Study of efficacy and safety of twice daily oral LNP023 in adult PNH patients with residual anemia despite anti-C5 antibody treatment

• Register: EUCTR
• Last refreshed on: 2 May 2022
• Main ID: EUCTR2019-004665-40-NL
• Date of registration: 09/11/2020
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: Study of efficacy and safety of twice daily oral LNP023 in adult PNH patients with residual anemia despite anti-C5 antibody treatment
• Scientific title: A randomized, multicenter, active-comparator controlled, open-label trial to evaluate efficacy and safety of oral, twice daily LNP023 in adult patients with PNH and residual anemia, despite treatment with an intravenous anti-C5 antibody
• Date of first enrolment: 20/11/2020
• Target sample size: 91
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004665-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Ravulizumab and Eculizumab Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Canada, Czech Republic, Czechia, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
- Male and female participants = 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with 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

Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 82
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion criteria:
- Participants on a stable eculizumab dose but with a dosing interval of 11 days or less or participants on stable ravulizumab dose but with a dosing interval of less than 8 weeks
- 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 (Including 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 m^2, 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 exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Paroxysmal Nocturnal Hemoglobinuria (PNH)
MedDRA version: 21.1 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Product Name: iptacopan
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: iptacopan
Current Sponsor code: LNP023
Other descriptive name:  LNP023 HYDROCHLORIDE SALT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: iptacopan
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: iptacopan
Current Sponsor code: LNP023
Other descriptive name:  LNP023 HYDROCHLORIDE SALT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Soliris 300mg/30ml
Product Name: Eculizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ECULIZUMAB
CAS Number: 219685-50-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Ultomiris 300mg/30ml
Product Name: Ravulizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RAVULIZUMAB
Other descriptive name: ravulizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: - Proportion of participants who remain free from transfusions
- Average change in hemoglobin
- Change in fatigue score, using the FACIT-Fatigue questionnaire
- Average change in reticulocyte counts
- Average percent change in LDH
- Rate of breakthrough hemolysis (BTH)
- Rates of Major Adverse Vascular Events (MAVEs incl. thrombosis

Primary end point(s): - Proportion of participants achieving a sustained increase in hemoglobin levels from baseline of = 2 g/dL in the absence of red blood cell transfusions
- Proportion of participants achieving sustained hemoglobin levels = 12 g/dL in the absence of red blood cell transfusions.

Timepoint(s) of evaluation of this end point: Day 126 and Day 168

Main Objective: - Proportion of participants achieving a sustained increase in hemoglobin levels of = 2 g/dL in the absence of red blood cell transfusions
- Proportion of participants achieving sustained hemoglobin levels = 12 g/dL in the absence of red blood cell transfusions.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Day 14 and Day 168
2. Baseline and as mean of visit Day 126, 140, 154 and 168.
3. Baseline and as mean of visit Day 126, 140, 154 and 168.
4. Baseline and as mean of visit Day 126, 140, 154 and 168.
5. Baseline and as mean of visit Day 126, 140, 154 and 168.
6. Day 1 and Day 168.
7. Day 1 and Day 168.

Secondary end point(s): 1. Proportion of participants who remain free from transfusions
2. Change from baseline in hemoglobin (g/dL) as mean of visits between Day 126 and D168
3. Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168
4. Change from baseline in reticulocyte counts as mean of visits between Day 126 and Day 168
5. Percent change from baseline in LDH levels (U/L) as mean of visits between Day 126 and Day 168
6. Rate of breakthrough hemolysis (BTH)
7. Rates of Major Adverse Vascular Events (MAVEs incl. thrombosis

Secondary ID(s)

2019-004665-40-FR

CLNP023C12302

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 20/11/2020
Contact: