Phase 3 N=97 Randomized Treatment

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

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Bottom Line

View on ClinicalTrials.gov: NCT04558918 ↗

Enrolled (actual)

Serious AEs

12.9%

Results posted

Nov 2023

Primary outcome: Primary: Marginal Proportion (Expressed as Percentages) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions — 82.3; 2.0 Percentage of responders — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: LNP023 (Drug); Eculizumab (Drug); Ravulizumab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Novartis Pharmaceuticals
Primary completion: Sep 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Marginal Proportion (Expressed as Percentages) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions	82.3; 2.0	<0.0001 sig
PRIMARY Marginal Proportion (Expressed as Percentages) of Participants With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions	68.8; 1.8	<0.0001 sig
PRIMARY Percentage of Patients Meeting Hematological Response Criterion After the Start of LNP023 Treatment	86.4; 72.4; 67.8; 58.6	—
PRIMARY Number of Patients Not Requiring RBC Transfusions After the Start of LNP023 Treatment	51; 31; 57; 32	—
PRIMARY Change From Baseline in Hemoglobin at Visit Day 336	3.35; 3.36	—
PRIMARY Change From Baseline in FACIT-Fatigue Questionnaire at Day 336	9.80; 10.96	—
PRIMARY Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment	0.11	—
PRIMARY Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment	0.04	—
SECONDARY Marginal Proportion (Expressed as Percentages) of Participants Who Remain Free From Transfusions	94.8; 25.9	<0.0001 sig
SECONDARY Change From Baseline in Hemoglobin Between Day 126 and 168	3.60; -0.06	<0.0001 sig
SECONDARY Change From Baseline in FACIT-Fatigue Questionnaire in the Randomized Treatment Period	8.59; 0.31	<0.0001 sig
SECONDARY Change From Baseline in Absolute Reticulocyte Count in the Randomized Treatment Period	-115.81; 0.34	<0.0001 sig
SECONDARY Ratio to Baseline in Log-transformed LDH in the Randomized Treatment Period	0.96; 0.98	0.8361
SECONDARY Adjusted Annualized Clinical BTH Rate in the Randomized Treatment Period	0.07; 0.67	0.01183 sig
SECONDARY Adjusted Annualized Major Adverse Vascular Events Rate in the Randomized Treatment Period	0.03; 0.00	0.31731

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.

Eligibility Criteria

Inclusion Criteria

Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with clone size ≥ 10%
Stable regimen of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to randomization
Mean hemoglobin level <10 g/dL
Vaccination against Neisseria meningitidis infection is required prior to the start of treatment.
If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given

Exclusion Criteria

Participants on a stable eculizumab dose but with a dosing interval of 11 days or less or patients on stable ravulizumab dose but with a dosing interval of less than 8 weeks.
Known or suspected hereditary complement deficiency at screening
History of hematopoietic stem cell transplantation
Patients with laboratory evidence of bone marrow failure (reticulocytes <100x10E9/L; platelets <30x10E9/L; neutrophils <500x10E6/L).
Active systemic bacterial, viral (incl. COVID-19), or fungal infection within 14 days prior to study drug administration
A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus.
Major concurrent comorbidities including but not limited to severe kidney disease (e.g., eGFR < 30 mL/min/1.73 m2, dialysis), advanced cardiac disease (e.g., NYHA class IV), severe pulmonary disease (e.g., severe pulmonary hypertension (WHO class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04558918). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.