A multicenter, randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of Iptacopan (LNP023) in C3 glomerulopathy

Argentina, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, India, Israel, Italy, Japan, Netherlands, Spain, Switzerland, Turkey, United Kingdom, United States (ICTRP)

Identifiant de l'essai ICTRP
NCT04817618 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
A multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in complement 3 glomerulopathy (BASEC)

Titre académique
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Iptacopan (LNP023) in Complement 3 Glomerulopathy. (ICTRP)

Titre public
Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy. (ICTRP)

Maladie en cours d'investigation
C3G (ICTRP)

Intervention étudiée
Drug: PlaceboDrug: iptacopan (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator). (ICTRP)

Critères d'inclusion/exclusion
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 = 38C (100.4F) 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. (ICTRP)

non disponible

Critères d'évaluation principaux et secondaires
Adult cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection);Adolescent cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection);Change from baseline in log-transformed UPCR at the 12-month visit (both study treatment arms).;Change in log-transformed UPCR from the 6-month visit to the 12-month visit in the placebo arm (ICTRP)

Change from baseline in eGFR.;Proportion of participants who meet the criteria for achieving a composite renal endpoint;Adult cohort: Change from baseline in disease total activity score in a renal biopsy.;Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.;Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements;Number of participants with study drug discontinuation due to an AE;Proportion of participants who meet the criteria for achieving a composite renal endpoint;Proportion of patients achieving a composite renal endpoint from the 6-month visit to the 12-month visit of the placebo arm;Change from baseline in the total activity score in a renal biopsy at 12 months;Change in the total activity score in a renal biopsy from the 6-month visit to the 12-month visit of the placebo arm.;Change from baseline in the FACIT-Fatigue score at 12 months;Change in the FACIT-Fatigue score from the 6-month visit to the 12-month visit of the placebo arm;Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements;Number of participants with study drug discontinuation due to an AE (ICTRP)

Date d'enregistrement
non disponible

Inclusion du premier participant
non disponible

Sponsors secondaires
non disponible

Contacts supplémentaires
Novartis Pharmaceuticals;Novartis Pharmaceuticals, novartis.email@novartis.com, 1-888-669-6682, Novartis Pharmaceuticals, (ICTRP)

ID secondaires
2020-004589-21, CLNP023B12301 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT04817618 (ICTRP)