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Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN (APPARENT)

Primary Purpose

IC-MPGN

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
iptacopan
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IC-MPGN focused on measuring LNP023, IC-MPGN, iptacopan, UPCR, eGFR, proteinuria

Eligibility Criteria

12 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male and female participants age ≥ 12 and ≤ 60 years at screening. Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to enrollment in adults and within 3 years of enrollment in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only). Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of an ACEI or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization UPCR ≥ 1.0 g/g (≥ 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15 Estimated GFR (using the chronic kidney disease [CKD]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15. Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. Exclusion Criteria: Participants who have undergone cell or solid organ transplantation, including kidney transplantation. Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions: Deposition of antigen-antibody immune complexes as a result of any chronic infections, including Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV); Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis Renal deposition of immune complexes as a result of a systemic autoimmune disease: Systemic lupus erythematosus (SLE) Sjögren syndrome Rheumatoid arthritis Mixed connective tissue disease Deposition of monoclonal immunoglobulins because of a monoclonal gammopathy due to plasma cell or B cell disorders. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care. Fibrillary glomerulonephritis Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with kidney biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli on the most recent biopsy. Kidney biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%. Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or the presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration. A history of recurrent invasive infections caused by encapsulated organisms, e.g., Neisseria meningitidis and Streptococcus pneumoniae. The use of inhibitors of complement factors (e.g., Factor B, Factor D, complement 3 (C3) inhibitors, anti-Complement 5 (C5) antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit. The use of immunosuppressants (except MPAs), cyclophosphamide or systemic corticosteroids at a dose >7.5 mg/day (or equivalent for a similar corticosteroid medication) within 90 days of study drug administration. The use of MPAs is not permitted within 90 days prior to randomization in India, as per the local health authority requirement. Acute post-infectious glomerulonephritis at screening, based upon the opinion of the investigator.

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

iptacopan 200mg b.i.d

Placebo to iptacopan 200mg b.i.d.

Arm Description

iptacopan 200mg b.i.d

Placebo to iptacopan 200mg b.i.d.

Outcomes

Primary Outcome Measures

Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months.
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months.
Log-transformed ratio to baseline in UPCR at the 12-month visit (both study treatment arms)
To evaluate the effect of iptacopan on proteinuria at 12 months.
Log-transformed ratio to 6-month visit in UPCR at the 12-month visit in the placebo arm.
To evaluate the effect of iptacopan on proteinuria at 12 months.

Secondary Outcome Measures

Change from baseline in eGFR
To demonstrate the superiority of iptacopan vs. placebo in improving estimated glomerular filtration rate (eGFR).
Change in eGFR from the 6-month visit to the 12- month visit of the placebo arm
To evaluate the effect at 12 months of iptacopan in improving eGFR
Proportion of patients achieved a composite renal endpoint
To demonstrate the superiority of iptacopan vs. placebo in the proportion of participant who achieved a composite renal endpoint at 6 and 12 months (both study arms).
Proportion of patients achieving a composite renal endpoint from the 6-month visit to the 12-month visit of the placebo arm
To evaluate the effect at 12 months of iptacopan on a composite renal endpoint in placebo arm
Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.
To demonstrate the superiority of iptacopan compared to placebo in improvement of patient-reported fatigue at 6 months and 12 months (both study arms).
Change in the FACIT-Fatigue score from the 6-month visit to the 12-month visit at the placebo arm
To evaluate the effect at 12 months of iptacopan in improvement of participant-reported fatigue in placebo arm
Number of participants with abnormal vital signs, ECGs and safety laboratory measurements
To evaluate the safety and tolerability of iptacopan compared to placebo, number of participants with abnormal vital signs (msDBP/msSBP/heart rate), ECGs and safety laboratory measurements will be collected. msDBP: mean sitting diastolic blood pressure msSBP: mean sitting systolic blood pressure
Number of participants with study drug discontinuation due to an AE
To evaluate the safety and tolerability of iptacopan compared to placebo, number of participants with study drug discontinuation due to an AE (or any safety issue) will be collected
Number of participants with clinically significant changes in heart rate, blood pressure, echocardiography parameters and NT-proBPN in adolescent patients
To evaluate the effect of iptacopan compared to placebo, number of participants with clinically significant changes in heart rate, blood pressure (msDBP/ msSBP), echocardiography parameters and NT-proBPN in adolescent patients will be collected

Full Information

First Posted
February 23, 2023
Last Updated
October 24, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05755386
Brief Title
Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN
Acronym
APPARENT
Official Title
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Iptacopan (LNP023) in Idiopathic Immune Complex Mediated Membranoproliferative Glomerulonephritis (IC-MPGN)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2, 2023 (Actual)
Primary Completion Date
June 30, 2026 (Anticipated)
Study Completion Date
June 30, 2026 (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
Yes

5. Study Description

Brief Summary
This study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis.
Detailed Description
The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (both administered in combination with standard of care) in participants (adults and adolescents aged 12-17 years) with idiopathic IC-MPGN. The study aims to demonstrate a reduction in proteinuria and improvement in estimated glomerular filtration rate (eGFR) in participants treated with iptacopan compared to placebo. Change in patient-reported fatigue will also be evaluated. Alternative complement pathway (AP) dysregulation is believed to underlie the clinical manifestations and progression of IC-MPGN. Upon completion of study treatment, participants will have the option to discontinue iptacopan treatment and enter a 30 day safety follow-up or continue iptacopan treatment by transitioning to an open label extension study (CLNP023B12001B; NCT03955445) and continue iptacopan treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IC-MPGN
Keywords
LNP023, IC-MPGN, iptacopan, UPCR, eGFR, proteinuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
iptacopan 200mg b.i.d
Arm Type
Experimental
Arm Description
iptacopan 200mg b.i.d
Arm Title
Placebo to iptacopan 200mg b.i.d.
Arm Type
Placebo Comparator
Arm Description
Placebo to iptacopan 200mg b.i.d.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to iptacopan 200mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)
Intervention Type
Drug
Intervention Name(s)
iptacopan
Intervention Description
iptacopan 200 mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)
Primary Outcome Measure Information:
Title
Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months.
Description
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months.
Time Frame
6 months (double-blind)
Title
Log-transformed ratio to baseline in UPCR at the 12-month visit (both study treatment arms)
Description
To evaluate the effect of iptacopan on proteinuria at 12 months.
Time Frame
12 months
Title
Log-transformed ratio to 6-month visit in UPCR at the 12-month visit in the placebo arm.
Description
To evaluate the effect of iptacopan on proteinuria at 12 months.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change from baseline in eGFR
Description
To demonstrate the superiority of iptacopan vs. placebo in improving estimated glomerular filtration rate (eGFR).
Time Frame
6 months of double-blind & 6 months of open label (up to 12 months)
Title
Change in eGFR from the 6-month visit to the 12- month visit of the placebo arm
Description
To evaluate the effect at 12 months of iptacopan in improving eGFR
Time Frame
month 6 and month 12
Title
Proportion of patients achieved a composite renal endpoint
Description
To demonstrate the superiority of iptacopan vs. placebo in the proportion of participant who achieved a composite renal endpoint at 6 and 12 months (both study arms).
Time Frame
6 months of double-blind & 6 months of open label (up to 12 months)
Title
Proportion of patients achieving a composite renal endpoint from the 6-month visit to the 12-month visit of the placebo arm
Description
To evaluate the effect at 12 months of iptacopan on a composite renal endpoint in placebo arm
Time Frame
month 6, month 12
Title
Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.
Description
To demonstrate the superiority of iptacopan compared to placebo in improvement of patient-reported fatigue at 6 months and 12 months (both study arms).
Time Frame
6 months of double-blind & 6 months of open label (up to 12 months)
Title
Change in the FACIT-Fatigue score from the 6-month visit to the 12-month visit at the placebo arm
Description
To evaluate the effect at 12 months of iptacopan in improvement of participant-reported fatigue in placebo arm
Time Frame
month 6, month 12
Title
Number of participants with abnormal vital signs, ECGs and safety laboratory measurements
Description
To evaluate the safety and tolerability of iptacopan compared to placebo, number of participants with abnormal vital signs (msDBP/msSBP/heart rate), ECGs and safety laboratory measurements will be collected. msDBP: mean sitting diastolic blood pressure msSBP: mean sitting systolic blood pressure
Time Frame
6 months of double-blind & 6 months of open label (up to 12 months)
Title
Number of participants with study drug discontinuation due to an AE
Description
To evaluate the safety and tolerability of iptacopan compared to placebo, number of participants with study drug discontinuation due to an AE (or any safety issue) will be collected
Time Frame
6 months of double-blind & 6 months of open label (up to 12 months)
Title
Number of participants with clinically significant changes in heart rate, blood pressure, echocardiography parameters and NT-proBPN in adolescent patients
Description
To evaluate the effect of iptacopan compared to placebo, number of participants with clinically significant changes in heart rate, blood pressure (msDBP/ msSBP), echocardiography parameters and NT-proBPN in adolescent patients will be collected
Time Frame
6 months of double-blind & 6 months of open label (up to 12 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female participants age ≥ 12 and ≤ 60 years at screening. Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to enrollment in adults and within 3 years of enrollment in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only). Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of an ACEI or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization UPCR ≥ 1.0 g/g (≥ 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15 Estimated GFR (using the chronic kidney disease [CKD]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15. Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. If not previously vaccinated, or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. Exclusion Criteria: Participants who have undergone cell or solid organ transplantation, including kidney transplantation. Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions: Deposition of antigen-antibody immune complexes as a result of any chronic infections, including Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV); Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis Renal deposition of immune complexes as a result of a systemic autoimmune disease: Systemic lupus erythematosus (SLE) Sjögren syndrome Rheumatoid arthritis Mixed connective tissue disease Deposition of monoclonal immunoglobulins because of a monoclonal gammopathy due to plasma cell or B cell disorders. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care. Fibrillary glomerulonephritis Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with kidney biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli on the most recent biopsy. Kidney biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%. Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or the presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration. A history of recurrent invasive infections caused by encapsulated organisms, e.g., Neisseria meningitidis and Streptococcus pneumoniae. The use of inhibitors of complement factors (e.g., Factor B, Factor D, complement 3 (C3) inhibitors, anti-Complement 5 (C5) antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit. The use of immunosuppressants (except MPAs), cyclophosphamide or systemic corticosteroids at a dose >7.5 mg/day (or equivalent for a similar corticosteroid medication) within 90 days of study drug administration. The use of MPAs is not permitted within 90 days prior to randomization in India, as per the local health authority requirement. Acute post-infectious glomerulonephritis at screening, based upon the opinion of the investigator.
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
Facility Information:
Facility Name
Novartis Investigative Site
City
Hachioji-city
State/Province
Tokyo
ZIP/Postal Code
193-0944
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Salamanca
State/Province
Castilla Y Leon
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Individual Site Status
Recruiting

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

Learn more about this trial

Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN

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