Idiopathic membranous nephropathy MedDRA version: 21.1 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 21.1 Level: PT Classification code 10029164 Term: Nephrotic syndrome System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
SynAct Pharma ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent has been obtained prior to initiating any study-specific procedures 2.Male and female subjects, 18 to 85 years of age with a renal biopsy consistent with iMN 3.Diagnosed as anti-PLA2-Receptor positive by local laboratory 4.Nephrotic syndrome defined by a U-protein/creatinine ratio >3.5 g/g and/or U-albumin/creatinine ratio >2.2 g/g and P-albumin below the lower normal limit 5.eGFR > 30 ml/min/1.73m2 6.Treated with ACE- inhibitors or angiotensin II receptor blocker for a minimum of 2 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 effects 7.Females of child-bearing potential using reliable means of contraception (for detailed information see section 22.8) or are post-menopausal (menstrual periods stopped at least 12 months ahead of the enrolment in the trial) or are surgically sterilized (the procedure must have been performed at least 6 months prior to screening) 8.Females of childbearing potential with negative pregnancy test at screening and baseline Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: 1.Participation in any other study involving investigational drug(s) during the study and within 4 weeks prior to study entry 2.Major surgery within 8 weeks prior to screening or planned surgery within one month following randomization 3.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” 4.Treated with systemic (oral, intramuscular or IV) corticosteroids, or other immune suppressive, or immune modulating compounds within 4 weeks (8 weeks for IV cyclophosphamide) prior to screening (and during the entire treatment period and until the final visit) 5.Treated with rituximab within 12 months of screening 6.Evidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured). 7.Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids 8.Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease 9.Pregnant women or nursing (breastfeeding) mothers 10.History of alcohol, drug, or chemical abuse within the 6 months prior to screening 11.Any condition that in the view of the investigator would suggest that the patient is unable to comply with study protocol and procedures (e.g., psychiatric disorders, dementia) 12. Any history of sensitivity to the IMP ingredients sucralose, starch, tartrazine, and microcrystalline cellulose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the safety of AP1189 against placebo by evaluating adverse events (AEs), serious adverse events (SAEs), vital signs, electrocardiograms and laboratory abnormalities. The result of 4 weeks of treatment on 24 hours urinary protein excretion as expressed as changes in urine excretion from baseline to the end of the four weeks treatment period (baseline is defined as 24 h urinary protein excretion determined prior to dosing with AP1189 or placebo);Secondary Objective: Result of 4 weeks treatment (Baseline to end of 4 weeks): On 24 hours urinary albumin excretion, expressed as changes in urine excretion. On fractional urine excretion of albumin (FEAlb) compared to baseline where changes in FEAlb is expressed in % compared to baseline levels. On changes in plasma albumin. No of subjects showing partial/complete remission (defined in the protocol) on the last day of treatment and four weeks after the last dose administered. On estimated GFR (eGFR) expressed as changes in GFR. On 24 hours urinary creatinine clearance CCr expressed as changes in CCr. Changes in urinary protein/albumin, P-albumin, eGFR and CCr at the four weeks post-dosing follow up visit, compared to the values at the end of dosing and baseline. The pharmacokinetic of AP1189 following the first and last day of dosing. ;Primary end point(s): Primary Safety Objective and Endpoints: To compare the safety of AP1189 against placebo by evaluating adverse events (AEs), serious adverse events (SAEs), vital signs, electrocardiograms and laboratory abnormalities. Primary Efficacy Objective and Endpoints: The result of 4 weeks of treatment on 24 hours urinary protein excretion as expressed as changes in urine excretion from baseline to the end of the four weeks treatment period (baseline is defined as 24 h urinary protein excretion determined prior to dosing with AP1189 or placebo). ;Timepoint(s) of evaluation of this end point: AE and SAE will be registered at all visits/phone calls and | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •The result of 4 weeks of treatment on 24 hours urinary albumin excretion as expressed as changes in urine excretion from baseline to the end of the four weeks treatment period (baseline is defined as 24 h urinary albumin excretion determined prior to dosing with AP1189 or placebo) •The result of 4 weeks of treatment on fractional urine excretion of albumin (FEAlb) compared to baseline (where FEAlb is defined as Clearance of Albumin/Clearance of Creatinine expressed in %; (FEAlb=CAlb/ CCr x 100)) where changes in FEAlb is expressed in % compared to baseline levels (?FEAlb = FEAlb, four weeks- FEAlb, baseline) •The result of 4 weeks of treatment on changes in plasma albumin from baseline to the end of the four weeks treatment period •The number of subjects who show partial or complete remission on the last day of treatment and four weeks after the last dose administered, defined as: oComplete Remission: Urinary protein excretion <0.3 g/d accompanied by a normal P-albumin concentration, and a normal P-creatinine value oPartial Remission: Urinary protein excretion <3.5 g/d and a 50% or greater reduction from peak values accompanied by an improvement or normalization of the P-albumin concentration and stable P-creatinine value •The result of 4 weeks of treatment on estimated GFR calculated from both P-creatinine and P-cystatin C expressed as changes in GFR from baseline to the end of the four weeks treatment period •The result of 4 weeks of treatment on 24 hours urinary creatinine clearance CCr expressed as changes in CCr from baseline to the end of the four weeks treatment period •Changes in the above-defined parameters (urinary protein/albumin, P-albumin, GFR and CCr) at the four weeks post-dosing follow up visit, compared to the values at the end of dosing and baseline •The pharmacokinetic parameters of AP1189 following the first and last day of dosing: oPharmacokinetic parameters (Cmax, tmax, AUC0-t, AUC0-24, AUC0-8 (Day 1 only), Ke, and te) | — |
Countries
Denmark, Norway
Contacts
Public ContactCSO
SynAct Pharma ApS
Outcome results
None listed