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出境医 / 临床实验 / OL Extension Study of LNP023 in C3G

OL Extension Study of LNP023 in C3G

Study Description
Brief Summary:
This is an open-label extension study to evaluate the long-term efficacy, safety and tolerability of LNP023 in subjects with C3 glomerulopathy

Condition or disease Intervention/treatment Phase
C3 Glomerulopathy Drug: LNP023 Phase 2

Detailed Description:
The purpose of this extension study is to collect and evaluate long-term efficacy, safety and tolerability data in eligible participants receiving open label LNP023 after completing the C3G proof of concept (PoC) study CLNP023X2202. Efficacy assessments at the 9 month visit of the extension study in combination with data from CLNP023X2202 (baseline plus 3 months of treatment) will afford the opportunity to evaluate the effects of LNP023 on potential endpoint(s) for the Phase III trial in C3G at 12 months of treatment. Longer-term efficacy assessments may be used as supportive information for registration purposes.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Non-randomized Extension Study to Evaluate the Long-term Efficacy, Safety and Tolerability of LNP023 in Subjects With C3 Glomerulopathy
Actual Study Start Date : October 3, 2019
Estimated Primary Completion Date : October 31, 2024
Estimated Study Completion Date : December 2, 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: Open Label LNP023
LNP023 capsules formulation
 Drug: LNP023
LNP023 capsules
Outcome Measures
Primary Outcome Measures :
  1. Number of participants with composite renal response [ Time Frame: 9-months visit ]
    A participant is defined as a responder for the composite renal response endpoint if they meet the following criteria at the 9-month visit in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., ≥ the lower limit of normal (LLN)). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a non-responder.

  2. Number of participants with Adverse Events [ Time Frame: 90 days post LPLT ]
    Evaluate the long-term safety and tolerability of LNP023 in subjects with C3G by occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory parameters, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue).


Secondary Outcome Measures :
  1. Change in urine protein/creatinine ratio (UPCR) [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in UPCR at 9 months visit compared to CLNP023X2202 baseline

  2. Change in Urine albumin/creatinine ratio (UACR ) [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in UACR at 9 months visit compared to CLNP023X2202 baseline

  3. Change in serum creatinine [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in serum creatinine at 9 months visit compared to CLNP023X2202 baseline

  4. Change in estimated glomerular filtration rate(eGFR) [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in eGFR at 9 months visit compared to CLNP023X2202 baseline

  5. Status of C3G disease progression [ Time Frame: 6 to 9 months ]
    Describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at 6 to 9 months from entry to the study compared to those obtained prior to treatment in the CLNP023X2202 study

  6. Levels of complement component C3 [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component C3 at the 9 months visit

  7. Levels of complement component Bb [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component Bb at the 9 months visit

  8. Levels of complement component sC5b-9 [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component sC5b-9 at the 9 months visit

  9. Urine markers of renal damage [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on urine markers of renal damage by assessing the change from baseline in urinary kidney biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) at the 9 months visit in study compared to the CLNP023X2202 baseline visit

  10. Longer term effect on the composite renal response endpoint, renal function, renal histopathology and specific components of the complement pathway [ Time Frame: > 9 months ]
    Responder is defined if following criteria at times >9 and < 36 mon are met: (1) a stable or improved eGFR compared to baseline visit (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to baseline visit or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., LLN). Initiation of treatment with eculizumab or any other C-pathway modifying agent automatically designates the participant as a non-responder. Change from baseline in log-transformed UPCR, log transformed UACR, serum creatinine concentration and estimated glomerular filtration rate (eGFR) at times >9 and < 36 mon. Change in C3 deposit score, disease activity and chronicity scores from a renal biopsy at times >9 and < 36 mon from entry to the study. Change from baseline in circulating levels of C-pathway components C3, Bb and sC5b- 9 at times >9 and < 36 mon.

  11. Pharmacokinetics of LNP023 in subjects under prolonged treatment by determining plasma LNP023 concentration up to 12 months at trough [ Time Frame: 3-months, 6-months, 9-months and 12-months visits ]
    Measurement of LNP023 plasma concentration.

  12. Change from baseline in log-transformed urine protein/creatinine ratio (UPCR) [ Time Frame: 3 months ]
    To assess the effect of LNP023 on UPCR

  13. Change from baseline in log-transformed urine albumin/creatinine [ Time Frame: 3 months visit ]
    To assess the effect of LNP023 on urine albumin/creatinine


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Patients must have completed the treatment period of the CLNP023X2202 trial on study drug

Exclusion Criteria:

  • Severe concurrent co-morbidities, e.g. advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or any illness or medical condition that in the opinion of the investigator and sponsor is likely to prevent the patient from safely tolerating LNP023 or complying with the requirements of the study
  • Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to screening, or The presence of fever ≥ 38oC (100.4oF) within 7 days prior to screening.
  • History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects
  • History of HIV or any other immunodeficiency disease
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
Layout table for location information
United States, Iowa
Novartis Investigative Site Recruiting
Iowa City, Iowa, United States, 52242
France
Novartis Investigative Site Recruiting
Montpellier, France, 34295
Novartis Investigative Site Recruiting
Paris, France, 75015
Germany
Novartis Investigative Site Active, not recruiting
Essen, Germany, 45147
Italy
Novartis Investigative Site Recruiting
Ranica, BG, Italy, 24020
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28041
United Kingdom
Novartis Investigative Site Recruiting
London, United Kingdom, W12 0NN
Novartis Investigative Site Active, not recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Novartis Pharmaceuticals
Tracking Information
First Submitted Date  ICMJE May 3, 2019
First Posted Date  ICMJE May 20, 2019
Last Update Posted Date March 26, 2021
Actual Study Start Date  ICMJE October 3, 2019
Estimated Primary Completion Date October 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2020)
  • Number of participants with composite renal response [ Time Frame: 9-months visit ]
    A participant is defined as a responder for the composite renal response endpoint if they meet the following criteria at the 9-month visit in CLNP023B12001B: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., ≥ the lower limit of normal (LLN)). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a non-responder.
  • Number of participants with Adverse Events [ Time Frame: 90 days post LPLT ]
    Evaluate the long-term safety and tolerability of LNP023 in subjects with C3G by occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory parameters, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue).
Original Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Number of participants with composite renal response [ Time Frame: 9-months visit ]
    A subject is defined as a responder for the composite renal response endpoint if he/she meets the following criteria at the 9 months visit (1) a stable or improved eGFR and (2) a reduction in proteinuria and (3) an increase in C3 compared to the CLNP023X2202 baseline visit.
  • Number of participants with Adverse Events [ Time Frame: 90 days post LPLT ]
    Evaluate the long-term safety and tolerability of LNP023 in subjects with C3G by occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory parameters, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2020)
  • Change in urine protein/creatinine ratio (UPCR) [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in UPCR at 9 months visit compared to CLNP023X2202 baseline
  • Change in Urine albumin/creatinine ratio (UACR ) [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in UACR at 9 months visit compared to CLNP023X2202 baseline
  • Change in serum creatinine [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in serum creatinine at 9 months visit compared to CLNP023X2202 baseline
  • Change in estimated glomerular filtration rate(eGFR) [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in eGFR at 9 months visit compared to CLNP023X2202 baseline
  • Status of C3G disease progression [ Time Frame: 6 to 9 months ]
    Describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at 6 to 9 months from entry to the study compared to those obtained prior to treatment in the CLNP023X2202 study
  • Levels of complement component C3 [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component C3 at the 9 months visit
  • Levels of complement component Bb [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component Bb at the 9 months visit
  • Levels of complement component sC5b-9 [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component sC5b-9 at the 9 months visit
  • Urine markers of renal damage [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on urine markers of renal damage by assessing the change from baseline in urinary kidney biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) at the 9 months visit in study compared to the CLNP023X2202 baseline visit
  • Longer term effect on the composite renal response endpoint, renal function, renal histopathology and specific components of the complement pathway [ Time Frame: > 9 months ]
    Responder is defined if following criteria at times >9 and < 36 mon are met: (1) a stable or improved eGFR compared to baseline visit (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to baseline visit or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., LLN). Initiation of treatment with eculizumab or any other C-pathway modifying agent automatically designates the participant as a non-responder. Change from baseline in log-transformed UPCR, log transformed UACR, serum creatinine concentration and estimated glomerular filtration rate (eGFR) at times >9 and < 36 mon. Change in C3 deposit score, disease activity and chronicity scores from a renal biopsy at times >9 and < 36 mon from entry to the study. Change from baseline in circulating levels of C-pathway components C3, Bb and sC5b- 9 at times >9 and < 36 mon.
  • Pharmacokinetics of LNP023 in subjects under prolonged treatment by determining plasma LNP023 concentration up to 12 months at trough [ Time Frame: 3-months, 6-months, 9-months and 12-months visits ]
    Measurement of LNP023 plasma concentration.
  • Change from baseline in log-transformed urine protein/creatinine ratio (UPCR) [ Time Frame: 3 months ]
    To assess the effect of LNP023 on UPCR
  • Change from baseline in log-transformed urine albumin/creatinine [ Time Frame: 3 months visit ]
    To assess the effect of LNP023 on urine albumin/creatinine
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Change in UPCR [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in UPCR at 9 months visit compared to CLNP023X2202 baseline
  • Change in UACR [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in UACR at 9 months visit compared to CLNP023X2202 baseline
  • Change in serum creatinine [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in serum creatinine at 9 months visit compared to CLNP023X2202 baseline
  • Change in eGFR [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in eGFR at 9 months visit compared to CLNP023X2202 baseline
  • Status of C3G disease progression [ Time Frame: 6 to 9 months ]
    Describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at 6 to 9 months from entry to the study compared to those obtained prior to treatment in the CLNP023X2202 study
  • Levels of complement component C3 [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component C3 at the 9 months visit
  • Levels of complement component Bb [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component Bb at the 9 months visit
  • Levels of complement component sC5b-9 [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on specific component of the complement pathway by assessing the change from CLNP023X2202 baseline in circulating levels of complement component sC5b-9 at the 9 months visit
  • Urine markers of renal damage [ Time Frame: 9-months visit ]
    Long-term effect of LNP023 on urine markers of renal damage by assessing the change from baseline in urinary kidney biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) at the 9 months visit in study compared to the CLNP023X2202 baseline visit
  • Longer term effect on the composite renal response endpoint, renal function, renal histopathology and specific components of the complement pathway [ Time Frame: > 9 months ]
    Longer term (>9 months of treatment) effects of LNP023 on renal function and specific components of the complement pathway in C3G subjects by assessing change from CLNP023X2202 baseline in log-transformed UPCR, log-transformed UACR, serum creatinine concentration and estimated glomerular filtration rate (eGFR) at times >9 months. Change in C3 deposit score, disease activity and chronicity scores from a renal biopsy; and change from CLNP023X2202 baseline in circulating levels of complement pathway components C3, Bb and sC5b-9 at times >9 months.
  • LNP023 concentration [ Time Frame: 3-months, 6-months, 9-months and 12-months visits ]
    Pharmacokinetics of LNP023 in subjects under prolonged treatment by determining plasma LNP023 concentration up to 12 months at trough.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE OL Extension Study of LNP023 in C3G
Official Title  ICMJE An Open-label, Non-randomized Extension Study to Evaluate the Long-term Efficacy, Safety and Tolerability of LNP023 in Subjects With C3 Glomerulopathy
Brief Summary This is an open-label extension study to evaluate the long-term efficacy, safety and tolerability of LNP023 in subjects with C3 glomerulopathy
Detailed Description The purpose of this extension study is to collect and evaluate long-term efficacy, safety and tolerability data in eligible participants receiving open label LNP023 after completing the C3G proof of concept (PoC) study CLNP023X2202. Efficacy assessments at the 9 month visit of the extension study in combination with data from CLNP023X2202 (baseline plus 3 months of treatment) will afford the opportunity to evaluate the effects of LNP023 on potential endpoint(s) for the Phase III trial in C3G at 12 months of treatment. Longer-term efficacy assessments may be used as supportive information for registration purposes.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE C3 Glomerulopathy
Intervention  ICMJE Drug: LNP023
LNP023 capsules
Study Arms  ICMJE Experimental: Open Label LNP023
LNP023 capsules formulation
Intervention: Drug: LNP023
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 5, 2020) 		27
Original Estimated Enrollment  ICMJE
 (submitted: May 15, 2019) 		58
Estimated Study Completion Date  ICMJE December 2, 2024
Estimated Primary Completion Date October 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

- Patients must have completed the treatment period of the CLNP023X2202 trial on study drug

Exclusion Criteria:

  • Severe concurrent co-morbidities, e.g. advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or any illness or medical condition that in the opinion of the investigator and sponsor is likely to prevent the patient from safely tolerating LNP023 or complying with the requirements of the study
  • Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to screening, or The presence of fever ≥ 38oC (100.4oF) within 7 days prior to screening.
  • History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects
  • History of HIV or any other immunodeficiency disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE France,   Germany,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03955445
Other Study ID Numbers  ICMJE CLNP023B12001B
2018-004253-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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