A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria
Primary Purpose
Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy, Severe Proteinuria Due to Idiopathic Membranous Nephropathy
Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
100 mg AP1189
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy
Eligibility Criteria
Inclusion Criteria:
- Written informed consent has been obtained prior to initiating any study-specific procedures
- Male and female subjects, 18 to 85 years of age diagnosed with iMN within 6 months prior to inclusion
- Diagnosed as anti-PLA2-Receptor positive by local laboratory within 6 months prior to inclusion
- Severe proteinuria defined by a U-protein/creatinine ratio >3.0 g/g and/or U-albumin/creatinine ratio >2.0 g/g and a P-albumin below the lower normal limit
- eGFR > 30 ml/min/1.73m2
- Treated with ACE- inhibitors or angiotensin II receptor blocker for a minimum of 1 months with a stable systemic arterial blood pressure OR treatment with ACE inhibitors and/or angiotensin receptor blocker was excluded or discontinued due to hypotension, intolerance or other side effect
Only Denmark and Norway:
- Females of child-bearing potential using reliable means of contraception or are post-menopausal
- Females of childbearing potential with negative pregnancy test at screening and baseline
Only Sweden:
- Post-menopausal women or women who are surgically sterilized.
Exclusion Criteria:
- Participation in any other study involving investigational drug(s) during the study and within 4 weeks prior to study entry
- Clinicial findings that in the opinion of the investigator would suggest condition(s) other than iMN as a major cause of severe proteinuria
- Major surgery within 8 weeks prior to screening or planned surgery within 1 month following randomization
- Blood pressure with systolic pressure above 160 mmHg and/or diastolic pressure above 100 mmHg despite antihypertensive treatment will in all cases be considered "uncontrolled"
- Treated with systemic corticosteroids, or other immune suppressive, or immune modulating compounds within 4 weeks prior to screening and during the entire treatment period and until the final visit
- Treated with rituximab within 12 months of screening
- Evidence of active malignant disease
- Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disease
- Pregnant women or nursing mothers
- History of alcohol, drug, or chemical abuse within the 6 months prior to screening
- Any condition that in the view of the investigator would suggest that the patient is unable to comply with study protocol and procedures
Only Sweden:
- Females of child-bearing potential.
Sites / Locations
- Aarhus UniversitetshospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
100 mg AP1189
Placebo
Arm Description
100 mg AP1189. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
Outcomes
Primary Outcome Measures
Adverse Event
Evaluation of Adverse Event
Serious Adverse Events
Evaluation of Serious Adverse Events
ALAT change in plasma samples
Evaluation of ALAT compared with baseline
ASAT change in plasma samples
Evaluation of ASAT compared with baseline
Total bilirubin change in plasma samples
Evaluation of total bilirubin compared with baseline
Alkaline phosphatase change in plasma samples
Evaluation of alkaline phosphatase compared with baseline
Protein change in 24 hours urinary protein excretion
Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion
Secondary Outcome Measures
Albumin change in 24 hours urinary protein excretion
Change of albumin in urine excretion compared to baseline measured in 24 h urinary protein excretion
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04456816
Brief Title
A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria
Official Title
An Exploratory, Randomized, Double-blind, Multicenter, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AP1189 Versus Placebo Administered for 12 Weeks as an add-on to Patients, in ACE Inhibitor or Angiotensin II Receptor Blocker Treatment, With Idiopathic Membranous Nephropathy and Severe Proteinuria
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SynAct Pharma Aps
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study with repeated doses of AP1189. The study population will consist of patients with idiopathic membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin II receptor blocker treatment.
Detailed Description
This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study with repeated doses of AP1189. The study population will consist of patients with idiopathic membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin II receptor blocker treatment.
Following a successful screening, subjects who fulfill the enrollment criteria will be randomized in a 2:1 ratio in group A and B:
Group A (12 subjects): AP1189 dose 100 mg, once daily for 12 weeks (28 days) as an add-on to any ongoing treatment, including ACE inhibitors/ angiotensin II receptor blocker
Group B (6 subjects): placebo for 12 weeks (28 days) as an add-on to any ongoing treatment including ACE inhibitors/ angiotensin II receptor blocker.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy, Severe Proteinuria Due to Idiopathic Membranous Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Exploratory, randomized, double-blind, multi-center, placebo-controlled 12-weeks study with repeated doses of AP1189
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
100 mg AP1189
Arm Type
Experimental
Arm Description
100 mg AP1189. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
Intervention Type
Drug
Intervention Name(s)
100 mg AP1189
Intervention Description
100 mg AP1189 tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo tablet
Primary Outcome Measure Information:
Title
Adverse Event
Description
Evaluation of Adverse Event
Time Frame
Week 12
Title
Serious Adverse Events
Description
Evaluation of Serious Adverse Events
Time Frame
Week 12
Title
ALAT change in plasma samples
Description
Evaluation of ALAT compared with baseline
Time Frame
Week 12
Title
ASAT change in plasma samples
Description
Evaluation of ASAT compared with baseline
Time Frame
Week 12
Title
Total bilirubin change in plasma samples
Description
Evaluation of total bilirubin compared with baseline
Time Frame
Week 12
Title
Alkaline phosphatase change in plasma samples
Description
Evaluation of alkaline phosphatase compared with baseline
Time Frame
Week 12
Title
Protein change in 24 hours urinary protein excretion
Description
Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Albumin change in 24 hours urinary protein excretion
Description
Change of albumin in urine excretion compared to baseline measured in 24 h urinary protein excretion
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent has been obtained prior to initiating any study-specific procedures
Male and female subjects, 18 to 85 years of age diagnosed with iMN within 6 months prior to inclusion
Diagnosed as anti-PLA2-Receptor positive by local laboratory within 6 months prior to inclusion
Severe proteinuria defined by a U-protein/creatinine ratio >3.0 g/g and/or U-albumin/creatinine ratio >2.0 g/g and a P-albumin below the lower normal limit
eGFR > 30 ml/min/1.73m2
Treated with ACE- inhibitors or angiotensin II receptor blocker for a minimum of 1 months with a stable systemic arterial blood pressure OR treatment with ACE inhibitors and/or angiotensin receptor blocker was excluded or discontinued due to hypotension, intolerance or other side effect
Only Denmark and Norway:
Females of child-bearing potential using reliable means of contraception or are post-menopausal
Females of childbearing potential with negative pregnancy test at screening and baseline
Only Sweden:
Post-menopausal women or women who are surgically sterilized.
Exclusion Criteria:
Participation in any other study involving investigational drug(s) during the study and within 4 weeks prior to study entry
Clinicial findings that in the opinion of the investigator would suggest condition(s) other than iMN as a major cause of severe proteinuria
Major surgery within 8 weeks prior to screening or planned surgery within 1 month following randomization
Blood pressure with systolic pressure above 160 mmHg and/or diastolic pressure above 100 mmHg despite antihypertensive treatment will in all cases be considered "uncontrolled"
Treated with systemic corticosteroids, or other immune suppressive, or immune modulating compounds within 4 weeks prior to screening and during the entire treatment period and until the final visit
Treated with rituximab within 12 months of screening
Evidence of active malignant disease
Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disease
Pregnant women or nursing mothers
History of alcohol, drug, or chemical abuse within the 6 months prior to screening
Any condition that in the view of the investigator would suggest that the patient is unable to comply with study protocol and procedures
Only Sweden:
Females of child-bearing potential.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Irene Sandholdt
Phone
+45 2015 7033
Email
isa@croxxmed.com
First Name & Middle Initial & Last Name or Official Title & Degree
Birgitte Telmer, MD
Phone
+45 2015 1221
Email
bte@croxxmed.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henrik Birn, Professor
Organizational Affiliation
Aarhus Universitetshospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus Universitetshospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henrik Birn, Professor
Phone
+45 40460271
Email
henrbirn@rm.dk
12. IPD Sharing Statement
Learn more about this trial
A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria
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