Dose-Ranging Safety, Tolerability, and Efficacy Study of AZD2373 in Participants With APOL1-Mediated Kidney Disease
Purpose
The purpose of this study is to assess the efficacy and safety of AZD2373 in participants diagnosed with APOL1-Mediated Kidney Disease (AMKD) who are homozygotes or compound heterozygotes for APOL1 high-risk genotypes (G1 and G2). The primary hypothesis to be evaluated is that AZD2373, compared with placebo, will result in a greater reduction in UACR as assessed by the relative change from Baseline in UACR at Week 30.
Condition
- APOL1-Mediated Kidney Disease
Eligibility
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age: Male and female participants aged 18 to 65 years, inclusive at the time of informed consent. - Participants who have high-risk APOL1 genotype (G1/G1; G1/G2; G2/G2). The screening period can be extended if there are delays related to the shipment, handling, or processing of genotype results. - A geometric mean UACR ≥ 300 mg/g calculated based on the mean of readings taken from 3 FMV urine samples collected on 3 consecutive days. Since the mean will be assessed for eligibility, any of the 3 readings may fall below 300 mg/g. - eGFR ≥ 25 mL/min/1.73m2. - Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Exclusion Criteria
- Participants with diagnosis of Type 1 diabetes mellitus. - Body Mass Index > 45 kg/m2. - SBP > 180 mmHg/DBP > 110 mmHg (measured when the participant is considered to be at steady state, and preferably when they have taken their BP medications that same day). - QTcF > 470 ms. - Acute coronary syndrome/Acute myocardial infraction +/- coronary intervention with Percutaneous coronary intervention or Coronary artery bypass grafting within 6 months. - Transient ischaemic attack/ stroke within 3 months. - High second to third degree AV block or clinically significant sinus node dysfunction untreated with pacemaker. - A history of ventricular arrhythmias requiring treatment. - Participants with Type 2 diabetes mellitus must be excluded if ANY of the following conditions are present: 1. Current or any past use of insulin 2. Screening Haemoglobin A1c > 8.0% 3. Receiving more than one oral anti-hyperglycaemic agent (excluding SGLT inhibitors which can be taken in addition to one other oral anti-hyperglycaemic agent). - Participant on kidney replacement therapy (dialysis or kidney transplant) or any other organ transplant. - History or serologic evidence of autoimmune-mediated glomerular disease including but not limited to: lupus nephritis (positive lupus serology), ANCA associated vasculitis (antineutrophil cytoplasmic antibody), membranous nephropathy (anti-phospholipase A2 receptor antibody or other autoantibody associated with membranous nephropathy), anti-GBM disease (anti-GBM antibody), or IgA nephropathy. - Another underlying cause of kidney disease that is not associated with APOL1, including but not limited to polycystic kidney disease or, congenital anomalies of the kidney and urinary tract. - History of a diagnosed coagulopathy, a major unexplained bleeding event, or other high-risk bleeding diathesis.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants will be randomized at a 1:1:1 ratio to 3 study treatment arms: - Placebo group - AZD2373 - Arm 1 - AZD2373 - Arm 2
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- AZD2373 (study drug) and placebo will be provided in identical Accessorized pre-filled glass syringes. The Interactive Response technology / Randomisation and Trial Supply Management (IRT/RTSM) will provide to the investigator(s) or pharmacists the kit identification number to be allocated to the participant at the dispensing visit. Routines for this will be described in the IRT/RTSM user manual provided to each centre.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Placebo group |
Participants will be randomized at a 1:1:1 ratio to 3 study treatment arms. Participants will receive SC injection of the assigned dose. |
|
|
Experimental AZD2373 - Arm 1 |
Participants will be randomized at a 1:1:1 ratio to 3 study treatment arms. Participants will receive SC injection of the assigned dose. |
|
|
Experimental AZD2373 - Arm 2 |
Participants will be randomized at a 1:1:1 ratio to 3 study treatment arms. Participants will receive SC injection of the assigned dose. |
|
Recruiting Locations
Research Site
Nashville 4644585, Tennessee 4662168 37232
Nashville 4644585, Tennessee 4662168 37232
More Details
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
information.center@astrazeneca.com
Detailed Description
This is a Phase 2b study to assess efficacy and safety of AZD2373 involving 3 study treatment arms where participants and study personnel including study investigators are blinded to the assigned treatment. Participants with 300 mg/g or greater UACR and eGFR ≥ 25mL/min/1.73m2 will be recruited into the study. Participants on kidney replacement therapy (dialysis or kidney transplant) or any other organ transplant will be excluded. All participants will remain in the study on treatment until the last participant has completed 30 weeks of treatment. The treatment duration will be up to minimum of 30 weeks of study treatment. Approximately 96 participants will be randomized to study intervention (approximately 32 participants in each treatment group).