An open label, multicenter roll-over extension program (REP) to characterize the long-term safety and tolerability of iptacopan (LNP023) in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who have completed PNH Phase II and Phase III studies with iptacopan

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hemolytic disorder
characterized by complementmediated
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.
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
To ensure continuous treatment of PNH patients upon completion of the Phase 2
and Phase 3 studies with iptacopan and to collect long-term safety,
tolerability and efficacy data, patients will be offered the opportunity to
enroll in this open-label roll-over extension study and receive open-label
treatment of 200 mg iptacopan b.i.d.
In summary, this study will provide continued access to iptacopan for
participants from the PNH Phase 2 and 3 studies through 3 years post last
patient first visit (LPFV) of the roll-over-extension study or until iptacopan
becomes commercially available in the respective country, whichever is shorter.
It is noteworthy to mention that this roll-over extension study will run in
parallel to the Phase 2 (LNP023X2201 and LNP023X2204) and Phase 3 (LNP023C12301
and LNP023C12302) studies.

This study has been transitioned to CTIS with ID 2023-509843-28-00 check the CTIS register for the current data.

The purpose of this study is to evaluate the long-term safety, tolerability and
efficacy of iptacopan in patients with PNH and to provide access to patients
who have completed the treatment extension period (without tapering down) of
the Phase 2 trials or completed any Phase 3 trials and derived benefit from
iptacopan treatment.

This study is an open-label, single arm, multicenter, roll-over extension study
to characterize long-term safety, tolerability and efficacy of iptacopan and to
provide access to iptacopan to patients with PNH who have completed the
treatment extension period (without tapering down) of the Novartis-sponsored
Phase II studies or completed any Phase III study with iptacopan

iptacopan (LNP023)

Vaccinations: Number of vaccinations depends on the titer of the vacinations
from the APPLY study.
Physical examination: 3x in the first year, 2x in the following years, 1x at
the end of the study
Blood pressure + pulse: 5x in the first year, 2x per year in following years,
1x at the end of the study
Body height: 1x
Body weight: 5x first year, 2x per year in following years, 1x at the end of
the study
Body temperature: 5x in the first year, 2x in the following years, 1x at the
end of the study
Pregnancy: 5x first year, 2x per year in following years, 1x at the end of the
study
Blood withdrawal: 4x first year, 2x per year in following years, 1x at the end
of the study
Urine examination: 4x first year, 2x per year in following years, 1x at the end
of the study
Blood transfusion: if necessary
ECG: 2x per year, 1x at the end of the study
Questionnaires (FACIT + PGIS): 4x in the first year, 2x per year in following
years, 1x at the end of the study
Questionnaires (EORTC + EQ-D5-5L): 2x in first year, 1x in following years, 1x
at end of study