Phase 3 Clinical Trial With Dapagliflozin in Chronic Kidney Disease in Adolescents and Young Adult Patients

Study Overview
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Brief Summary
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Recent trials have demonstrated positive renal outcomes of sodium-glucose co-transporter-2 inhibitors (SGLT2i) additive to angiotensin-converting-enzyme inhibitors (ACEis) in adult patients with diabetic and non-diabetic chronic kidney disease (CKD). These trials included no children. The hypothesis of DOUBLE PRO-TECT Alport is to demonstrate superiority of the SGLT2i dapagliflozin in preventing progression of the chronic kidney disease Alport syndrome in children and young adults at early stages of disease. Preventing the rise of albuminuria by dapagliflozin would result in a very significant delay of end-stage kidney failure (ESKF) and improved quality of life. If successful, DOUBLE PRO-TECT Alport will change the treatment recommendations for children with CKD, who have a very high unmet medical need.

Official Title
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DOUBLE PRO-TECT Alport: A Confirmatory, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess the Effect of Dapagliflozin on the Progression of Chronic Kidney Disease in Adolescents and Young Adult Patients With Alport Syndrome

Conditions
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Chronic Kidney Failure in Children and Young Adults

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Early stages of CKD with established diagnosis of Alport syndrome at visit 1 (screening) adolescents ≥ 10 to < 18 years with albuminuria (UACR ≥ 300mg/g creatinine) AND eGFR ≥ 30 ml/min/1.73 m2 OR adults ≥ 18 to < 40 years with albuminuria (UACR ≥ 500mg/g creatinine) AND eGFR ≥ 60 ml/min/1.73 m2 Molecular-genetic diagnosis or diagnosis established by kidney biopsy Stable RAS blockade as background therapy. Signed and dated written informed consent. Key exclusion criteria: Medical history that might limit the individual's ability to take trial treatments. Treatment with any SGLT2 inhibitor or within 4 weeks prior to Visit 1. eGFR<60 mL/min/1.73 m2 (CKD-EPI) or requiring dialysis or after kidney-transplantation Uncontrolled arterial hypertension (blood pressure above 145/95 mmHg). Known hypersensitivity or allergy to the investigational products. Any previous or current alcohol or drug abuse. Participation in another trial with an investigational drug ongoing. Women, who are nursing or pregnant, or who are not practicing an acceptable method of birth control.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental intervention: Dapagliflozin (standard dose 10 mg p.o. once daily). Control intervention: Placebo therapy.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Dapagliflozin (standard dose 10 mg p.o. once daily). | Drug: Dapagliflozin<br>* Dapagliflozin (standard dose 10 mg p.o. once daily)<br>|
| Placebo Comparator: Placebo<br>Placebo therapy. | Drug: Placebo<br>* Placebo (standard dose p.o. once daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint | Change from baseline urine albumin to creatinine ratio (UACR) after 48 weeks | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary efficacy endpoint | Change from baseline estimated glomerular filtration rate (eGFR) after 52 weeks (4 weeks off treatment) | 52 weeks | 
| Key secondary safety endpoint | Adverse events (including serious adverse events) | 52 weeks | 
| Adverse events (AE) of special interest | (a) Ketoacidosis or symptomatic hypoglycemic event. | 52 weeks | 
| Adverse events (AE) of special interest | (b) Hyperkalemia (potassium levels ≥15% of the upper normal limit) | 52 weeks | 
| Adverse events (AE) of special interest | (c) Decline in eGFR of ≥ 30% relative from baseline eGFR. | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease in children, pediatric population, nephroprotective therapy in children, Alport syndrome, type IV collagen disease