Study to assess the pharmacokinetics, safety, and tolerability of iptacopan in pediatric PNH patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Oct 2025 → ongoing

Decision date (initial)

2025-06-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG ORG-100003908

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Efficacy

To evaluate the safety and tolerability of iptacopan during the 26-week treatment period. To characterize the PK of iptacopan.

Secondary objectives 5

1. To evaluate the proportion of patients who achieve an increase in hemoglobin levels from baseline of ≥ 1 g/dL and the proportion of participants who achieve an increase in hemoglobin levels from baseline of ≥ 2 g/dL at 26 weeks and at 52 weeks (in the absence of RBC transfusions from Day 14 until the end of the 26-week and 52-week treatment periods).
2. To evaluate the proportion of participants achieving hemoglobin normalization at 26 weeks and at 52 weeks (in the absence of RBC transfusions from Day 14 until the end of the 26-week and 52-week treatment periods).
3. To evaluate transfusion avoidance as the proportion of participants who remain free from transfusions and do not meet transfusion criteria from Day 14 until the end of the 26-week treatment period and until the end of the 52-week treatment period.
4. To evaluate mean changes from baseline in hemoglobin and LDH at 26 weeks and at 52 weeks (evaluation of naive patients and prior anti-C5 treated patients, separately).
5. To evaluate the safety and tolerability of iptacopan during the 52-week treatment period.

Conditions and MedDRA coding

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-411560-PIP20-24

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male and female participants 2 to < 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with red blood cells (RBCs) and with white blood cells granulocytes/monocytes clone size ≥ 10%. The minimum body weight for patients in Cohort 1 is 35 kg.
2. Participants being treated with anti-C5 therapy and who have been on a stable regimen (dose and interval) for at least 6 months prior to enrollment, may be screened and enrolled in the study and switched to iptacopan irrespective of their anemia and hemolysis status, at the discretion of the Principal Investigator.
3. Participants who are anti-C5 treatment naive: mean hemoglobin level < 10 g/dL confirmed by central laboratory assessment during screening.
4. Participants who are anti-C5 treatment naive: lactate dehydrogenase (LDH) > 1.5 × upper limit of normal (ULN) documented by at least 2 laboratory measurements 2 to 6 weeks apart during the screening period, one of which is to be done by the central lab.
5. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated.
6. Vaccination against Haemophilus influenzae is recommended, according to local guidelines, at least 2 weeks before iptacopan.

Exclusion criteria 6

1. History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes.
2. Known or suspected hereditary complement deficiency at screening.
3. History of hematopoietic stem cell transplantation (HSCT) or scheduled for HSCT within 52 weeks from enrollment into the study (Day 1).
4. Participants with laboratory evidence of bone marrow failure (reticulocytes < 100 × 10^9/L, platelets < 30 × 10^9/L, neutrophils < 0.5 × 10^9/L).
5. Active systemic bacterial, viral (including COVID-19), or fungal infection within 14 days prior to study drug administration.
6. Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety evaluations, including AEs, SAEs, laboratory parameters, vital signs, and cardiovascular parameters.
2. PK parameters Cmax, AUClast, AUCtau (and other PK parameters in plasma, as appropriate), and Ctrough concentrations.

Secondary endpoints 5

1. Change in hemoglobin (Hb) from baseline ≥ 1 g/dL at Week 26 (in the absence of red blood cell (RBC) transfusions from Day 14). Change in Hb from baseline ≥ 1 g/dL at Week 52 (in the absence of RBC transfusions from Day 14). Change in Hb from baseline ≥ 2 g/dL at Week 26 (in the absence of RBC transfusions from Day 14). Change in Hb from baseline ≥ 2 g/dL at Week 52 (in the absence of RBC transfusions from Day 14).
2. Normal Hb at Weeks 26 in the absence of RBC transfusions from Day 14. Normal Hb at Week 52 in the absence of RBC transfusions from Day 14.
3. Absence of packed-RBC transfusions and not meeting transfusion criteria from Day 14 at Week 26. Absence of packed-RBC transfusions and not meeting transfusion criteria from Day 14 at Week 52.
4. Change from baseline in Hb and LDH at Week 26. Change from baseline in Hb and LDH at Week 52.
5. Safety evaluations (including AEs, SAEs, lab parameters, vital signs, and cardiovascular parameters).

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

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 19

Locations

5 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 83 files

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

Application history

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