Long-term safety and tolerability of iptacopan in patients with Paroxysmal Nocturnal Hemoglobinuria

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Nov 2021 → ongoing

Decision date (initial)

2024-06-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-509843-28-00

EudraCT number

2020-004385-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the long-term safety and tolerability of iptacopan monotherapy in participants who have completed the treatment extension period (without tapering down) of the previous Phase II and any Phase III clinical studies with iptacopan

Secondary objectives 3

1. To evaluate the clinical benefit of iptacopan in maintaining sustained hemoglobin levels ≥ 12 g/dL, in the absence of red blood cell transfusion
2. To evaluate the clinical benefit of iptacopan in maintaining transfusion avoidance (TA) defined as the proportion of participants who remain free from transfusions
3. To evaluate the clinical benefit of iptacopan by assessing the rates of breakthrough hemolysis (BTH) and of Major Adverse Vascular Events (MAVE)

Conditions and MedDRA coding

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Male and female participants ≥ 18 years of age with a diagnosis of PNH who have completed the treatment extension period (without tapering down) of Phase II iptacopan studies (CLNP023X2204, CLNP023X2201), Period 4 of CLFGX2201 or completed any Phase III (eg. CLNP023C12302, CLNP023C12301, CLNP023C12303) clinical study at the time point of enrollment visit in this roll over extension study
2. Prior vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e., any boosters required administered according to local regulations).
3. Per investigator’s clinical judgement, the patient may benefit from continued treatment with iptacopan and has been clinically stable on iptacopan monotherapy for at least 3 months

Exclusion criteria 4

1. Any comorbidity or medical condition (including but not limited to any active systemic bacterial, viral or fungal infection or malignancy) that, in the opinion of the investigator, could put the subject at increased risk or potentially confound study data
2. History of recurrent invasive infections caused by encapsulated organisms, such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae
3. Female participants who are pregnant or breastfeeding, or intending to conceive during the course of the study
4. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using effective methods of contraception during dosing of investigational drug and for 1 week after stopping investigational drug. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety evaluations including but not limited to adverse events/serious adverse events, safety laboratory parameters, vital signs, etc., through End of Study visit

Secondary endpoints 4

1. Response defined as maintaining sustained hemoglobin levels ≥ 12 g/dL in the absence of transfusions evaluated over yearly follow up intervals
2. Absence of administration of packed-red blood cell transfusions evaluated over yearly follow up intervals
3. Occurrences of breakthrough hemolysis and of Major Adverse Vascular Events
4. MAVE occurring evaluated over yearly follow up intervals

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 11

Locations

7 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 73 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications