RESOMELAGON for Idiopathic membranous nephropathy | Nephrotic syndrome

Inclusion criteria

• {"criterion_text":"- Written informed consent has been obtained prior to initiating any study-specific procedures"}
• {"criterion_text":"- Male and female subjects, 18 to 85 years of age with iMN and severe proteinuria"}
• {"criterion_text":"- Diagnosed as anti-PLA2-Receptor positive by local laboratory within 6 months prior to inclusion and/or having a renal biopsy consistent with iMN within 24 months of inclusion"}
• {"criterion_text":"- Severe proteinuria defined by a U-protein/creatinine ratio >3.0 g/g and/or U-albumin/creatinine ratio >2.0 g/g and P-albumin below the lower normal limit"}
• {"criterion_text":"- eGFR > 30 ml/min/1.73m2"}
• {"criterion_text":"- Treatment with ACE- inhibitors or angiotensin II receptor blocker for a minimum of 1 month 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"}
• {"criterion_text":"- ONLY DENNMARK AND NORWAY: Females of child-bearing potential using reliable means of contraception (for detailed information see section 17.8) or are postmenopausal (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)"}
• {"criterion_text":"- ONLY DENNMARK AND NORWAY: Females of childbearing potential with negative pregnancy test at screening and baseline"}
• {"criterion_text":"- ONLY SWEDEN: Post-menopausal women (menstrual periods stopped at least 12 months ahead of the enrolment in the trial) or women who are surgically sterilized (the procedure must have been performed at least 6 months prior to screening)"}

Exclusion criteria

• {"criterion_text":"- Participation in any other study involving investigational drug(s) during the study and within 4 weeks prior to study entry"}
• {"criterion_text":"- Pregnant women or nursing (breastfeeding) mothers"}
• {"criterion_text":"- History of alcohol, drug, or chemical abuse within the 6 months prior to screening"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- ONLY SWEDEN: Females of child-bearing potential"}
• {"criterion_text":"- Clinical findings that in the opinion of the investigator would suggest condition(s) other than iMN as a major cause of severe proteinuria"}
• {"criterion_text":"- Major surgery within 8 weeks prior to screening or planned surgery within one month following randomization"}
• {"criterion_text":"- 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\""}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Treated with rituximab within 12 months of screening"}
• {"criterion_text":"- Evidence of active malignant disease (except basal cell carcinoma of the skin that has been excised and cured)."}
• {"criterion_text":"- Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids"}
• {"criterion_text":"- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease"}

Primary endpoints

• {"endpoint_text":"- To compare the safety of AP1189 against placebo by evaluating adverse events (AEs), serious adverse events (SAEs), vital signs, electrocardiograms and laboratory abnormalities.","definition_or_measurement_approach":"Safety assessed by recording and evaluating AEs, SAEs, vital signs, ECGs and laboratory abnormalities."}
• {"endpoint_text":"- The result of 12 weeks of treatment on 24 hours urinary protein excretion as expressed as changes in urine excretion from baseline to the end of the twelve weeks treatment period (baseline is defined as 24 h urinary protein excretion determined prior to dosing with AP1189 or placebo).","definition_or_measurement_approach":"Efficacy measured as change in 24-hour urinary protein excretion from baseline (24 h urinary protein measured prior to dosing) to end of 12-week treatment period."}

Secondary endpoints

• {"endpoint_text":"- The result of 12 weeks of treatment on 24 hours urinary albumin excretion as expressed as changes in urine excretion from baseline to the end of the twelve weeks treatment period (baseline is defined as 24 h urinary albumin excretion determined prior to dosing with AP1189 or placebo)","definition_or_measurement_approach":"Change in 24-hour urinary albumin excretion from baseline to end of 12 weeks."}
• {"endpoint_text":"- The result of 12 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 (ΔFEAlb = FEAlb, four weeks- FEAlb, baseline)","definition_or_measurement_approach":"FEAlb defined as (Clearance of Albumin / Clearance of Creatinine) x 100; changes expressed as percentage change from baseline."}
• {"endpoint_text":"- The result of 12 weeks of treatment on changes in plasma albumin from baseline to the end of the twelve weeks treatment period","definition_or_measurement_approach":"Change in plasma (P-) albumin from baseline to end of 12 weeks."}
• {"endpoint_text":"- 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. Partial 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.","definition_or_measurement_approach":"Remission definitions provided: Complete remission = urinary protein <0.3 g/d with normal P-albumin and P-creatinine; Partial remission = urinary protein <3.5 g/d and ≥50% reduction from peak with improved/normalized P-albumin and stable P-creatinine. Measured at last day of treatment and 4 weeks post-dose."}
• {"endpoint_text":"- The result of 12 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 twelve weeks treatment period","definition_or_measurement_approach":"Change in estimated GFR (from P-creatinine and P-cystatin C) from baseline to end of 12 weeks."}
• {"endpoint_text":"- The result of 12 weeks of treatment on 24 hours urinary creatinine clearance CCr expressed as changes in CCr from baseline to the end of the twelve weeks treatment period","definition_or_measurement_approach":"Change in 24-hour urinary creatinine clearance (CCr) from baseline to end of 12 weeks."}
• {"endpoint_text":"- Changes in the above-defined parameters (urinary protein/albumin, Palbumin, GFR and CCr) at the four weeks post-dosing follow up visit, compared to the values at the end of dosing and baseline.","definition_or_measurement_approach":"Changes in urinary protein/albumin, P-albumin, GFR and CCr at 4 weeks post-dosing compared to end-of-dosing and baseline."}

Denmark

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

27-10-2024

Processing Time Days

11

Number Of Sites

4

Number Of Participants

12

Sweden

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

28-10-2024

Processing Time Days

12

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Synact Pharma ApS

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"CroxxMed ApS","duties_or_roles":[1,10,11,12,5,6],"organisation_type":"Industry"}