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Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS

Primary Purpose

Atypical Hemolytic Uremic Syndrome

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Iptcaopan 200 mg
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atypical Hemolytic Uremic Syndrome focused on measuring aHUS, iptacopan, atypical hemolytic uremic syndrome, thrombotic microangiopathy, TMA, dialysis, CKD, eGFR, PE/PI, Complement 3 Glomerulopathy (C3G), IgAN, PNH

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the open label extension study Willing and able to comply with the study Schedule of Activities Participants who have completed the full study treatment period of any prior "Novartis sponsored" iptacopan Phase 3 clinical trial in aHUS, are still on iptacopan study treatment and derive benefit from it as per Investigator's judgement Prior vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e., any boosters required should be administered according to local guidelines) Exclusion Criteria: Concomitant treatment with any complement inhibitor as well as concomitant treatment with any of the prohibited drugs Any comorbidity or medical condition (including but not limited to any active systemic bacterial, viral or fungal infection or malignancy) that, in the opinion of the Investigator could put the participant at risk Active infection or history of recurrent invasive infections caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae History of hypersensitivity to iptacopan or its excipients or to drugs of similar chemical classes Pregnant or nursing (lactating) women 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 stopping of investigational drug. Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Iptacopan 200 mg

    Arm Description

    Open label , single arm

    Outcomes

    Primary Outcome Measures

    Number of participants with adverse events and serious adverse events
    Number of participants with adverse events and serious adverse events will be provided
    Number of participants with abnormal safety laboratory parameters, vital signs and ECGs
    Number of participants with abnormal safety laboratory parameters , vital signs and ECGs will be provided

    Secondary Outcome Measures

    Number of participants with absence of aHUS relapse without the use of anti-C5 antibody
    Atypical hemolytic uremic syndrome (aHUS) relapse is defined by the coexistence of at least two of the following at the same visit: thrombocytopenia (platelet count < 150 x 109 /L), microangiopathic hemolytic anemia (hemoglobin < 10 g/dl, LDH > upper limit of normal, undetectable haptoglobin, presence of schistocyte on blood smear), worsening kidney function (serum creatinine or urine protein to creatinine ratio (UPCR) > upper limit of normal and an increase of ≥ 15% compared to baseline levels)
    Number of participants with complete TMA response status without the use of anti-C5 antibody therapy
    Complete thrombotic microangiopathy (TMA) Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 109/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline or ≥ 25% serum creatinine reduction compared to serum creatinine values prior to initiation of anti-C5 antibody therapy)
    Estimated glomerular filtration rate (eGFR)
    Estimated glomerular filtration rate (eGFR) based on eGFR categories will be collected. Serum creatinine as measured in mg/dL as part of the clinical chemistry panel through the central laboratory will be used to calculate the eGFR applying the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
    Chronic kidney disease (CKD) stage
    Chronic kidney disease (CKD) stage (1-5) based on eGFR categories will be provided: Stage 1 (G1): Kidney damage with normal kidney function Stage 2 (G2): Mild loss of kidney function Stage 3 (G3): 3a: Mild to moderate loss of kidney function; 3b: Moderate to severe loss of kidney function Stage 4 (G4): Severe loss of kidney function Stage 5 End stage renal disease (kidney failure): Kidney failure and need for transplant or dialysis
    Number of participants by dialysis requirement status
    Dialysis requirement status will be provided
    Number of participants with Thrombotic Microangiopathy (TMA) related adverse events
    TMA related events during the study defined as any of the following: Irreversible (>3 months) reduction in eGFR rate by ≥20%, not attributable to another cause An episode of acute kidney injury (AKI) attributed to a TMA that requires renal replacement therapy A non-renal manifestation of a TMA that requires hospitalization, or causes irreversible organ damage or death.

    Full Information

    First Posted
    March 21, 2023
    Last Updated
    July 10, 2023
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05795140
    Brief Title
    Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS
    Official Title
    A Multi-center, Single Arm, Open-label Extension Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Iptacopan in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Who Have Completed a Preceding Iptacopan Phase 3 Study in aHUS
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    February 12, 2024 (Anticipated)
    Primary Completion Date
    August 16, 2029 (Anticipated)
    Study Completion Date
    August 23, 2029 (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
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a multicenter, single arm, open-label, extension study to evaluate the long-term safety, tolerability, and efficacy of iptacopan in participants with aHUS.
    Detailed Description
    The extension study Baseline/Day 1 visit is equivalent to the End of Treatment visit of the parent study. The study will begin on Day 1 followed by on-site visits every 4 months during the study treatment period. A Safety Follow Up tele-visit must be conducted 7 days after last study treatment to collect information on Adverse Events.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Atypical Hemolytic Uremic Syndrome
    Keywords
    aHUS, iptacopan, atypical hemolytic uremic syndrome, thrombotic microangiopathy, TMA, dialysis, CKD, eGFR, PE/PI, Complement 3 Glomerulopathy (C3G), IgAN, PNH

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    150 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Iptacopan 200 mg
    Arm Type
    Experimental
    Arm Description
    Open label , single arm
    Intervention Type
    Drug
    Intervention Name(s)
    Iptcaopan 200 mg
    Other Intervention Name(s)
    LNP023
    Intervention Description
    Open label, participant specific kits, hard gelatin capsules to be taken twice a day
    Primary Outcome Measure Information:
    Title
    Number of participants with adverse events and serious adverse events
    Description
    Number of participants with adverse events and serious adverse events will be provided
    Time Frame
    Throughout the study duration, up to 4 years
    Title
    Number of participants with abnormal safety laboratory parameters, vital signs and ECGs
    Description
    Number of participants with abnormal safety laboratory parameters , vital signs and ECGs will be provided
    Time Frame
    Throughout the study duration, up to 4 years
    Secondary Outcome Measure Information:
    Title
    Number of participants with absence of aHUS relapse without the use of anti-C5 antibody
    Description
    Atypical hemolytic uremic syndrome (aHUS) relapse is defined by the coexistence of at least two of the following at the same visit: thrombocytopenia (platelet count < 150 x 109 /L), microangiopathic hemolytic anemia (hemoglobin < 10 g/dl, LDH > upper limit of normal, undetectable haptoglobin, presence of schistocyte on blood smear), worsening kidney function (serum creatinine or urine protein to creatinine ratio (UPCR) > upper limit of normal and an increase of ≥ 15% compared to baseline levels)
    Time Frame
    Throughout the study duration, up to 4 years
    Title
    Number of participants with complete TMA response status without the use of anti-C5 antibody therapy
    Description
    Complete thrombotic microangiopathy (TMA) Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 109/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline or ≥ 25% serum creatinine reduction compared to serum creatinine values prior to initiation of anti-C5 antibody therapy)
    Time Frame
    Throughout the study duration, up to 4 years
    Title
    Estimated glomerular filtration rate (eGFR)
    Description
    Estimated glomerular filtration rate (eGFR) based on eGFR categories will be collected. Serum creatinine as measured in mg/dL as part of the clinical chemistry panel through the central laboratory will be used to calculate the eGFR applying the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
    Time Frame
    Throughout study duration, up to 4 years
    Title
    Chronic kidney disease (CKD) stage
    Description
    Chronic kidney disease (CKD) stage (1-5) based on eGFR categories will be provided: Stage 1 (G1): Kidney damage with normal kidney function Stage 2 (G2): Mild loss of kidney function Stage 3 (G3): 3a: Mild to moderate loss of kidney function; 3b: Moderate to severe loss of kidney function Stage 4 (G4): Severe loss of kidney function Stage 5 End stage renal disease (kidney failure): Kidney failure and need for transplant or dialysis
    Time Frame
    Throughout study duration, up to 4 years
    Title
    Number of participants by dialysis requirement status
    Description
    Dialysis requirement status will be provided
    Time Frame
    Throughout the study duration, up to 4 years
    Title
    Number of participants with Thrombotic Microangiopathy (TMA) related adverse events
    Description
    TMA related events during the study defined as any of the following: Irreversible (>3 months) reduction in eGFR rate by ≥20%, not attributable to another cause An episode of acute kidney injury (AKI) attributed to a TMA that requires renal replacement therapy A non-renal manifestation of a TMA that requires hospitalization, or causes irreversible organ damage or death.
    Time Frame
    Throughout study duration, up to 4 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Signed informed consent must be obtained prior to participation in the open label extension study Willing and able to comply with the study Schedule of Activities Participants who have completed the full study treatment period of any prior "Novartis sponsored" iptacopan Phase 3 clinical trial in aHUS, are still on iptacopan study treatment and derive benefit from it as per Investigator's judgement Prior vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e., any boosters required should be administered according to local guidelines) Exclusion Criteria: Concomitant treatment with any complement inhibitor as well as concomitant treatment with any of the prohibited drugs Any comorbidity or medical condition (including but not limited to any active systemic bacterial, viral or fungal infection or malignancy) that, in the opinion of the Investigator could put the participant at risk Active infection or history of recurrent invasive infections caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae History of hypersensitivity to iptacopan or its excipients or to drugs of similar chemical classes Pregnant or nursing (lactating) women 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 stopping of investigational drug. Other protocol-defined inclusion/exclusion criteria may apply.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    +1-888-669-6682
    Email
    novartis.email@novartis.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    +41613241111
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Novartis Pharmaceuticals
    Organizational Affiliation
    Novartis Pharmaceuticals
    Official's Role
    Study Director

    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 eligible 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

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    Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS

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