Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy, Severe Proteinuria Due to Idiopathic Membranous Nephropathy
Conditions
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.
Interventions
DRUG100 mg AP1189
100 mg AP1189 tablet
DRUGPlacebo
Matching placebo tablet
Sponsors
SynAct Pharma Aps
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Exploratory, randomized, double-blind, multi-center, placebo-controlled 12-weeks study with repeated doses of AP1189
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | Week 12 | Evaluation of Adverse Event |
| Serious Adverse Events | Week 12 | Evaluation of Serious Adverse Events |
| ALAT change in plasma samples | Week 12 | Evaluation of ALAT compared with baseline |
| ASAT change in plasma samples | Week 12 | Evaluation of ASAT compared with baseline |
| Total bilirubin change in plasma samples | Week 12 | Evaluation of total bilirubin compared with baseline |
| Alkaline phosphatase change in plasma samples | Week 12 | Evaluation of alkaline phosphatase compared with baseline |
| Protein change in 24 hours urinary protein excretion | Week 12 | Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Albumin change in 24 hours urinary protein excretion | Week 12 | Change of albumin in urine excretion compared to baseline measured in 24 h urinary protein excretion |
Countries
Denmark
Contacts
CONTACTIrene Sandholdt
CONTACTBirgitte Telmer, MD
PRINCIPAL_INVESTIGATORHenrik Birn, Professor
Aarhus University Hospital
Outcome results
None listed