A multicenter, single arm, open-label trial to evaluate efficacy and safety of oral, twice daily iptacopan in adult PNH patients who have Hb≥10 g/dL in response to anti-C5 antibody and switch to iptacopan

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 Oct 2023 → 18 Oct 2024

Decision date (initial)

2023-09-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Therapy, Pharmacodynamic, Efficacy

The main question this trial is designed to answer: is iptacopan treatment equally effective to standard of care when switching treatment to iptacopan?

Secondary objectives 1

1. Is iptacopan better in effectiveness than standard of care treatment

Conditions and MedDRA coding

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed informed consent must be obtained prior to participation in the study
2. Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by PNH clone size WBCs ≥ 10% based on historical data.
3. Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or i.v. ravulizumab) for at least 6 months prior to screening
4. Mean hemoglobin level ≥10 g/dL, documented by the mean of all available Hb assessments (minimum 2 measurements) over a period of 6 months before screening visit, collected at any laboratory. In addition to fulfill the Hb eligibility criterion, participants must have two different samples collected during the screening period and tested by the central laboratory with the mean >10 g/dL, prior to starting iptacopan.
5. Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine are to be given according to local regulations, at least 2 weeks prior to first dosing. However, administration of these vaccines less than 2 weeks prior to start of iptacopan treatment is at the discretion of the investigator. If iptacopan treatment is started less than 2 weeks post-vaccination, participant must be given prophylactic antibiotic at the start of iptacopan and for at least 2 weeks after vaccination.
6. If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations. The vaccines should be given at least 2 weeks prior to initiation of iptacopan treatment. However, administration of these vaccines less than 2 weeks prior to start of iptacopan treatment, is at the discretion of the investigator. If iptacopan treatment is started less than 2 weeks post-vaccination, participant must be given prophylactic antibiotic at the start of iptacopan and for at least 2 weeks after vaccination.
7. Able to communicate well with the investigator, to understand and comply with the requirements of the study

Exclusion criteria 12

1. Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment
2. Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening
3. History of stem cell transplantation or any solid organ transplantation
4. Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration
5. Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration
6. Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening)
7. A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
8. Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening.
9. History of cancer of any part of the body within the past 5 years
10. Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial.
11. Any medical condition deemed likely to interfere with the patient's participation in the study
12. Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Measuring change in hemoglobin levels before start of iptacopan treatment and mean of hemoglobin levels at Day 126 and Day 168

Secondary endpoints 1

1. Measuring change in hemoglobin levels before start of iptacopan treatment and mean of hemoglobin levels at Day 126 and Day 168

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

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 21

Locations

4 EU/EEA countries · 17 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 11 files

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

Application history

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