A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria

NCT ID: NCT04456816

Last Updated: 2024-12-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-31
• Study Completion Date: 2026-06-30

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.

Conditions

Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy; Severe Proteinuria Due to Idiopathic Membranous Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

100 mg AP1189

100 mg AP1189. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet

Group Type: EXPERIMENTAL

100 mg AP1189

Intervention Type: DRUG

100 mg AP1189 tablet

Placebo

Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo tablet

Interventions

100 mg AP1189

100 mg AP1189 tablet

Intervention Type: DRUG

Placebo

Matching placebo tablet

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SynAct Pharma Aps

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Henrik Birn, Professor

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital

Locations

Aarhus Universitetshospital

Aarhus, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Irene Sandholdt

Role: CONTACT

Phone: +45 2015 7033

Email: isa@croxxmed.com

Birgitte Telmer, MD

Role: CONTACT

Phone: +45 2015 1221

Email: bte@croxxmed.com

Facility Contacts

Henrik Birn, Professor

Role: primary

Other Identifiers

SynAct-CS003

Identifier Type: -

Identifier Source: org_study_id