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

Phase 3

Completed

• Conditions: hemolysis red blood cells; PNH; 10018911

• Registration Number: NL-OMON51938
• Lead Sponsor: ovartis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 2

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
granulocyte/monocyte 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
<100x109/L; platelets <30x109/L; neutrophils <500x106/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.

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Endpoint(s) for primary objective(s)<br /><br>• Response defined as having an increase from baseline in Hb >= 2 g/dL assessed<br /><br>between Day 126 and Day 168, in the absence of packed red blood cell<br /><br>transfusions between Day 14 and Day 168<br /><br>• Response defined as having Hb >= 12 g/dL between Day 126 and Day 168 in the<br /><br>absence of packed-red blood cell transfusions between Day 14 and Day 168</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Endpoint(s) for secondary objective(s)<br /><br>• Absence of administration of packed-red blood cell transfusions between Day<br /><br>14 and Day 168<br /><br>• Change from baseline in hemoglobin (g/dL) as mean of visits between Day 126<br /><br>and Day 168<br /><br>• Change from baseline in FACIT-Fatigue scores as mean of visits between Day<br /><br>126 and Day 168<br /><br>• Change from baseline in reticulocyte count (109/L) as mean of visits between<br /><br>Day 126 and Day 168<br /><br>• Percent change from baseline in LDH levels (U/L) as mean of visits between<br /><br>Day 126 and Day 168<br /><br>• Occurrences of breakthrough hemolysis reported between Day 1 and Day 168<br /><br>• Occurrences of MAVEs occurring between Day 1 and Day 168</p><br>