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

• ClinicalTrials.gov Identifier: NCT04123613
• Recruitment Status: Completed
• First Posted: October 11, 2019
• Last Update Posted: March 31, 2022
• Sponsor: DiaMedica Therapeutics Inc
• Information provided by (Responsible Party): DiaMedica Therapeutics Inc

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Kidney Diseases	Drug: DM199	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center Open-label Investigation to Assess the Safety and Efficacy of Multiple Doses of DM199 in Patients With Chronic Kidney Disease
• Actual Study Start Date: December 17, 2019
• Actual Primary Completion Date: March 16, 2022
• Actual Study Completion Date: March 16, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment emergent adverse events [ Time Frame: 12 weeks ]
   Incidence, severity, and causality of adverse events
2. Change in renal function [ Time Frame: 12 weeks ]
   eGFR
3. Change in urine albumin to creatinine ratio [ Time Frame: 12 weeks ]
   UACR change from baseline
4. Plasma measurements of DM199 [ Time Frame: 12 weeks ]
   Maximum plasma concentration of DM199

Secondary Outcome Measures :

1. Tumor necrosis factor receptor 1 (TNF R1) concentration in plasma, change from baseline [ Time Frame: 12 weeks ]
   TNF R1 change from baseline
2. C-reactive protein (CRP) concentration in plasma, change from baseline [ Time Frame: 12 weeks ]
   CRP change from baseline
3. Matrix metalloproteainase-9 (MMP-9) concentration in plasma, change from baseline [ Time Frame: 12 weeks ]
   MMP-9 change from baseline
4. Vascular endothelial growth factor (VEGF) concentration in plasma, change from baseline [ Time Frame: 12 weeks ]
   VEGF change from baseline
5. Cystatin C concentration in plasma, change from baseline [ Time Frame: 12 weeks ]
   Cystatin C change from baseline
6. Prostaglandin E2 concentration in plasma, change from baseline [ Time Frame: 12 weeks ]
   Prostaglandin E2 change from baseline
7. Prostacyclin concentration in plasma, change from baseline [ Time Frame: 12 weeks ]
   Prostacyclin change from baseline

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Aventiv Research

Mesa, Arizona, United States, 85210

United States, California

Amcis Research Center

Granada Hills, California, United States, 91334

IMD Clinical Trials Inc

Los Angeles, California, United States, 90033

Amicis Reserch Center

Northridge, California, United States, 91324

United States, Florida

Innovative Healthcare Institute

Coral Springs, Florida, United States, 33067

Elixia at Florida Kidney Physicians-SE

Fort Lauderdale, Florida, United States, 33308

Pines Clinical Research-Hollywood

Hollywood, Florida, United States, 33024

Elixia at Florida Kidney Physicians

Temple Terrace, Florida, United States, 33637

United States, Idaho

Boise Kidney & Hypertension Institute

Meridian, Idaho, United States, 83642

United States, Illinois

Research by Design LLC

Chicago, Illinois, United States, 60643

United States, Louisiana

New Orleans Center for Clinical Research, an AMR Company

New Orleans, Louisiana, United States, 70119

United States, Pennsylvania

Elixia At Clincal Renal Associates

Upland, Pennsylvania, United States, 19013

United States, Texas

Nephrotex Research Group, LLC

Dallas, Texas, United States, 75231

RDRI

DeSoto, Texas, United States, 75115

Sponsors and Collaborators

DiaMedica Therapeutics Inc

Investigators

• Study Director: Harry Alcorn, Pharm.D.; DiaMedica Inc.

More Information

• Responsible Party: DiaMedica Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT04123613
• Other Study ID Numbers: DM199-2019-001
• First Posted: October 11, 2019
• Last Update Posted: March 31, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes