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

The main purpose of this study was 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.

This was an open-label, single-arm (within each cohort), multi-center, non-confirmatory basket study to assess the efficacy, safety and pharmacokinetics of iptacopan in participants with autoimmune benign hematological disorders. The study was set up as a basket study to allow inclusion of new cohorts (indications). The study included 2 cohorts: primary immune thrombocytopenia (ITP) and primary cold agglutinin disease (CAD). Participants in Cohort 1 (ITP) were stratified in two groups according to high/low complement activation (i.e., based on sC5b-9 level at screening). No additional cohorts were added during the study.

The study consisted of a screening period, a 12-week treatment period (Part A), a washout (for responders)/follow-up (for non-responders) period after Part A, and, for responders only, an additional treatment extension period for up to 24 months (Part B). Non-responders who had signs of clinical benefit according to the Investigator's assessment could also continue treatment with iptacopan in Part B. The washout period prior to the start of part B lasted up to 4 weeks.

Eligibility Criteria:
Inclusion Criteria:

All Cohorts:

* Written informed consent
* Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections was 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