Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy

NCT04820530 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CLNP023C123012020-003172-41
• Study Type: interventional
• Target: 40
• Locations: 8 countries
• Sites: 12

Brief Summary

The purpose of this Phase 3 study was to determine whether iptacopan is efficacious and safe for the treatment of Paroxysmal nocturnal hemoglobinuria (PNH) patients who were naïve to complement inhibitor therapy.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

Paroxysmal nocturnal hemoglobinuria; Hemoglobin; Anemia; LNP023; Iptacopan

Outcome Measures

Primary Outcomes (1)

• Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions

  Sustained increase in hemoglobin levels (responder) is defined as an increase from baseline in hemoglobin levels of ≥ 2 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the primary analysis.

  Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168

Secondary Outcomes (8)

• Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions

  Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168

• Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions

  Between Day 14 and Day 168

• Change From Baseline in Hemoglobin Levels in the Core Treatment Period

  Baseline, Day 126 to 168

• Percent Change From Baseline in LDH

  Baseline, Day 126 to 168

• Adjusted Annualized Clinical BTH Rate in the Core Treatment Period

  Between Day 1 and Day 168

Other Outcomes (8)

• Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions

  Baseline, Day 336

• Marginal Proportion (Expressed as Percentage) of Patients Not Receiving and Not Requiring RBC Transfusions

  Between Day 14 and Day 336

• Change From Baseline in Hemoglobin Levels

  Baseline, Day 336

Study Arms (1)

LNP023

EXPERIMENTAL

Participants receive LNP023 at a dose of 200 mg orally b.i.d

Drug: Iptacopan (LNP023)

Interventions

Iptacopan (LNP023) DRUG

Taken orally b.i.d. Dosage supplied: 200mg Dosage form: Hard gelatin capsule Route of Administration: oral

Also known as: Iptacopan

LNP023

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with RBCs and WBCs clone size ≥ 10%
• Mean hemoglobin level \<10 g/dL
• LDH \> 1.5 x Upper Limit of Normal (ULN)
• Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment
• If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given

You may not qualify if:

• Prior treatment with a complement inhibitor, including anti-C5 antibody
• Known or suspected hereditary complement deficiency
• History of hematopoietic stem cell transplantation
• Patients with laboratory evidence of bone marrow failure (reticulocytes \<100x109/L; platelets \<30x109/L; neutrophils \<0.5x109/L).
• Active systemic bacterial, viral (incl. COVID-19)or fungal infection within 14 days prior to study drug administration.
• 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., dialysis), advanced cardiac disease (e.g., NYHA class IV heart failure), 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Tianjin, 300020, China

Location

Novartis Investigative Site

Tianjin, 300052, China

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Aachen, 52074, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Avellino, AV, 83100, Italy

Location

Novartis Investigative Site

Kota Kinabalu, Sabah, 88586, Malaysia

Location

Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Related Publications (3)

• DeCastro C, Sheinberg P, Han B, Vallow S, Bermann G, Dhalke M, Kumar R, Dickie G, Galipeau N, Lamoureux R, Rupinski K, Lowe C, Nieves A, de Fontbrune FS, de Latour RP. Patient-Reported Meaningful Change in Symptoms and Impacts of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Three Phase III Clinical Trials of Iptacopan. Patient. 2025 Nov;18(6):699-712. doi: 10.1007/s40271-025-00755-5. Epub 2025 Jul 22.

  PMID: 40694294 DERIVED

• Risitano AM, Kulasekararaj AG, Scheinberg P, Roth A, Han B, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Lee LWL, Yap ES, Frieri C, Marano L, de Fontbrune FS, Gandhi S, Trikha R, Alashkar F, Yang C, Liu H, Kelly RJ, Hochsmann B, Lawniczek T, Mahajan N, Solar-Yohay S, Kerloeguen C, Ferber P, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, de Latour RP. Oral iptacopan monotherapy in paroxysmal nocturnal haemoglobinuria: final 48-week results from the open-label, randomised, phase 3 APPLY-PNH trial in anti-C5-treated patients and the open-label, single-arm, phase 3 APPOINT-PNH trial in patients previously untreated with complement inhibitors. Lancet Haematol. 2025 Jun;12(6):e414-e430. doi: 10.1016/S2352-3026(25)00081-X.

  PMID: 40447351 DERIVED

• Peffault de Latour R, Roth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Wong Lee Lee L, Yap ES, Sicre de Fontbrune F, Marano L, Alashkar F, Gandhi S, Trikha R, Yang C, Liu H, Kelly RJ, Hochsmann B, Kerloeguen C, Banerjee P, Levitch R, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, Risitano AM. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2024 Mar 14;390(11):994-1008. doi: 10.1056/NEJMoa2308695.

  PMID: 38477987 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Anemia

Interventions

iptacopan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: March 29, 2021
• Study Start: July 19, 2021
• Primary Completion: November 2, 2022
• Study Completion: April 18, 2023
• Last Updated: October 9, 2024
• Results First Posted: November 15, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

SG (1); DE (2); MY (2); IT (1); KR (1); GB (1); FR (1); CN (3)