Multiple Doses of DM199 in Patients With Chronic Kidney Disease (REDUX)

A Multi-Center Open-label Investigation to Assess the Safety and Efficacy of Multiple Doses of DM199 in Patients With Chronic Kidney Disease

An open-label, Phase II, multi-center study evaluating multiple doses of DM199 in participants with chronic kidney disease.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases
• Intervention / Treatment: Drug: DM199

Detailed Description

This is an open-label, Phase II, multi-center study evaluating DM199 in approximately 90 Participants in three cohorts.

Cohort I: African Americans with CKD (Stage II or III), hypertension and non-diabetic Cohort II: Participants with IgA nephropathy diagnosis and CKD (Stage II or III) Cohort III: Diabetes Mellitus (Type II) with CKD (Stage II or III) and hypertension

Participants in each cohort will be enrolled in a parallel assignment to one of two doses:

Dose 1: DM199 2.0 µg/kg SC 2x week for 95 days Dose 2: DM199 5.0 µg/kg SC 2x week for 95 days

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85210
      • Aventiv Research
  • California
    • Granada Hills, California, United States, 91334
      • Amcis Research Center
    • Los Angeles, California, United States, 90033
      • IMD Clinical Trials Inc
    • Northridge, California, United States, 91324
      • Amicis Reserch Center
  • Florida
    • Coral Springs, Florida, United States, 33067
      • Innovative Healthcare Institute
    • Fort Lauderdale, Florida, United States, 33308
      • Elixia at Florida Kidney Physicians-SE
    • Hollywood, Florida, United States, 33024
      • Pines Clinical Research-Hollywood
    • Temple Terrace, Florida, United States, 33637
      • Elixia at Florida Kidney Physicians
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Boise Kidney & Hypertension Institute
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research, an AMR Company
  • Pennsylvania
    • Upland, Pennsylvania, United States, 19013
      • Elixia At Clincal Renal Associates
  • Texas
    • Dallas, Texas, United States, 75231
      • Nephrotex Research Group, LLC
    • DeSoto, Texas, United States, 75115
      • RDRI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Cohort I

• African American
• Hypertension as defined by the American Heart Association for Stage I hypertension where systolic blood pressure (BP) ≥130 mmHg or diastolic BP ≥ 80 mmHg or on medication for treatment of hypertension.

Cohort II

• IgA nephropathy confirmed by medical history with biopsy

Cohort III

• Diabetes Mellitus (Type 2) with hypertension where systolic blood pressure (BP) ≥130 mmHg or diastolic BP ≥ 80 mmHg or on medication for treatment of hypertension
• Hemoglobin A1c ≥7% at screening

Both Cohorts

• Participant is willing and able to provide informed consent for study participation
• Participant male or female ≥ 18 years of age
• Participant has CKD as defined by using CKD EPI for Stage II 60 to <90 mL/min/1.73 m2 or Stage III 30 to <60 mL/min/1.73 m2
• UACR >150 mg/g and <5000 mg/g at screening
• Participant is clinically stable with respect to underlying renal impairment as assessed by the Investigator's medical evaluation

Exclusion Criteria:

• Participant has positive drug test for drugs of abuse and/or positive alcohol breath test at screening and Day 1
• Participant has a current diagnosis and/or is taking medication or diet control for diabetes (cohort I and II only)
• Participant has an A1c > 7% at screening (cohort I and II only)
• Participant received corticosteroid therapy within last 3 months
• Participant is unable or unwilling to comply with protocol requirements, including assessments, tests, and follow-up visits
• Participant has a history of significant allergic diathesis such as urticaria, angioedema, or anaphylaxis
• Participant has been previously diagnosed with kidney disease other than for hypertension, IgA or Diabetes Mellitus (Type II)
• Participant has hypotension as defined by systolic blood pressure ≤ 90 mmHg and diastolic blood pressure ≤ 60 mmHg at screen
• ACEi or GLP-1 medication prescribed for and taken by Participant (must not be taking for 5 half-lives prior to study drug administration and for 10 days post study drug administration)
• Participant has a current malignancy or active malignancy ≤ 2 years prior to enrollment except basal cell or squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy and ≥ 6 months have elapsed since the procedure
• Participant has an active infection at the time of enrollment, and/or a history of clinically significant acute bacterial, viral, or fungal systemic infections that required systemic treatment with a completed therapy in the last 7 days prior to enrollment
• Participant has known medical history of alpha 1-antitrypsin deficiency (α1-antitrypsin deficiency)
• Participant is pregnant or nursing or is planning a pregnancy during the study period
• Participant is male or female of childbearing potential, is participating in sexual activity that could lead to pregnancy and is unable or unwilling to practice medically effective contraception during the study
• Participant has received any investigational drug or device within 14 days (or 5 half lives, whichever is longer) prior to study drug administration starting on Day 1
• Participant has renal artery stenosis as determined at screen with medical history
• Participant received a kidney transplant
• Participant does not have adequate venous access for blood sampling
• Participant has any other medical condition which, in the opinion of the Investigator, will make participation medically unsafe or interfere with the study results
• Participant has any other clinically significant abnormalities in laboratory test results at screening that would, in the opinion of the Investigator, increase the Participant's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
• Participant has any significant arrhythmia or conduction abnormality, which in the opinion of the Investigators and Medical Monitor may interfere with the safety of the Participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2.0 µg/kg, multiple dose; n=45 with 15 Participants from cohort 1, 15 from cohort 2, and 15 from cohort 3	Drug: DM199; A pharmaceutical formulation comprised of recombinant human tissue kallikrein-1 (rhKLK-1) that is being developed as an injectable protein drug
Experimental: 5.0 µg/kg, multiple dose; n=45 with 15 Participants from cohort 1, 15 from cohort 2 and 15 from cohort 3	Drug: DM199; A pharmaceutical formulation comprised of recombinant human tissue kallikrein-1 (rhKLK-1) that is being developed as an injectable protein drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emergent adverse events	Incidence, severity, and causality of adverse events	12 weeks
Change in renal function	eGFR	12 weeks
Change in urine albumin to creatinine ratio	UACR change from baseline	12 weeks
Plasma measurements of DM199	Maximum plasma concentration of DM199	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor necrosis factor receptor 1 (TNF R1) concentration in plasma, change from baseline	TNF R1 change from baseline	12 weeks
C-reactive protein (CRP) concentration in plasma, change from baseline	CRP change from baseline	12 weeks
Matrix metalloproteainase-9 (MMP-9) concentration in plasma, change from baseline	MMP-9 change from baseline	12 weeks
Vascular endothelial growth factor (VEGF) concentration in plasma, change from baseline	VEGF change from baseline	12 weeks
Cystatin C concentration in plasma, change from baseline	Cystatin C change from baseline	12 weeks
Prostaglandin E2 concentration in plasma, change from baseline	Prostaglandin E2 change from baseline	12 weeks
Prostacyclin concentration in plasma, change from baseline	Prostacyclin change from baseline	12 weeks

Collaborators and Investigators

• Sponsor: DiaMedica Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2019
• Primary Completion (Actual): March 16, 2022
• Study Completion (Actual): March 16, 2022

Study Registration Dates

• First Submitted: October 8, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: DM199-2019-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No