The aim of this study is to determine whether LNP023 is effective and safe for the treatment of PNH. LNP023 is compared to the Standard of Care (SOC) anti-C5 antibody treatment. The primary objectives are to:• Demonstrate superiority of LNP023…
ID
Source
Brief title
Condition
- Haemolyses and related conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Endpoint(s) for primary objective(s)
• Response defined as having an increase from baseline in Hb >= 2 g/dL assessed
between Day 126 and Day 168, in the absence of packed red blood cell
transfusions between Day 14 and Day 168
• Response defined as having Hb >= 12 g/dL between Day 126 and Day 168 in the
absence of packed-red blood cell transfusions between Day 14 and Day 168
Secondary outcome
Endpoint(s) for secondary objective(s)
• Absence of administration of packed-red blood cell transfusions between Day
14 and Day 168
• Change from baseline in hemoglobin (g/dL) as mean of visits between Day 126
and Day 168
• Change from baseline in FACIT-Fatigue scores as mean of visits between Day
126 and Day 168
• Change from baseline in reticulocyte count (109/L) as mean of visits between
Day 126 and Day 168
• Percent change from baseline in LDH levels (U/L) as mean of visits between
Day 126 and Day 168
• Occurrences of breakthrough hemolysis reported between Day 1 and Day 168
• Occurrences of MAVEs occurring between Day 1 and Day 168
Background summary
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hemolytic disorder
characterized by complement-mediated intravascular hemolysis, bone marrow
failure (BMF) and severe thrombophilia.The clinical presentation is driven by
uncontrolled complement activation on CD55 and CD59 deficient PNH type RBC.
Thromboembolism is the leading cause of morbidity and mortality in patients
with PNH and can occur at any site.
Eculizumab is approved anti-C5 antibody therapie for the treatment of PNH and
the current Standard of Care (SoC).
There is a heterogeneous hematological response with eculizumab and a
substantial proportion of patients does not achiev normal or near normal
hemoglobin levels. The heterogeneous response to eculizumab or other anti-C5
antibody treatment can, in part, be explained through its mechanism of action
inhibiting intravascular hemolyse. LNP023 has the potential to prevent both
intra- and extravascular hemolysis, and therefore, offer therapeutic benefits
over and above the current SoC.
In this study the SoC is compared to LNP023 treatment. The main goal is to
determine whether LNP023 is efficacious and safe for the treatment of PNH.
LNP023 has not yet been approved ("registered") by the Dutch government as a
drug. Doctors are not allowed to prescribe LNP023. Patient studies are
required for registration. To date, approximately 102 healthy subjects and 29
patients with PNH have been treated with LNP023 in studies
Study objective
The aim of this study is to determine whether LNP023 is effective and safe for
the treatment of PNH. LNP023 is compared to the Standard of Care (SOC) anti-C5
antibody treatment.
The primary objectives are to:
• Demonstrate superiority of LNP023 compared to anti-C5 antibody treatment in
the proportion of participants achieving a sustained increase in hemoglobin
levels from baseline of >= 2 g/dL in the absence of red blood cell transfusions.
• Demonstrate superiority of LNP023, compared to anti-C5 antibody treatment, in
the proportion of participants achieving sustained hemoglobin levels >= 12 g/dL
in the absence of red blood cell transfusions.
The main clinical question of interest is: What is the treatment effect of
LNP023 200mg bid versus anti-C5 treatment in PNH patients with residual
anaemia. The endpoints here are:
- an increase in the Hb level from baseline by more than 2 g/dL
- and final HB levels in excess of 12g/dL. These measuring points are both
assessed between day 126 and 168.
- the need for RBC transfusion on day 14 and day 168.
Study design
This study is a multi-center, randomized, open-label, active
comparator-controlled, parallel group study, which is comprised of a screening
period, a 24-week, active controlled, parallel group treatment period and a
24-week LNP023 treatment extension period.
Intervention
LNP023 200mg bid
Study burden and risks
- A screening period of up to 8 weeks (unless it is necessary to extend it for
vaccinations However, it should be ticked off as soon as possible to avoid
extending the screening period).
-A treatment period of 24 weeks and an extension period of 24 weeks.
Participants who have started anti-C5 therapy may switch to LNP023 during the
extension period. Patients who started with LNP023 may continue with LNP023
during the extension period.
The prolongation period is also 24 weeks and starts on the day after the end of
the week 24 visit.
Participants who do not agree with the extension period have their last study
visit around 24 weeks.
Based on 20 visits, the burden will be as follows:
Physical examinations, ECGs, Vital functions, blood tests, pregnancy tests,
questionnaires. Vaccination if applicable: before the study and depending on
previous vaccinations
Optional: pharmacogenetics 1
Side effects of research medication and inconvenient research procedures.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004665-40-NL |
| ClinicalTrials.gov | NCT04558918 |
| CCMO | NL74786.100.20 |