Clinical trial NCT04456816: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy
Severe Proteinuria Due to Idiopathic Membranous Nephropathy
Lead sponsor: SynAct Pharma Aps
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Exploratory, randomized, double-blind, multi-center, placebo-controlled 12-weeks study with repeated doses of AP1189
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Adverse Event
timeFrame: Week 12
measure: Serious Adverse Events
timeFrame: Week 12
measure: ALAT change in plasma samples
timeFrame: Week 12
measure: ASAT change in plasma samples
timeFrame: Week 12
measure: Total bilirubin change in plasma samples
timeFrame: Week 12
measure: Alkaline phosphatase change in plasma samples
timeFrame: Week 12
measure: Protein change in 24 hours urinary protein excretion
timeFrame: Week 12
Secondary outcomes:
measure: Albumin change in 24 hours urinary protein excretion
timeFrame: Week 12
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
Study officials:
affiliation: Aarhus University Hospital
name: Henrik Birn, Professor
role: PRINCIPAL_INVESTIGATOR
References: