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

Kidney Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04123613
• Other study ID #: DM199-2019-001
• Status: Completed
• Phase: Phase 2
• Start date: December 17, 2019
• Est. completion date: March 16, 2022

Study information

• Verified date: March 2022
• Source: DiaMedica Therapeutics Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: March 16, 2022
• Est. primary completion date: March 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (a1-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

Related Conditions & MeSH terms

• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• DM199
A pharmaceutical formulation comprised of recombinant human tissue kallikrein-1 (rhKLK-1) that is being developed as an injectable protein drug

Locations

Country	Name	City	State
United States	Research by Design LLC	Chicago	Illinois
United States	Innovative Healthcare Institute	Coral Springs	Florida
United States	Nephrotex Research Group, LLC	Dallas	Texas
United States	RDRI	DeSoto	Texas
United States	Elixia at Florida Kidney Physicians-SE	Fort Lauderdale	Florida
United States	Amcis Research Center	Granada Hills	California
United States	Pines Clinical Research-Hollywood	Hollywood	Florida
United States	IMD Clinical Trials Inc	Los Angeles	California
United States	Boise Kidney & Hypertension Institute	Meridian	Idaho
United States	Aventiv Research	Mesa	Arizona
United States	New Orleans Center for Clinical Research, an AMR Company	New Orleans	Louisiana
United States	Amicis Reserch Center	Northridge	California
United States	Elixia at Florida Kidney Physicians	Temple Terrace	Florida
United States	Elixia At Clincal Renal Associates	Upland	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
DiaMedica Therapeutics Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events	Incidence, severity, and causality of adverse events	12 weeks
Primary	Change in renal function	eGFR	12 weeks
Primary	Change in urine albumin to creatinine ratio	UACR change from baseline	12 weeks
Primary	Plasma measurements of DM199	Maximum plasma concentration of DM199	12 weeks
Secondary	Tumor necrosis factor receptor 1 (TNF R1) concentration in plasma, change from baseline	TNF R1 change from baseline	12 weeks
Secondary	C-reactive protein (CRP) concentration in plasma, change from baseline	CRP change from baseline	12 weeks
Secondary	Matrix metalloproteainase-9 (MMP-9) concentration in plasma, change from baseline	MMP-9 change from baseline	12 weeks
Secondary	Vascular endothelial growth factor (VEGF) concentration in plasma, change from baseline	VEGF change from baseline	12 weeks
Secondary	Cystatin C concentration in plasma, change from baseline	Cystatin C change from baseline	12 weeks
Secondary	Prostaglandin E2 concentration in plasma, change from baseline	Prostaglandin E2 change from baseline	12 weeks
Secondary	Prostacyclin concentration in plasma, change from baseline	Prostacyclin change from baseline	12 weeks