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Withdrawn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
About this trial
This is an interventional treatment trial for Immunoglobulin A Nephropathy focused on measuring IgAN
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
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
NCT ID
NCT02605525
First Posted
November 12, 2015
Last Updated
February 3, 2022
Sponsor
Baxalta now part of Shire
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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