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

• ClinicalTrials.gov Identifier: NCT04456816
• Recruitment Status: Recruiting
• First Posted: July 7, 2020
• Last Update Posted: September 22, 2021
• Sponsor: SynAct Pharma Aps
• Information provided by (Responsible Party): SynAct Pharma Aps

Tracking Information

• First Submitted Date: June 24, 2020
• First Posted Date: July 7, 2020
• Last Update Posted Date: September 22, 2021
• Actual Study Start Date: August 31, 2020
• Estimated Primary Completion Date: November 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 13, 2020)

• Adverse Event [ Time Frame: Week 4 ]
  Evaluation of Adverse Event
• Serious Adverse Events [ Time Frame: Week 4 ]
  Evaluation of Serious Adverse Events
• ALAT change in plasma samples [ Time Frame: Week 4 ]
  Evaluation of ALAT compared with baseline
• ASAT change in plasma samples [ Time Frame: Week 4 ]
  Evaluation of ASAT compared with baseline
• Total bilirubin change in plasma samples [ Time Frame: Week 4 ]
  Evaluation of total bilirubin compared with baseline
• Alkaline phosphatase change in plasma samples [ Time Frame: Week 4 ]
  Evaluation of alkaline phosphatase compared with baseline
• Protein change in 24 hours urinary protein excretion [ Time Frame: Week 4 ]
  Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion

Original Primary Outcome Measures (submitted: June 30, 2020)

• Adverse Event [ Time Frame: Week 4 ]
  Evaluation of Adverse Event
• Serious Adverse Events [ Time Frame: Week 4 ]
  Evaluation of Serious Adverse Events
• Laboratorie assessment ALAT [ Time Frame: Week 4 ]
  Evaluation of ALAT compared with baseline
• Laboratorie assessment ASAT [ Time Frame: Week 4 ]
  Evaluation of ASAT compared with baseline
• Laboratorie assessment total bilirubin [ Time Frame: Week 4 ]
  Evaluation of total bilirubin compared with baseline
• Laboratorie assessment alkaline phosphatase [ Time Frame: Week 4 ]
  Evaluation of alkaline phosphatase compared with baseline
• Protein change in 24 hours urinary protein excretion [ Time Frame: Week 4 ]
  Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion

Current Secondary Outcome Measures (submitted: June 30, 2020)

Albumin change in 24 hours urinary protein excretion [ Time Frame: Week 4 ]

Change of albumin in urine excretion compared to baseline measured in 24 h urinary protein excretion

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN
• 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 4 Weeks as an add-on to Patients, in ACE Inhibitor or Angiotensin II Receptor Blocker Treatment, With Idiopathic Membranous Nephropathy
• 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) 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) 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 4 weeks (28 days) as an add-on to any ongoing treatment, including ACE inhibitors/ angiotensin II receptor blocker
• Group B (6 subjects): placebo for 4 weeks (28 days) as an add-on to any ongoing treatment including ACE inhibitors/ angiotensin II receptor blocker.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Exploratory, randomized, double-blind, multi-center, placebo-controlled 4-week study with repeated doses of AP1189

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Idiopathic Membranous Nephropathy

Intervention

• Drug: 100 mg AP1189
  100 mg AP1189 powder in bottle. The dose of 100 mg AP1189 is selected as the starting dose, though with the opportunity to adjust the dose, based on a blinded evaluation of the pharmacokinetics results following dosing of the first 9 subjects.
• Drug: Placebo
  Placebo powder in bottle

Study Arms

• Experimental: 100 mg AP1189
  100 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water.
  Intervention: Drug: 100 mg AP1189
• Experimental: Placebo
  Placebo. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension i e. the powder will be added 50 ml water.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 30, 2020): 23
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: November 1, 2022 (Final data collection date for primary outcome measure)

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 and based on a renal biopsy
• Diagnosed as anti-PLA2-Receptor positive by local laboratory within 6 months prior to inclusion
• Nephrotic syndrome defined by a U-protein/creatinine ratio >3.5 g/g and/or U-albumin/creatinine ratio >2.2 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 2 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
• 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

Exclusion Criteria:

• Participation in any other study involving investigational drug(s) during the study and within 4 weeks prior to study entry
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT04456816
• Other Study ID Numbers: SynAct-CS003
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: SynAct Pharma Aps
• Study Sponsor: SynAct Pharma Aps
• Collaborators: Not Provided

Investigators

• Principal Investigator: Henrik Birn, Professor; Aarhus Universitetshospital

• PRS Account: SynAct Pharma Aps
• Verification Date: September 2021