2 weeks before treatment with iptacopan is initiated\n- 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.\n- All patients should have been on supportive care including stable dose regimen of anti-malarials (e.g. hydroxychloroquine) unless contraindicated\n- 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\n- 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\n- Participants should have a negative COVID-19 test result at screening (performed as per local SoC). Vaccination against COVID-19 should follow local SoC.\n- 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\n- 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\n- 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: \t● Positive dipstick for hematuria (not associated with menstruation or UTI) \t● 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\n- 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)"}

Exclusion criteria

• {"criterion_text":"- Participants who in the opinion of the investigator have previously failed to respond to therapy with MMF/MPS will not be included\n- 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.\n- Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to screening\n- 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\n- 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\n- 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\n- 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\n- Prior treatment with any of the following within 1 year prior to screening: •\tNitrogen mustard, chlorambucil, vincristine, procarbazine, etoposide, abatacept •\tTreatment with any B-cell targeted therapy •\tTreatment with biological investigational agent •\tTreatment with interleukin-6 targeted therapy\n- 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"}

Primary endpoints

• {"endpoint_text":"- Part 1 and 2: Proportion of patients achieving Complete Renal Response (CRR) at week 24 in the absence of renal flares","definition_or_measurement_approach":"CRR at week 24 is defined and assessed based on the Urine Protein-To-Creatinine Ratio (UPCR) value from 24 hour urine samples and evaluated in the absence of renal flares; primary objective text specifies comparison of proportions achieving CRR at week 24 based on UPCR from 24-hour urine samples and absence of renal flares, assessed regardless of treatment discontinuations and as if rescue corticosteroids for reasons other than renal flares had not been administered."}

Secondary endpoints

• {"endpoint_text":"- Parts 1 and 2: Proportion of patients achieving CRR or PRR in the absence of renal flares at weeks 24 and 52","definition_or_measurement_approach":"Proportion achieving Complete Renal Response (CRR) or Partial Renal Response (PRR) at weeks 24 and 52 in the absence of renal flares; timepoints specified (weeks 24 and 52)."}
• {"endpoint_text":"- Time-to-Complete Renal Response (CRR) based on first morning void (FMV) urine samples","definition_or_measurement_approach":"Time-to-event endpoint using first morning void (FMV) urine samples to determine time to CRR."}
• {"endpoint_text":"- Proportion of patients achieving ≥25% UPCR reduction in the absence of renal flares compared to baseline at week 24","definition_or_measurement_approach":"Proportion achieving ≥25% reduction in 24h UPCR from baseline at week 24 in absence of renal flares."}
• {"endpoint_text":"- Frequency of courses of corticosteroids for renal and non-renal indications at a dose exceeding an average of 20mg/day (of prednisolone or equivalent) for more than 10 days between weeks 24 and 52","definition_or_measurement_approach":"Frequency/count of corticosteroid courses (prednisolone equivalent) exceeding an average of 20 mg/day for >10 days between weeks 24 and 52, for renal and non-renal indications."}
• {"endpoint_text":"- Change from baseline FACIT-Fatigue Score at weeks 24 and 52","definition_or_measurement_approach":"Change from baseline in FACIT-Fatigue questionnaire score at weeks 24 and 52."}
• {"endpoint_text":"- Change from baseline in SLEDAI-2K score at weeks 24 and 52","definition_or_measurement_approach":"Change from baseline in SLEDAI-2K disease activity score at weeks 24 and 52."}
• {"endpoint_text":"- Change from baseline in BILAG-2004 score at weeks 24 and 52","definition_or_measurement_approach":"Change from baseline in BILAG-2004 clinical index at weeks 24 and 52."}
• {"endpoint_text":"- Safety endpoints up to week 52 for Part 1 and 2","definition_or_measurement_approach":"Safety assessments including adverse events and other standard safety measures up to week 52."}
• {"endpoint_text":"- Log-transformed ratio to baseline of 24h UPCR at week 24","definition_or_measurement_approach":"Analysis of log-transformed ratio of 24h UPCR to baseline at week 24 to evaluate dose-exposure response."}

Germany

Latest Decision Or Authorization Date

25-07-2024

Number Of Sites

6

Number Of Participants

12

France

Latest Decision Or Authorization Date

13-08-2024

Number Of Sites

4

Number Of Participants

7

Hungary

Latest Decision Or Authorization Date

17-07-2024

Number Of Sites

3

Number Of Participants

12

Spain

Latest Decision Or Authorization Date

15-07-2024

Number Of Sites

7

Number Of Participants

7

Portugal

Latest Decision Or Authorization Date

17-07-2024

Number Of Sites

4

Number Of Participants

10

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Responsibilities

codes: 13; 15: Medical Data Review

Name

Icon Clinical Research Limited

Responsibilities

code: 1

Name

Veeda Clinical Research Limited

Responsibilities

code: 15: Pharmacokinetics analysis

Name

Syneos Health Inc.

Responsibilities

code: 1

Name

Parexel International (IRL) Limited

Responsibilities

code: 12

Third parties

• {"country":"France","full_name":"SGS France","duties_or_roles":"Biomarker samples analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 13; 15: Medical Data Review","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"code: 15: Pharmacokinetics analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Kayentis","duties_or_roles":"code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"code: 12","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"code: 15: PRO licensing, formatting and translations","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinical Ink Inc.","duties_or_roles":"code: 7","organisation_type":"Pharmaceutical company"}