Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

NCT03896152 | Completed Phase 2 Results

• 1 other identifier: CLNP023X2204
• Study Type: interventional
• Target: 13
• Locations: 4 countries
• Sites: 5

Brief Summary

This was a Phase II randomized, open-label, multicenter, efficacy, safety, pharmacokinetic and pharmacodynamic study assessing four iptacopan doses in adult Paroxysmal nocturnal hemoglobinuria (PNH) patients with active hemolysis who were not on eculizumab or any other complement inhibitor less than 3 months prior to first iptacopan dose. Active hemolysis was defined by a lactate dehydrogenase (LDH) value ≥ 1.5 × ULN.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

Complement; alternative pathway; paroxysmal nocturnal hemoglobinuria; hemolysis; LNP023; PNH; LDH; hemoglobin; Iptacopan

Outcome Measures

Primary Outcomes (1)

• Summary of Lactate Dehydrogenase (LDH) Responders

  A responder was defined as a patient with at least 60% reduction in LDH compared to Baseline or LDH below the upper limit of normal at any time up to and including Week 12 for that patient.

  Week 2, week 4, week 8 and week 12

Secondary Outcomes (21)

• Percent Change From Baseline in LDH Levels

  Baseline, week 2, week 4, week 8 and week 12

• Change From Baseline in Hemoglobin

  Baseline, Week 2, week 4, week 8 and week 12

• Change From Baseline in Free Hemoglobin

  Baseline, Week 2, week 4, week 8 and week 12

• Change From Baseline in Carboxyhemoglobin

  Baseline, Week 2, week 4, week 8 and week 12

• Change From Baseline in Absolute Reticulocyte Count (ARC)

  Baseline, week 2, week 4, week 8 and week 12

Study Arms (2)

LNP023 25 mg bid/100 mg bid

EXPERIMENTAL

Four weeks of treatment with iptacopan 25 mg bid in Period 1 followed by treatment with 100 mg bid in Period 2 and Period 3.

Drug: LNP023

LNP023 50 mg bid/200 mg bid

EXPERIMENTAL

Four weeks of treatment with iptacopan 50 mg bid in Period 1 followed by treatment with 200 mg bid in Period 2 and Period 3.

Drug: LNP023

Interventions

LNP023 DRUG

approximately 2 year of Treatment with LNP023

Also known as: iptacopan

LNP023 25 mg bid/100 mg bid; LNP023 50 mg bid/200 mg bid

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Male and female patients at least 18 years old at baseline.
• Diagnosis of active PNH based on documented clone size of ≥10% by RBCs and/or granulocytes, measured by GPI-deficiency on flow cytometry (screening or medical history data acceptable).
• LDH values \> 1.5 x upper limit of the normal range (ULN) for at least 3 measurements over a maximum of 8 weeks prior to Day 1 (Screening, baseline or medical history data acceptable).
• Hemoglobin level \< 10.5 g/dL at Baseline.
• For Period 3 of the study, patients who as per judgment of Investigator benefit from LNP023 treatment based on reduced hemolytic parameters as compared to Screening and Baseline.
• Vaccinations against N. meningitidis, S. pneumoniae and H. influenzae is required at least 4 weeks prior to first dosing with LNP023 (existing vaccinations should provide effective titers at time of LNP023 treatment start). If LNP023 treatment has to start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment must be initiated.
• Able to communicate well with the investigator, to understand and comply with the requirements of the study. -

You may not qualify if:

• Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment, or within 5 elimination half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
• Patients treated with eculizumab or any other complement inhibitor less than 3 months prior to study Day 1
• Known or suspected hereditary or acquired complement deficiency.
• History of currently active primary or secondary immunodeficiency.
• History of splenectomy.
• History of bone marrow/ hematopoietic stem cell or solid organ transplants (e.g. heart, lung, kidney, liver).
• Evidence of malignant disease, or malignancies diagnosed within the previous 5 years.
• Patients with laboratory evidence of bone marrow failure (reticulocytes \< 60x10E9/L, or platelets \< 50x10E9/L or neutrophils \< 1x10E9/L) verified both at screening and baseline.
• History of recurrent meningitis, history of meningococcal infections despite vaccination, as verified at both screening and baseline.
• Presence or suspicion (based on judgment of the investigator) of active infection within 2 weeks prior to first dose of LNP023, or history of severe recurrent bacterial infections.
• A positive HIV, Hepatitis B (HBV) or Hepatitis C (HCV) test result at screening.
• Patients on immunosuppressive agents such, as but not limited to, cyclosporine, tacrolimus, mycophenolate or mycophenolic acid, cyclophosphamide, methotrexate or IV immunoglobulins, less than 8 weeks prior to first treatment with LNP023, unless on a stable regimen for at least 3 months prior to first LNP023 dose.
• Systemic corticosteroids unless on a stable dose for at least 4 weeks before randomization.
• Severe concurrent co-morbidities not amenable to active treatment; e.g., patients with severe kidney disease (CKD stage 4, dialysis), advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or unstable thrombotic event, as judged by the investigator, both at screening and baseline (unless baseline was skipped).
• Any medical condition deemed likely to interfere with the patient's participation in the study, or likely to cause serious adverse events during the study.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Novartis Investigative Site

Kota Kinabalu, Sabah, 88586, Malaysia

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Publications (1)

• Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022 Aug 9;6(15):4450-4460. doi: 10.1182/bloodadvances.2022006960.

  PMID: 35561315 RESULT

Related Links

• Patient Lay Trial Summary

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Hemolysis

Interventions

iptacopan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, open label study

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: March 29, 2019
• Study Start: April 5, 2019
• Primary Completion: April 7, 2020
• Study Completion: February 9, 2022
• Last Updated: June 18, 2024
• Results First Posted: December 18, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

SG (1); TW (1); MY (1); KR (2)