A Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan/LNP023 in Participants With Primary IgA Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety and tolerability, of open label iptacopan in primary IgA nephropathy participants who have completed either the CLNP023X2203 or CLNP023A2301 clinical trials. The open-label design of the current study is appropriate to provide study participants the opportunity to receive treatment with iptacopan until marketing authorizations are received and the drug product becomes commercially available while enabling collection of long-term safety and tolerability data for the investigational drug. Furthermore efficacy assessments conducted every 6 months will afford the opportunity to evaluate the clinical effects of iptacopan on long-term disease progression.

Detailed Description
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This is an open-label, non-randomized, multicenter roll-over extension program (REP) to: CLNP023X2203, a Phase II trial investigating the dose ranging effects of LNP023 on efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability in primary IgAN patients, and CLNP023A2301, a Phase III trial, investigating the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of LNP023 in patients with primary IgAN. Subjects completing the CLNP023X2203 and CLNP023A2301 trials on study drug, who want to continue treatment and who meet the inclusion/exclusion requirements of the roll over extension program, will have the opportunity to receive iptacopan until: 3 years from LPFV of this study CLNP023A2002B, or the participant no longer derives benefit from iptacopan according to the Investigator, or the benefit-risk profile of the product in IgAN is no longer positive, or initiation of maintenance hemodialysis, kidney transplantation or eGFR < 15 mL/min/1.73m2 , or the product becomes commercially available in a specific country following product launch and subsequent reimbursement for IgAN, where applicable, or if a marketing application or reimbursement of an investigational product is rejected/not pursued in a region/country for the indication under study or which ever is sooner

Official Title
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A Multicenter Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan in Adult Participants With Primary IgA Nephropathy Who Have Completed Study CLNP023X2203 or CLNP023A2301

Conditions
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Primary IgA Nephropathy

Intervention / Treatment
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* Drug: LNP023


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For LNP023X2203, participants must have completed part 1 or part 2 of the trial. For LNP023A2301, participants must have completed the entire core trial defined as the full 24 month treatment period. eGFR* ≥ 20 ml/min/1.73m2 *eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines) Per investigator's clinical judgement, the participant may benefit from receiving the open-label treatment of iptacopan 200 mg b.i.d. Prior Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e. any boosters required administered according to local regulations. All participants must be on supportive care regimen of ACEi or ARB* as per KDIGO guidelines. participants who are not taking KDIGO guideline doses because they have documented allergies or intolerance to ACEi and ARB are eligible for the study Exclusion Criteria: participants who screen or baseline failed in the CLNP023X2203 Part 1 or Part 2, or CLNP023A2301 studies or who prematurely withdrew from either study for any reason. Evidence of severe urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before dosing with LNP023. Current (within 4 weeks of study drug administration in the REP) acute kidney injury (AKI) Presence of Rapidly Progressive Glomerulonephritis (RPGN) as defined by 50% decline in eGFR within the last 3 months. Participants treated with immunosuppressive or other immunmodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus and/or systemic corticosteroids exposure (>7.5 mg/d prednisone/prednisolone equivalent) within 5 half-lives of respective medication or 90 days prior to first study drug administration, whichever is shorter. Rituximab requires 180 days wash out. Use of other investigational drugs at the time of enrolment, or within 5 half-lives of enrolment or within 30 days whichever is longer. History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LNP023<br>All participants are receiving 200 mg b.i.d | Drug: LNP023<br>* Capsule 200 mg (b.i.d.) taken orally twice a day<br>* Other names: iptacopan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of participants with serious adverse event | Summary statistics on serious adverse events | Date of first administration of (Day 1) to 7 days after the date of the last actual administration of study treatment | 
| Number and percentage of participants with adverse event | Summary statistics on adverse events | Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment | 
| Number and percentage of participants with adverse events of special interest | Summary statistics on adverse events of special interest | Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual adminstration of study treatment | 
| Number and percentage of participants with abnormalities in vital signs | Summary statistics on abnormalities in vital sign parameters | Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment | 
| Number and percentage of participants with abnormalities in ECG | Summary statistics in abnormalities in ECG parameters | Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment | 
| Number and percentage of participants with abnormalities in clinical laboratory evaluations | Summary statistics on abnormalities in clinical laboratory evaluations | Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized total eGFR slope | Annualized rate of renal disease progression as measured by mean eGFR slope at post baseline visits | Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter | 
| Change from baseline in eGFR | Average change from baseline in eGFR at post-baseline visits | Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter | 
| Log transformed ratio to baseline in UPCR, UACR | Log transformed ratio to baseline in UPCR, UACR at post-baseline visits. The log transformation refers to the natural log (base on e) | Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoglobulin A nephropathy, Primary IgA nephropathy, IgAN, chronic kidney disease, glomerulonephritis, complement alternative pathway, eGFR, UPCR, UACR, LNP023