NCT04558918

Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment

A Randomized, Multicenter, Active-comparator Controlled, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult Patients With PNH and Residual Anemia, Despite Treatment With an Intravenous Anti-C5 Antibody.

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 97 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study was a multi-center, randomized, open-label, active comparator-controlled, parallel group study. The purpose of this Phase 3 study in PNH patients presenting with residual anemia despite treatment with anti-C5 antibody, was to determine whether iptacopan is efficacious and safe for the treatment of PNH through demonstration of superiority of iptacopan compared to anti-C5 antibody treatment.

Detailed description

The study comprised three periods: * A screening period lasting up to 8 weeks (unless there was a need to extend it for vaccinations required for inclusion, vaccinations were started as early as possible to avoid extension of the screening period) * A 24-week randomized, open-label, active controlled, treatment period for the primary efficacy and safety analyses. Patients who met the eligibility criteria at screening were stratified based on the type of prior anti-C5 antibody treatment (eculizumab or ravulizumab) and based on the transfusion history as reported during the last 6 months prior to randomization (i.e. transfusion received/not received). Patients were randomized to one of the two treatment groups in an 8:5 ratio to either iptacopan monotherapy at a dose of 200 mg orally b.i.d. or i.v. anti-C5 antibody treatment (patients continued with the same regimen during the randomized treatment period as they were prior to randomization), respectively. * A 24-week open-label, iptacopan treatment extension period. The patients randomized to the active comparator group were offered to switch to iptacopan on Day 168 (Week 24 visit) and entered the treatment extension period, after receiving a last dose of anti-C5 antibody treatment (eculizumab or ravulizumab). For patients in the comparator group not agreeing to switch treatment, Week 24 visit was the End of Study visit for the trial with no participation in the treatment extension period. For patients agreeing to switch to oral iptacopan, the Extension treatment started on the day after completion of the Week 24 visit. The patients in the iptacopan group who, in the opinion of investigator, benefitted from treatment and were taking iptacopan at Week 24 visit (i.e. did not permanently discontinue study medication), were offered the opportunity to continue oral iptacopan treatment during the treatment extension period. * Data cut-off date used for the primary results submission was 26- Sep-2022

Conditions

• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Interventions

Type	Name	Description
DRUG	LNP023	Taken Orally b.i.d. Dosage Supplied: 200 mg Dosage form: Hard gelatin capsule Route of Administration: Oral
DRUG	Eculizumab	Administered as intravenous infusion every 2 weeks as per the stable regimen, the maintenance dose is a fixed dose. Dosage Supplied: 300 mg/30mL Dosage form: Concentrate solution for infusion
DRUG	Ravulizumab	Administered as intravenous infusion every 8 weeks, the maintenance dose is based on body weight. Dosage Supplied: 300 mg/30mL Dosage form: Concentrate solution for infusion

Timeline

• Start date: 2021-01-25
• Primary completion: 2022-09-26
• Completion: 2023-03-06
• First posted: 2020-09-22
• Last updated: 2024-10-09
• Results posted: 2023-11-28

Locations

39 sites across 12 countries: United States, Brazil, Czechia, France, Germany, Italy, Japan, Netherlands, South Korea, Spain, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study