Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.

Novartis Pharmaceuticals52 enrolled

Overview

The purpose of the study was to find out if iptacopan is effective and safe in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who switched from their current standard of care treatment (eculizumab or ravulizumab) to study treatment, iptacopan/LNP023.

This was a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients. This study was comprised of two periods: * A Screening period lasting up to 8 weeks. * A 24-week open-label, iptacopan Treatment period. After completion of the treatment period, participants who continued to benefit from the iptacopan treatment based on the study doctor's evaluation were able to join the Roll-over extension study (CLNP023C12001B).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Interventions

IptacopanDRUG

Treatment with iptacopan at a dose of 200 mg b.i.d. will start on the first day (Day 1) and continue for 24 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. * Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician. * Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening * Mean hemoglobin level ≥10 g/dL * Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment. * If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations. * Ability to communicate well with the investigator, to understand and comply with the requirements of the study * Other protocol -defined inclusion criteria may apply at the end. Exclusion Criteria: * Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment * Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening * History of stem cell transplantation or any solid organ transplantation * Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration * Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration * Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening) * A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus * Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening. * History of cancer of any part of the body within the past 5 years, * Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial. * Any medical condition deemed likely to interfere with the patient's participation in the study * Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study

Locations (23)

City Of Hope National Med Center

Duarte, California, United States

Outcomes

Primary Outcomes

Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority

Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare). Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ \<= -1, H1: μ \> -1.

Time frame: Baseline, Day 126 to Day 168

Secondary Outcomes

Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Superiority

Time frame: Baseline, Day 126 to Day 168

Proportion of Hematological Responders to Iptacopan Treatment

Response defined as Hb ≥12 g/dL assessed between visits Day 126 and Day 168 in the absence of RBC transfusions, on three out of four measurements taken at the visits occurring in last six weeks

Time frame: Day 126 to Day 168

Proportion of Participants Who Remain Free From Transfusions

Number of participants with absence of administration of packed RBC transfusions between Day 1 and Day 168

Data from ClinicalTrials.gov

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