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Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy

Primary Purpose

Immunoglobulin A Nephropathy

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
SM101
Placebo
Sponsored by
Baxalta now part of Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Immunoglobulin A Nephropathy focused on measuring IgAN

Eligibility Criteria

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

Inclusion Criteria:

  1. 18 years of age or older at the time of screening
  2. Participant may be of any race or ethnicity
  3. Participant must have a biopsy-proven diagnosis of IgAN.
  4. Participant's blood pressure is ≤130/80 mmHg at Screening
  5. Participant is on maximally tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) for at least 3 months prior to the baseline visit.
  6. Participant must present at screening with current proteinuria levels between 1 g/24 h and 3.5 g/24 h, based on spot urine protein-to-creatinine ratio (UPCR)
  7. Participant must present at screening with an estimated glomerular filtration rate (eGFR) >40mL/min/1.73m^2
  8. If a female of childbearing potential, participant must have a negative pregnancy test at screening, is not currently breastfeeding, and agrees to employ adequate birth control measures for the duration of the study. Male participants with female partners of childbearing potential must agree to use adequate birth control measures for the duration of the study
  9. Participant is willing and able to comply with the requirements of this protocol and agrees to sign an informed consent form prior to any study-related activities

Exclusion Criteria:

  1. Participant has a history or current evidence of renal disease other than IgAN
  2. Participants with evidence of rapidly progressive disease
  3. Participant has IgAN with histologic evidence of advanced tubular atrophy and interstitial
  4. History or current evidence of other autoimmune disease
  5. History or current evidence of any chronic or uncontrolled medical condition which could, in the opinion of the Investigator, affect the participant's safety and ability to adhere to this protocol
  6. History or current evidence of a severe acute or chronic infection
  7. Use of systemic corticosteroids within 3 months prior to baseline, or anticipated use during the treatment period (Week 1 through Week 4). Note: Corticosteroids administered by inhalation or intranasally, or limited topical use of low-potency topical corticosteroids are allowed throughout the study.
  8. Known hypersensitivity or allergic reaction to any E. coli-derived recombinant product, yeast extract, or to the IP or any of its excipients
  9. Treatment with any immunomodulatory/immunosuppressive compound or monoclonal antibody for any indication within 6 months (unless otherwise stated) prior to screening (eg, B cell-depleting agents [eg, rituximab, epratuzumab] for ≥48 weeks; B-cell modifying agents [eg, belimumab, atacicept] for ≥24 weeks; IV immunoglobulins for ≥12 weeks and all other immunosuppressive treatments [eg, methotrexate, cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine] for ≥12 weeks)
  10. Clinically significant laboratory abnormalities prior to baseline
  11. History of any malignancy within past 5 years prior to screening (except for basal and squamous cell carcinomas of the skin, in situ cervical cancer, and stable prostate cancer that does not require treatment)
  12. History of tonsillectomy within 2 months prior to screening
  13. Participation in another clinical study involving an IP or investigational device within 30 days prior to screening or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
  14. Participant is a family member or employee of the Investigator
  15. A female participant who is pregnant or nursing at the time of screening

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    SM101 12 mg/kg

    SM101 24 mg/kg

    Placebo

    Arm Description

    Human soluble recombinant Fcγ Receptor IIB

    Human soluble recombinant Fcγ Receptor IIB

    L-histidine-buffered saline with mannitol, sucrose, and polysorbate 2

    Outcomes

    Primary Outcome Measures

    Percent change in proteinuria from Baseline to Week 24

    Secondary Outcome Measures

    Number of participants who demonstrate a ≥30% reduction from Baseline in proteinuria
    Number of participants who reach and maintain proteinuria levels below 1.0 g/24 h
    Mean change from Baseline in Estimated glomerular filtration rate (eGFR)
    Number of participants who experience any treatment-related serious adverse event (SAE) or severe adverse events (AE) during the course of the treatment period or subsequent follow-up period
    Number of participants who experience serious adverse events (SAEs) or adverse events (AEs)
    Number of participants who experience temporally-related adverse events (AEs)
    Temporally-related AEs - defined as AEs occurring during investigational product (IP) administration or within 72 hours of IP administration, regardless of causality
    Number of participants with any clinically significant change in vital signs during investigational product (IP) administration or within 30 minutes following administration
    Number of infusions associated with adverse events (AEs) or serious adverse events (SAEs) , regardless of causality
    Number of infusions that had to be slowed, interrupted, or terminated due to adverse events (AEs) or serious adverse events (SAEs)
    Number of participants with detectable levels of antidrug antibodies (ADAs)
    Clinically significant abnormal laboratory assessments
    Pharmacokinetics: maximum observed concentration (Cmax)
    Pharmacokinetics: time of maximum observed concentration (Cmax)
    Pharmacokinetics: area under the concentration-time curve during a dosing interval (AUC(0-tau))
    Pharmacokinetics: terminal half-life (t1/2)
    Pharmacokinetics: systemic clearance (CL)
    Pharmacokinetics: volume of distribution at the terminal phase (Vz)
    Pharmacokinetics: volume of distribution at steady state (Vss)

    Full Information

    First Posted
    November 12, 2015
    Last Updated
    February 3, 2022
    Sponsor
    Baxalta now part of Shire
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02605525
    Brief Title
    Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy
    Official Title
    A Phase 2 Study to Assess the Efficacy and Safety of Intravenous Infusion With Human Soluble Recombinant Fc-gamma Receptor IIB (SM101/BAX 1810) in Subjects With Immunoglobulin A Nephropathy (IgAN)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2021
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    December 31, 2015 (Actual)
    Primary Completion Date
    November 30, 2016 (Anticipated)
    Study Completion Date
    November 30, 2016 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Baxalta now part of Shire

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to assess the efficacy and safety of SM101 in the treatment of Immunoglobulin A nephropathy (IgAN)

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Immunoglobulin A Nephropathy
    Keywords
    IgAN

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    SM101 12 mg/kg
    Arm Type
    Experimental
    Arm Description
    Human soluble recombinant Fcγ Receptor IIB
    Arm Title
    SM101 24 mg/kg
    Arm Type
    Experimental
    Arm Description
    Human soluble recombinant Fcγ Receptor IIB
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    L-histidine-buffered saline with mannitol, sucrose, and polysorbate 2
    Intervention Type
    Biological
    Intervention Name(s)
    SM101
    Other Intervention Name(s)
    BAX1810, BAX 1810
    Intervention Description
    Human soluble recombinant Fcγ Receptor IIB
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    L-histidine-buffered saline with mannitol, sucrose, and polysorbate 20
    Primary Outcome Measure Information:
    Title
    Percent change in proteinuria from Baseline to Week 24
    Time Frame
    Baseline and Week 24
    Secondary Outcome Measure Information:
    Title
    Number of participants who demonstrate a ≥30% reduction from Baseline in proteinuria
    Time Frame
    Baseline, Week 8, Week 12, Week 18, and Week 24
    Title
    Number of participants who reach and maintain proteinuria levels below 1.0 g/24 h
    Time Frame
    Week 8, Week 12, Week 18, and Week 24
    Title
    Mean change from Baseline in Estimated glomerular filtration rate (eGFR)
    Time Frame
    Baseline, Week 8, Week 12, Week 18, and Week 24
    Title
    Number of participants who experience any treatment-related serious adverse event (SAE) or severe adverse events (AE) during the course of the treatment period or subsequent follow-up period
    Time Frame
    Throughout the study period of approximately 19 months
    Title
    Number of participants who experience serious adverse events (SAEs) or adverse events (AEs)
    Time Frame
    Throughout the study period of approximately 19 months
    Title
    Number of participants who experience temporally-related adverse events (AEs)
    Description
    Temporally-related AEs - defined as AEs occurring during investigational product (IP) administration or within 72 hours of IP administration, regardless of causality
    Time Frame
    Baseline through 72 hours of IP administration
    Title
    Number of participants with any clinically significant change in vital signs during investigational product (IP) administration or within 30 minutes following administration
    Time Frame
    Baseline through 30 minutes following IP administration
    Title
    Number of infusions associated with adverse events (AEs) or serious adverse events (SAEs) , regardless of causality
    Time Frame
    Throughout the study period of approximately 19 months
    Title
    Number of infusions that had to be slowed, interrupted, or terminated due to adverse events (AEs) or serious adverse events (SAEs)
    Time Frame
    Throughout the study period of approximately 19 months
    Title
    Number of participants with detectable levels of antidrug antibodies (ADAs)
    Time Frame
    Baseline, Week 3, Week 4, Week 12, Week 24, or early termination from the study
    Title
    Clinically significant abnormal laboratory assessments
    Time Frame
    Throughout the study period of approximately 19 months
    Title
    Pharmacokinetics: maximum observed concentration (Cmax)
    Time Frame
    Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.
    Title
    Pharmacokinetics: time of maximum observed concentration (Cmax)
    Time Frame
    Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.
    Title
    Pharmacokinetics: area under the concentration-time curve during a dosing interval (AUC(0-tau))
    Time Frame
    Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.
    Title
    Pharmacokinetics: terminal half-life (t1/2)
    Time Frame
    Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.
    Title
    Pharmacokinetics: systemic clearance (CL)
    Time Frame
    Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.
    Title
    Pharmacokinetics: volume of distribution at the terminal phase (Vz)
    Time Frame
    Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.
    Title
    Pharmacokinetics: volume of distribution at steady state (Vss)
    Time Frame
    Week 1 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 8 or 12, 24, 48 or 72, and 168 hours. Week 4 within 30 minutes pre-infusion, and post-infusion 0.5, 1, 2, 4, 24, and 168 hours.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 18 years of age or older at the time of screening Participant may be of any race or ethnicity Participant must have a biopsy-proven diagnosis of IgAN. Participant's blood pressure is ≤130/80 mmHg at Screening Participant is on maximally tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) for at least 3 months prior to the baseline visit. Participant must present at screening with current proteinuria levels between 1 g/24 h and 3.5 g/24 h, based on spot urine protein-to-creatinine ratio (UPCR) Participant must present at screening with an estimated glomerular filtration rate (eGFR) >40mL/min/1.73m^2 If a female of childbearing potential, participant must have a negative pregnancy test at screening, is not currently breastfeeding, and agrees to employ adequate birth control measures for the duration of the study. Male participants with female partners of childbearing potential must agree to use adequate birth control measures for the duration of the study Participant is willing and able to comply with the requirements of this protocol and agrees to sign an informed consent form prior to any study-related activities Exclusion Criteria: Participant has a history or current evidence of renal disease other than IgAN Participants with evidence of rapidly progressive disease Participant has IgAN with histologic evidence of advanced tubular atrophy and interstitial History or current evidence of other autoimmune disease History or current evidence of any chronic or uncontrolled medical condition which could, in the opinion of the Investigator, affect the participant's safety and ability to adhere to this protocol History or current evidence of a severe acute or chronic infection Use of systemic corticosteroids within 3 months prior to baseline, or anticipated use during the treatment period (Week 1 through Week 4). Note: Corticosteroids administered by inhalation or intranasally, or limited topical use of low-potency topical corticosteroids are allowed throughout the study. Known hypersensitivity or allergic reaction to any E. coli-derived recombinant product, yeast extract, or to the IP or any of its excipients Treatment with any immunomodulatory/immunosuppressive compound or monoclonal antibody for any indication within 6 months (unless otherwise stated) prior to screening (eg, B cell-depleting agents [eg, rituximab, epratuzumab] for ≥48 weeks; B-cell modifying agents [eg, belimumab, atacicept] for ≥24 weeks; IV immunoglobulins for ≥12 weeks and all other immunosuppressive treatments [eg, methotrexate, cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine] for ≥12 weeks) Clinically significant laboratory abnormalities prior to baseline History of any malignancy within past 5 years prior to screening (except for basal and squamous cell carcinomas of the skin, in situ cervical cancer, and stable prostate cancer that does not require treatment) History of tonsillectomy within 2 months prior to screening Participation in another clinical study involving an IP or investigational device within 30 days prior to screening or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study Participant is a family member or employee of the Investigator A female participant who is pregnant or nursing at the time of screening
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Study Director
    Organizational Affiliation
    Takeda
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy

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