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

November 20, 2023 updated by: SynAct Pharma Aps

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Estimated)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Aarhus, Denmark, 8200
        • Recruiting
        • Aarhus Universitetshospital
        • Contact:
          • Henrik Birn, Professor
          • Phone Number: +45 40460271
          • Email: henrbirn@rm.dk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 100 mg AP1189
100 mg AP1189. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
100 mg AP1189 tablet
Experimental: Placebo
Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
Matching placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Event
Time Frame: Week 12
Evaluation of Adverse Event
Week 12
Serious Adverse Events
Time Frame: Week 12
Evaluation of Serious Adverse Events
Week 12
ALAT change in plasma samples
Time Frame: Week 12
Evaluation of ALAT compared with baseline
Week 12
ASAT change in plasma samples
Time Frame: Week 12
Evaluation of ASAT compared with baseline
Week 12
Total bilirubin change in plasma samples
Time Frame: Week 12
Evaluation of total bilirubin compared with baseline
Week 12
Alkaline phosphatase change in plasma samples
Time Frame: Week 12
Evaluation of alkaline phosphatase compared with baseline
Week 12
Protein change in 24 hours urinary protein excretion
Time Frame: Week 12
Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Albumin change in 24 hours urinary protein excretion
Time Frame: Week 12
Change of albumin in urine excretion compared to baseline measured in 24 h urinary protein excretion
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Henrik Birn, Professor, Aarhus Universitetshospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2020

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

June 24, 2020

First Submitted That Met QC Criteria

June 30, 2020

First Posted (Actual)

July 7, 2020

Study Record Updates

Last Update Posted (Estimated)

November 21, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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