Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders

Immune Thrombocytopenia (ITP) Clinical Trial

Official title:

An Open-label, Multi-center, Phase 2 Basket Study to Assess Efficacy, Safety and Pharmacokinetics of Iptacopan (LNP023) in Participants With Autoimmune Benign Hematological Disorders

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05086744
• Other study ID #: CLNP023L12201
• Secondary ID: 2021-002039-40
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 21, 2021
• Est. completion date: April 30, 2024

Study information

• Verified date: March 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the efficacy and safety of iptacopan in participants with autoimmune benign hematological disorders such as primary immune thrombocytopenia and primary cold agglutinin disease.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: April 30, 2024
• Est. primary completion date: September 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

All Cohorts:

• Written informed consent
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections is required and vaccination against Haemophilus influenzae infection is recommended prior to the start of treatment.
• Weight of at least 35 kg

Cohort 1 specific inclusion criteria:

• Participants with a diagnosis of persistent or chronic primary ITP
• Participants must have received at least 1 unique prior therapy administered with the intention to treat ITP
• Sustained thrombocytopenia

Cohort 2 specific inclusion criteria:

• Participants with a diagnosis of primary CAD
• Participants must have received at least 1 unique prior therapy administered with the intention to treat CAD
• Laboratory evidence of ongoing hemolysis
• Sustained anemia Exclusion Criteria:

All cohorts:

• Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
• Past or concomitant use of medications prohibited by the protocol
• Known or suspected hereditary or acquired complement deficiency
• History of primary or secondary immunodeficiency, including a positive HIV test result
• Chronic infection with Hepatitis B or C virus
• History of recurrent invasive infections caused by encapsulated organisms, including Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae
• Presence or suspicion of any active infection within 14 days prior to first study drug administration.
• Any medical condition deemed likely to interfere with the participant's participation in the study
• Any malignant disease diagnosed within the past 5 years, with the exception of localized non-melanoma skin cancer, in situ cervical cancer, or, for CAD, a low-grade lymphoproliferative disorder.
• History of bone marrow/hematopoietic stem cell or solid organ transplantation.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of investigational drug and for 1 week after last iptacopan dose
• Active severe bleeding or history of intracranial hemorrhage.
• Liver disease, or liver injury as indicated by abnormal liver function tests.
• Severe concurrent comorbidities of unstable medical conditions.

Cohort 1 specific exclusion criteria:

• Secondary ITP, as may arise in the setting of certain autoimmune disorders, immunodeficiency syndromes, infections, malignancies, and drug treatments
• No ITP-directed background therapy permitted, with the exception of either a thrombopoietin receptor agonist or low-dose corticosteroid, as long as stable dosage for at least 4 weeks prior to first iptacopan dose
• Abnormal coagulation screening labs

Cohort 2 specific exclusion criteria:

• Secondary cold agglutinin syndrome, as may arise in the setting of certain infections, autoimmune disorders, and malignancies (with the exception of a low-grade lymphoproliferative disorder)
• No CAD-directed background therapy permitted Additional protocol-defined inclusion / exclusion criteria may apply.

Related Conditions & MeSH terms

• Anemia, Hemolytic, Autoimmune
• Cold Agglutinin Disease (CAD)
• Hematologic Diseases
• Immune Thrombocytopenia (ITP)
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Iptacopan
Iptacopan 200 mg BID

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Essen
Italy	Novartis Investigative Site	Milano	MI
Korea, Republic of	Novartis Investigative Site	Seoul
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Murcia
United Kingdom	Novartis Investigative Site	London
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet count	Cohort 1: Ability of iptacopan to induce a clinically meaningful increase in platelet count in participants with primary ITP	Day 1 to Day 85
Primary	Hemoglobin levels	Cohort 2: Ability of iptacopan to induce a clinically meaningful increase in hemoglobin levels in participants with primary CAD	Day 1 to Day 85
Secondary	Platelet count	Time to first response	Day 1 to Day 85
Secondary	Hemoglobin levels	Time to first response	Day 1 to Day 85
Secondary	Platelet count	Duration of response	Day 1 to Day 85
Secondary	Hemoglobin levels	Duration of response	Day 1 to Day 85
Secondary	Platelet count	Magnitude of response	Day 1 to Day 85
Secondary	Hemoglobin levels	Magnitude of response	Day 1 to Day 85
Secondary	Number of patients who use rescue therapy	Need for rescue therapy	Day 1 to Day 85
Secondary	Lactate dehydrogenase (LDH)	Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers	Screening, Day 15, Day 29, Day 85, Day 113
Secondary	Total billirubin	Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers	Screening, Day 15, Day 29, Day 85, Day 113
Secondary	Reticulocytes count	Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers	Screening, Baseline, Day 1, Day 15, Day 29, Day 85, Day 99, Day 113
Secondary	Haptoglobin	Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers	Screening, Day 15, Day 29, Day 85, Day 113
Secondary	Pharmacokinetic parameter: Cmax	Pharmacokinetics (PK) of iptacopan	Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Secondary	Pharmcokinetic parameter: AUCtau	Pharmacokinetics (PK) of iptacopan	Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Secondary	Pharmcokinetic parameter: AUClast	Pharmacokinetics (PK) of iptacopan	Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Secondary	Pharmcokinetic parameter: Ctrough	Pharmacokinetics (PK) of iptacopan	Day 15, Day 29 and Day 57: 0 hours/predose
Secondary	Pharmcokinetic parameter: Tmax	Pharmacokinetics (PK) of iptacopan	Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Secondary	Number of adverse events and serious adverse events	Safety and tolerability of iptacopan in participants with autoimmune benign hematological disorders	Up to end of study (Day 757) in Part B