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

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

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.

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

  1. Molecular-genetic diagnosis or diagnosis established by kidney biopsy
  2. Stable RAS blockade as background therapy.
  3. Signed and dated written informed consent.

Key exclusion criteria:

1. Medical history that might limit the individual's ability to take trial treatments.
2. Treatment with any SGLT2 inhibitor or within 4 weeks prior to Visit 1.
3. eGFR<60 mL/min/1.73 m2 (CKD-EPI) or requiring dialysis or after kidney-transplantation
4. Uncontrolled arterial hypertension (blood pressure above 145/95 mmHg).
5. Known hypersensitivity or allergy to the investigational products.
6. Any previous or current alcohol or drug abuse.
7. Participation in another trial with an investigational drug ongoing.
8. Women, who are nursing or pregnant, or who are not practicing an acceptable method of birth control.