complement 3 glomerulopathy MedDRA version: 20.0 Level: PT Classification code 10077827 Term: C3 glomerulopathy System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: iptacopan
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Iptacopan
Current Sponsor code: LNP023
Other descriptive name: Iptacopan hydrochloride
Concentratio
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male and female participants age = 18 and = 60 years (adult cohort) or age = 12 and = 17 years (adolescent cohort) at screening. -Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment in adults and within 3 years of enrollment in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available, confirmation may be obtained using tissue from the Day -45 biopsy (adults only) for local assessment (tissue may be processed, evaluated, and reported by Arkana Laboratories but eligibility is determined by the Investigator). - Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for at least 90 days. The doses of other antiproteinuric medications including mycophenolic acids, corticosteroids, and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization. - Reduced serum C3 (defined as less than 0.85 x lower limit of the central laboratory normal range) at Screening. - UPCR = 1.0 g/g sampled from the first morning void urine sample at Day -75 and Day -15. - Estimated GFR (using the CKD-EPI formula for adults and modified Schwartz formula for adolescents) or measured GFR = 30 ml/min/1.73m2 at Screening and Day -15. - Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated. - If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated. Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 68 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Participants who have received any cell or organ transplantation, including kidney transplantation. - Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with renal biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli. - Renal biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%. - Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care. - Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration. - The presence of fever = 38°C (100.4°F) within 7 days prior to study treatment administration. - A history of recurrent invasive infections caused by encapsulated organisms, e.g., meningococcus or pneumococcus. - The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti Complement 5 (C5) antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit. - The use of immunosuppressants (except mycophenolic acids), cyclophosphamide or systemic corticosteroids at a dose >7.5 mg/day (or equivalent for a similar medication) within 90 days of study drug administration. The use of mycophenolic acids is not permitted within 90 days prior to randomization in India. - Acute post-infectious glomerulonephritis at screening based upon the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective in adult participants: To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria. Primary objective in adolescent participants: To evaluate the effect of iptacopan on proteinuria.;Secondary Objective: Secondary objectives for adult participants: - To demonstrate the superiority of iptacopan vs. placebo in improving eGFR. - To demonstrate the superiority of iptacopan vs. placebo in the proportion of participants who achieved a composite renal endpoint. - To demonstrate the effect of iptacopan vs placebo in reducing glomerular inflammation in the kidney. - To assess the effect of iptacopan compared to placebo in improvement of patient reported fatigue. - To evaluate the safety and tolerability of iptacopan compared to placebo. Secondary objectives in adolescent participants: - To evaluate the effect of iptacopan in improving eGFR. - To evaluate the effect of iptacopan on a composite renal endpoint. - To evaluate the effect of iptacopan in improvement of patient-reported fatigue. - To evaluate the safety and tolerability of iptacopan compared to placebo during the 6-month double-blind period. ;Primary end point(s): Primary endpoint for adult participants: - Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) Primary endpoint for adolescent participants: - Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection).;Timepoint(s) of evaluation of this end point: Timepoint of evaluation for the primary endpoint for adult participants: - 6 months Timepoint of evaluation for the primary endpoint for adolescent participants: - 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint(s) for adult participants: - Change from baseline in eGFR - A participant meets the requirements of the composite renal endpoint if he/she satisfies: (1) a stable or improved eGFR compared to the baseline visit (=15% reduction in eGFR), and (2) a =50% reduction in UPCR compared to the baseline visit. Initiation of treatment with any complement pathway modifying agent or initiation/intensification of corticosteroid or immunosuppressant or renal replacement therapy automatically designates the participant as not meeting the endpoint. - Change from baseline in disease total activity score in a renal biopsy. - Change in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT Fatigue) score. - Occurrence of clinically significant vital signs, ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE. Secondary endpoint(s) for adolescent participants: - Change from baseline in eGFR - A participant meets the requirements of the composite renal endpoint if he/she satisfies the following criteria at the 6 month time point: (1) a stable or improved eGFR compared to the baseline visit (=15% reduction in eGFR), and (2) a =50% reduction in UPCR compared to the baseline visit. Initiation of treatment with any complement pathway modifying agent or initiation/intensification of corticosteroid or immunosuppressant or renal replacement therapy automatically designates the participant as not meeting the endpoint. - Change from baseline to 6 months in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score. - Occurrence of clinically significant vital signs, ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue) during the doubleblind period of the study.;Timepoint(s) of evaluation of this end point: Timepoin | — |
Countries
Argentina, Belgium, Brazil, Canada, China, Czechia, Czech Republic, France, Germany, Greece, India, Israel, Italy, Japan, Netherlands, Slovakia, Spain, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed