E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune thrombocytopenia (ITP) Cold agglutinin disease (CAD) |
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E.1.1.1 | Medical condition in easily understood language |
Immune thrombocytopenia (ITP) Cold agglutinin disease (CAD) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10083842 |
E.1.2 | Term | Immune thrombocytopenia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068863 |
E.1.2 | Term | Cold agglutinin disease |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Cohort 1: To assess the ability of iptacopan to induce a clinically meaningful increase in platelet count in participants with primary ITP
Cohort 2: To assess the ability of iptacopan to induce a clinically meaningful increase in hemoglobin levels in participants with primary CAD
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E.2.2 | Secondary objectives of the trial |
• To assess the time to first response • To assess the duration of response during Part A • To assess the magnitude of response during Part A • To assess the need for rescue therapy during Part A • Cohort 2: To assess the effect of iptacopan on relevant disease biomarkers (BM) not covered in the primary objective during Part A • To assess the safety and tolerability of iptacopan in participants with benign hematological disorders • To assess the pharmacokinetics of iptacopan in the respective target populations
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 35kg
Cohort 1 specific inclusion criteria: •Male and female participants aged ≥18 years at baseline with a diagnosis of persistent or chronic primary ITP (diagnosed at least 3 months prior to baseline). • Participants must have received at least 1 unique prior therapy administered with the intention to treat ITP. • Sustained thrombocytopenia
Cohort 2 specific inclusion criteria: • Male and female participants aged ≥18 years at baseline with a diagnosis of primary CAD, including CAD arising in the setting of a low-grade lymphoproliferative disorder a) not requiring any therapy and b) without evidence of significant splenomegaly, hepatomegaly, or diffuse lymphadenopathy. • Positive direct antiglobulin test for C3d only (or predominantly) and cold agglutinin titer of ≥64 at 4°C. • Laboratory evidence of ongoing hemolysis. • Sustained anemia • Participants must have received at least 1 unique prior therapy administered with the intention to treat CAD |
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E.4 | Principal 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 co-morbidities 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 (TPO-RA) 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Cohort 1 (ITP): A clinically meaningful response, defined by a platelet count of ≥50 k/µL sustained for at least 2 consecutive weeks during the main, 12-week treatment part without the use of rescue therapy • Cohort 2 (CAD): A clinically meaningful response, defined by a hemoglobin level increase of ≥1.5 g/dL above baseline sustained for at least 2 consecutive weeks during the main, 12-week treatment part without the use of rescue therapy
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Cohort 1: Time to first platelet count ≥50 k/μL • Cohort 2: Time to first hemoglobin level ≥1.5 g/dL above baseline • Cohort 1: Duration during which platelet count remains ≥50k/μL without the use of rescue therapy • Cohort 2: Duration during which hemoglobin level remains ≥1.5 g/dL above baseline without the use of rescue therapy • Cohort 1: Magnitude of platelet count increase from baseline • Cohort 2: Magnitude of hemoglobin increase from baseline • Use of rescue therapy • Lactate dehydrogenase (LDH), total bilirubin, reticulocyte count and haptoglobin • Safety parameters include vital signs, adverse events, hematology, blood chemistry, reproductive and thyroid hormones, coagulation, urinalysis and ECG evaluation. • Iptacopan PK parameters including but not limited to Cmax, AUCtau, AUClast, Ctrough and Tmax. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Platelet count, Hemoglobin levels, Number of patients who use rescue therapy: Day 1 to Day 85
• Lactate dehydrogenase (LDH): Screening, Day 15, Day 29, Day 85, Day 113
• Total billirubin: Screening, Day 15, Day 29, Day 85, Day 113
• Reticulocytes count: Screening, Baseline, Day1, Day 15, Day 29, Day 85, Day 99, Day 113
• Haptoglobin: Screening, Day 15, Day 29, Day 85, Day 113
• Pharmacokinetic parameter: Day 15, Day 29, Day 57 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Korea, Republic of |
United Kingdom |
United States |
Germany |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |