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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Immune Thrombocytopenia (ITP), Cold Agglutinin Disease (CAD)

Intervention / Treatment
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* Drug: Iptacopan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a basket study with different Cohorts.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iptacopan 200 mg BID<br>Iptacopan 200 mg BID | Drug: Iptacopan<br>* Iptacopan 200 mg BID<br>* Other names: company code: LNP023;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet count | Time to first response | Day 1 to Day 85 | 
| Hemoglobin levels | Time to first response | Day 1 to Day 85 | 
| Platelet count | Duration of response | Day 1 to Day 85 | 
| Hemoglobin levels | Duration of response | Day 1 to Day 85 | 
| Platelet count | Magnitude of response | Day 1 to Day 85 | 
| Hemoglobin levels | Magnitude of response | Day 1 to Day 85 | 
| Number of patients who use rescue therapy | Need for rescue therapy | Day 1 to Day 85 | 
| Lactate dehydrogenase (LDH) | Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers | Screening, Day 15, Day 29, Day 85, Day 113 | 
| Total billirubin | Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers | Screening, Day 15, Day 29, Day 85, Day 113 | 
| 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 | 
| Haptoglobin | Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers | Screening, Day 15, Day 29, Day 85, Day 113 | 
| 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 | 
| 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 | 
| 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 | 
| Pharmcokinetic parameter: Ctrough | Pharmacokinetics (PK) of iptacopan | Day 15, Day 29 and Day 57: 0 hours/predose | 
| 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 | 
| 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 |