Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders
Primary Purpose
Immune Thrombocytopenia (ITP), Cold Agglutinin Disease (CAD)
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Iptacopan
Sponsored by
About this trial
This is an interventional treatment trial for Immune Thrombocytopenia (ITP)
Eligibility Criteria
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.
Sites / Locations
- Massachusetts General Hospital
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Iptacopan 200 mg BID
Arm Description
Iptacopan 200 mg BID
Outcomes
Primary Outcome Measures
Platelet count
Cohort 1: Ability of iptacopan to induce a clinically meaningful increase in platelet count in participants with primary ITP
Hemoglobin levels
Cohort 2: Ability of iptacopan to induce a clinically meaningful increase in hemoglobin levels in participants with primary CAD
Secondary Outcome Measures
Platelet count
Time to first response
Hemoglobin levels
Time to first response
Platelet count
Duration of response
Hemoglobin levels
Duration of response
Platelet count
Magnitude of response
Hemoglobin levels
Magnitude of response
Number of patients who use rescue therapy
Need for rescue therapy
Lactate dehydrogenase (LDH)
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Total billirubin
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Reticulocytes count
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Haptoglobin
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Pharmacokinetic parameter: Cmax
Pharmacokinetics (PK) of iptacopan
Pharmcokinetic parameter: AUCtau
Pharmacokinetics (PK) of iptacopan
Pharmcokinetic parameter: AUClast
Pharmacokinetics (PK) of iptacopan
Pharmcokinetic parameter: Ctrough
Pharmacokinetics (PK) of iptacopan
Pharmcokinetic parameter: Tmax
Pharmacokinetics (PK) of iptacopan
Number of adverse events and serious adverse events
Safety and tolerability of iptacopan in participants with autoimmune benign hematological disorders
Full Information
NCT ID
NCT05086744
First Posted
September 28, 2021
Last Updated
September 27, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05086744
Brief Title
Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 21, 2021 (Actual)
Primary Completion Date
September 20, 2023 (Actual)
Study Completion Date
November 3, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Thrombocytopenia (ITP), Cold Agglutinin Disease (CAD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This is a basket study with different Cohorts.
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Iptacopan 200 mg BID
Arm Type
Experimental
Arm Description
Iptacopan 200 mg BID
Intervention Type
Drug
Intervention Name(s)
Iptacopan
Other Intervention Name(s)
Generic name: iptacopan, Investigational new drug, company code: LNP023
Intervention Description
Iptacopan 200 mg BID
Primary Outcome Measure Information:
Title
Platelet count
Description
Cohort 1: Ability of iptacopan to induce a clinically meaningful increase in platelet count in participants with primary ITP
Time Frame
Day 1 to Day 85
Title
Hemoglobin levels
Description
Cohort 2: Ability of iptacopan to induce a clinically meaningful increase in hemoglobin levels in participants with primary CAD
Time Frame
Day 1 to Day 85
Secondary Outcome Measure Information:
Title
Platelet count
Description
Time to first response
Time Frame
Day 1 to Day 85
Title
Hemoglobin levels
Description
Time to first response
Time Frame
Day 1 to Day 85
Title
Platelet count
Description
Duration of response
Time Frame
Day 1 to Day 85
Title
Hemoglobin levels
Description
Duration of response
Time Frame
Day 1 to Day 85
Title
Platelet count
Description
Magnitude of response
Time Frame
Day 1 to Day 85
Title
Hemoglobin levels
Description
Magnitude of response
Time Frame
Day 1 to Day 85
Title
Number of patients who use rescue therapy
Description
Need for rescue therapy
Time Frame
Day 1 to Day 85
Title
Lactate dehydrogenase (LDH)
Description
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Time Frame
Screening, Day 15, Day 29, Day 85, Day 113
Title
Total billirubin
Description
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Time Frame
Screening, Day 15, Day 29, Day 85, Day 113
Title
Reticulocytes count
Description
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Time Frame
Screening, Baseline, Day 1, Day 15, Day 29, Day 85, Day 99, Day 113
Title
Haptoglobin
Description
Cohort 2 (CAD) only: Effect of iptacopan on relevant disease biomarkers
Time Frame
Screening, Day 15, Day 29, Day 85, Day 113
Title
Pharmacokinetic parameter: Cmax
Description
Pharmacokinetics (PK) of iptacopan
Time Frame
Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Title
Pharmcokinetic parameter: AUCtau
Description
Pharmacokinetics (PK) of iptacopan
Time Frame
Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Title
Pharmcokinetic parameter: AUClast
Description
Pharmacokinetics (PK) of iptacopan
Time Frame
Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Title
Pharmcokinetic parameter: Ctrough
Description
Pharmacokinetics (PK) of iptacopan
Time Frame
Day 15, Day 29 and Day 57: 0 hours/predose
Title
Pharmcokinetic parameter: Tmax
Description
Pharmacokinetics (PK) of iptacopan
Time Frame
Day 15 and Day 57: 0 hours, 0.5 hours, 1 hour, 2 hours, 4 hours and 6 hours
Title
Number of adverse events and serious adverse events
Description
Safety and tolerability of iptacopan in participants with autoimmune benign hematological disorders
Time Frame
Up to end of study (Day 757) in Part B
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Novartis Investigative Site
City
Murcia
ZIP/Postal Code
30008
Country
Spain
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient level data and supporting clinical documents from applicable studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Learn more about this trial
Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders
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