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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 16 February 2021
Main ID:  NCT04558918
Date of registration: 27/08/2020
Prospective Registration: Yes
Primary sponsor: Novartis Pharmaceuticals
Public title: Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment APPLY-PNH
Scientific title: 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.
Date of first enrolment: January 25, 2021
Target sample size: 91
Recruitment status: Recruiting
URL:  https://clinicaltrials.gov/show/NCT04558918
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 3
Countries of recruitment
Netherlands
Contacts
Name:     Novartis Pharmaceuticals
Address: 
Telephone: 1-888-669-6682
Email: novartis.email@novartis.com
Affiliation: 
Name:     Novartis Pharmaceuticals
Address: 
Telephone:
Email:
Affiliation:  Novartis Pharmaceuticals
Key inclusion & exclusion 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

- 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 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., 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.

Other protocol-defined inclusion/exclusion criteria may apply



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention(s)
Drug: Eculizumab
Drug: LNP023
Drug: Ravulizumab
Primary Outcome(s)
Percentage of participants achieving a sustained increase in hemoglobin levels of = 2 g/dL in the absence of red blood cell transfusions [Time Frame: Day 168]
Percentage of participants achieving sustained hemoglobin levels = 12 g/dL in the absence of red blood cell transfusions [Time Frame: Day 168]
Secondary Outcome(s)
Average change in hemoglobin [Time Frame: Baseline and as mean of visit Day 126, 140, 154 and 168]
Average change in reticulocyte counts [Time Frame: Baseline and as mean of visit Day 126, 140, 154 and 168]
Average percent change in LDH [Time Frame: Baseline and as mean of visit Day 126, 140, 154 and 168]
Change in fatigue score, using the FACIT-Fatigue questionnaire [Time Frame: Baseline and as mean of visits Day 126, 140, 154 and Day 168]
Percentage of participants who remain free from transfusions [Time Frame: Day 14 and Day 168]
Rate of breakthrough hemolysis (BTH) [Time Frame: Day 1 and Day 168]
Rates of Major Adverse Vascular Events (MAVEs incl. thrombosis) [Time Frame: Day 1 and Day 168]
Secondary ID(s)
2019-004665-40
CLNP023C12302
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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