Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy. (APPEAR-C3G)
Actively Recruiting
About This Study
This Phase 3, multicenter, randomized, double-blind trial evaluates the efficacy and safety of iptacopan, an oral complement alternative pathway inhibitor, in adult and adolescent patients with native C3 glomerulopathy. Participants are randomized to receive either iptacopan or placebo in addition to standard of care to assess the drug's impact on proteinuria and renal function. The primary endpoints include the reduction in UPCR and stabilization of eGFR compared to placebo at the end of the treatment period. Secondary objectives utilize serum C3 levels and repeat kidney biopsies to evaluate the inhibition of the alternative pathway and associated histopathological improvements.
Who Can Participate?
✓ Inclusion Criteria
- •Male and female participants age ≥ 12 and ≤ 60 years at screening.
- •Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment in adults and within 3 years in adolescents.
- •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 acid, 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 ages ≥ 18 years and modified Schwartz formula for ages 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15.
- •Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae prior to the start of study treatment.
- •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.
✗ Exclusion Criteria
- •Participants who have received any cell or organ transplantation, including a 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., N. meningitidis and S. pneumoniae.
- •The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti 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.
- •Acute post-infectious glomerulonephritis at screening based upon the opinion of the investigator.