Study of efficacy and safety of iptacopan in complement 3 glomerulopathy patients
- Conditions
- complement 3 glomerulopathyMedDRA version: 20.0Level: PTClassification code 10077827Term: C3 glomerulopathySystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2020-004589-21-ES
- Lead Sponsor
- ovartis Farmacéutica S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 68
- Male and female participants age >/= 18 and -Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment
- 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) or measured GFR >/= 30 ml/min/1.73m2 at Screening and Day -15.
- Vaccination against Neisseria meningitidis infection prior to the start of study treatment. Vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given, if available and according to local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
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
- 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., N. meningitidis and S. pneumoniae.
- 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria.;Primary end point(s): Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection);Timepoint(s) of evaluation of this end point: 6 months;Secondary Objective: - To demonstrate the superiority of iptacopan vs. placebo in improving eGFR.<br>- To demonstrate the superiority of iptacopan vs. placebo in the proportion of participants who achieved a composite renal endpoint.<br>- To demonstrate the effect of iptacopan vs placebo in reducing glomerular inflammation in the kidney.<br>- To assess the effect of iptacopan compared to placebo in improvement of patient reported fatigue.<br>- To evaluate the safety and tolerability of iptacopan compared to placebo
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change from baseline in eGFR <br>- 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. <br>- Change from baseline in disease total activity score in a renal biopsy.<br>- Change in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT Fatigue) score.<br>- 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.;Timepoint(s) of evaluation of this end point: 6 months