Clinical trial NCT04820530: Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
Official title: A Multicenter, Single-arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: Paroxysmal nocturnal hemoglobinuria
Hemoglobin
Anemia
LNP023
Iptacopan
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions
timeFrame: Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168
Secondary outcomes:
measure: Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions
timeFrame: Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168
measure: Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions
timeFrame: Between Day 14 and Day 168
measure: Change From Baseline in Hemoglobin Levels in the Core Treatment Period
timeFrame: Baseline, Day 126 to 168
measure: Percent Change From Baseline in LDH
timeFrame: Baseline, Day 126 to 168
measure: Adjusted Annualized Clinical BTH Rate in the Core Treatment Period
timeFrame: Between Day 1 and Day 168
measure: Change From Baseline in Absolute Reticulocyte Count
timeFrame: Baseline and mean of visits between Day 126 and 168
measure: Change From Baseline in FACIT-Fatigue Score
timeFrame: Baseline and mean of visits between Day 126 and Day 168
measure: Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period
timeFrame: Between Day 1 and Day 168
Other outcomes:
measure: Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions
timeFrame: Baseline, Day 336
measure: Marginal Proportion (Expressed as Percentage) of Patients Not Receiving and Not Requiring RBC Transfusions
timeFrame: Between Day 14 and Day 336
measure: Change From Baseline in Hemoglobin Levels
timeFrame: Baseline, Day 336
measure: Change From Baseline in LDH at Visit Day 336
timeFrame: Baseline, Day 336
measure: Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment
timeFrame: Between Day 1 and Day 336
measure: Change From Baseline in Absolute Reticulocyte Count at Day 336
timeFrame: Baseline, Day 336
measure: Change From Baseline in FACIT-Fatigue Score
timeFrame: Baseline, Day 336
measure: Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment
timeFrame: Between Day 1 and Day 336
Locations:
city: Beijing
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Paris 10
country: France
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Avellino
country: Italy
facility: Novartis Investigative Site
state: AV
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Kota Kinabalu
country: Malaysia
facility: Novartis Investigative Site
state: Sabah
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: