Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (APPOINT-PNH)

Novartis

Status and phase

Completed

Phase 3

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Treatments

Drug: Iptacopan (LNP023)

Study type

Interventional

Funder types

Industry

Identifiers

NCT04820530

CLNP023C12301

2020-003172-41 (EudraCT Number)

Details and patient eligibility

About

The purpose of this Phase 3 study was to determine whether iptacopan is efficacious and safe for the treatment of Paroxysmal nocturnal hemoglobinuria (PNH) patients who were naïve to complement inhibitor therapy.

Full description

This study was a multicenter, single-arm, open-label trial which was comprised of 8 weeks screening period, 24-week core treatment period and 24-week extension treatment period.

Eligible PNH patients with hemolysis (LDH > 1.5 ULN) and anemia (hemoglobin <10 g/dL), who were naive to complement inhibitor therapy, including anti-C5 antibody treatment, received iptacopan monotherapy at a dose 200 mg orally b.i.d.

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with RBCs and WBCs clone size ≥ 10%
Mean hemoglobin level <10 g/dL
LDH > 1.5 x Upper Limit of Normal (ULN)
Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment
If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given

Exclusion criteria

Prior treatment with a complement inhibitor, including anti-C5 antibody
Known or suspected hereditary complement deficiency
History of hematopoietic stem cell transplantation
Patients with laboratory evidence of bone marrow failure (reticulocytes <100x109/L; platelets <30x109/L; neutrophils <0.5x109/L).
Active systemic bacterial, viral (incl. COVID-19)or fungal infection within 14 days prior to study drug administration.
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., dialysis), advanced cardiac disease (e.g., NYHA class IV heart failure), 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.