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

• ClinicalTrials.gov Identifier: NCT04456816
• Recruitment Status: Recruiting
• First Posted: July 7, 2020
• Last Update Posted: November 17, 2022
• Sponsor: SynAct Pharma Aps
• Information provided by (Responsible Party): SynAct Pharma Aps

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy; Severe Proteinuria Due to Idiopathic Membranous Nephropathy	Drug: 100 mg AP1189; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Exploratory, randomized, double-blind, multi-center, placebo-controlled 12-weeks study with repeated doses of AP1189
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 31, 2020
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

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	Drug: 100 mg AP1189; 100 mg AP1189 tablet
Experimental: Placebo; Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet	Drug: Placebo; Matching placebo tablet

Outcome Measures

Primary Outcome Measures :

1. Adverse Event [ Time Frame: Week 12 ]
   Evaluation of Adverse Event
2. Serious Adverse Events [ Time Frame: Week 12 ]
   Evaluation of Serious Adverse Events
3. ALAT change in plasma samples [ Time Frame: Week 12 ]
   Evaluation of ALAT compared with baseline
4. ASAT change in plasma samples [ Time Frame: Week 12 ]
   Evaluation of ASAT compared with baseline
5. Total bilirubin change in plasma samples [ Time Frame: Week 12 ]
   Evaluation of total bilirubin compared with baseline
6. Alkaline phosphatase change in plasma samples [ Time Frame: Week 12 ]
   Evaluation of alkaline phosphatase compared with baseline
7. 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

Secondary Outcome Measures :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Irene Sandholdt; +45 2015 7033; isa@croxxmed.com

Contact: Birgitte Telmer, MD; +45 2015 1221; bte@croxxmed.com

Locations

Denmark

Aarhus Universitetshospital; Recruiting

Aarhus, Denmark, 8200

Contact: Henrik Birn, Professor +45 40460271 henrbirn@rm.dk

Sponsors and Collaborators

SynAct Pharma Aps

Investigators

• Principal Investigator: Henrik Birn, Professor; Aarhus Universitetshospital

More Information

• Responsible Party: SynAct Pharma Aps
• ClinicalTrials.gov Identifier: NCT04456816
• Other Study ID Numbers: SynAct-CS003
• First Posted: July 7, 2020
• Last Update Posted: November 17, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Kidney Diseases; Proteinuria; Nephrotic Syndrome; Nephrosis; Glomerulonephritis, Membranous; Urologic Diseases; Urination Disorders; Urological Manifestations; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases