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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Failure in Children and Young Adults
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Oliver Gross, MD; Phone Number: 60488 +4955139; Email: gross.oliver@med.uni-goettingen.de

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Not yet recruiting
    • Charite Berlin - Adults
    • Contact: Jan Halbritter, MD
    • Principal Investigator: Jan Halbritter, MD
    • Sub-Investigator: Mira Choi, MD
    • Sub-Investigator: Markus Schüler, MD
  • Berlin, Germany, 10117
    • Not yet recruiting
    • Charite Berlin - Children
    • Contact: Jutta Gellermann, MD
    • Principal Investigator: Jutta Gellermann, MD
    • Sub-Investigator: Julia Thumfart, MD
  • Hamburg, Germany, 20246
    • Not yet recruiting
    • Universitätsklinikum Hamburg-Eppendorf - Adults
    • Contact: Markus Gödel, MD
    • Principal Investigator: Markus Gödel, MD
    • Sub-Investigator: Tobias B. Huber, MD
    • Sub-Investigator: Florian Grahammer, MD
  • Hamburg, Germany, 20251
    • Not yet recruiting
    • Universitätsklinikum Hamburg-Eppendorf - Children
    • Contact: Jun Oh, MD
    • Principal Investigator: Jun Oh, MD
    • Sub-Investigator: R. Schild, MD
  • Baden-Württenberg
    • Heidelberg, Baden-Württenberg, Germany, 69120
      • Not yet recruiting
      • Universitätsklinikum Heidelberg - Children
      • Contact: Maria Luisa Möller-Winheim
      • Principal Investigator: Burkhard Tönshoff, MD
  • Bayern
    • München, Bayern, Germany, 80336
      • Not yet recruiting
      • LMU Klinikum
      • Contact: Volker Vielhauer, MD
      • Principal Investigator: Volker Vielhauer, MD
      • Sub-Investigator: Hans-Joachim Anders, MD
    • München, Bayern, Germany, 81337
      • Not yet recruiting
      • v. Haunersches Kinderhospital
      • Contact: Bärbel Lange-Sperandio, MD
      • Principal Investigator: Bärbel Lange-Sperandio, MD
      • Sub-Investigator: Klaus Richard, MD
  • Hessen
    • Frankfurt, Hessen, Germany, 60316
      • Not yet recruiting
      • Clementine Kinderhospital
      • Contact: Claudia Kuss, PhD; Email: c.kuss@ckhf.de
      • Principal Investigator: Kay Latta, MD
      • Sub-Investigator: Matthias Hansen, MD
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • Recruiting
      • University Medicine Goettingen - Adults
      • Contact: Carmen Scherf; Email: carmen.scherf@med.uni-goettingen.de
      • Principal Investigator: Oliver Gross, MD
      • Sub-Investigator: Jan Boeckhaus, MD
    • Göttingen, Lower Saxony, Germany, 37075
      • Recruiting
      • University Medicine Goettingen - Childrens Hospital
      • Contact: Carmen Scherf; Email: carmen.scherf@med.uni-goettingen.de
      • Principal Investigator: Matthias Kettwig, MD
      • Sub-Investigator: Marie Hansen, MD
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Not yet recruiting
      • Universitätsklinik Köln - Adults
      • Sub-Investigator: Thomas Benzing, MD
      • Contact: Polina Todorova, MD
      • Principal Investigator: Roman-Ulrich Müller, MD
      • Sub-Investigator: Polina Todorova, MD
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Not yet recruiting
      • Universitätsklinik Köln - Children
      • Sub-Investigator: Stefan Kohl, MD
      • Contact: Stefan Kohl, MD
      • Principal Investigator: Lutz Weber, MD
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Not yet recruiting
      • Universitätsklinik Münster - Adults
      • Contact: Eva Brand, MD
      • Principal Investigator: Hermann-Josef Pavenstädt, MD
      • Sub-Investigator: Eva Brand, MD
    • Münster, Nordrhein-Westfalen, Germany, 48149
      • Not yet recruiting
      • Universitätsklinikum Münster - Children
      • Sub-Investigator: Jens König, MD
      • Contact: Sabine König, MD
      • Principal Investigator: Martin Konrad, MD
      • Sub-Investigator: Sabine König, MD
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Not yet recruiting
      • Universitätsklinik Leipzig - Children
      • Contact: Katalin Dittrich, MD
      • Principal Investigator: Katalin Dittrich, MD
      • Sub-Investigator: Nora Liebmann, MD
    • Leipzig, Sachsen, Germany, 04103
      • Not yet recruiting
      • Universitätsklinikum Leipzig - Adults
      • Contact: Jonathan de Fallois, MD
      • Principal Investigator: Jonathan de Fallois, MD
      • Sub-Investigator: Jan Halbritter, MD
      • Sub-Investigator: Bastian Krüger, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin (standard dose 10 mg p.o. once daily).	Drug: Dapagliflozin; Dapagliflozin (standard dose 10 mg p.o. once daily)
Placebo Comparator: Placebo; Placebo therapy.	Drug: Placebo; Placebo (standard dose p.o. once daily)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Goettingen
• Collaborators: German Research Foundation
• Investigators: Principal Investigator: Oliver Gross, MD, University Medicine Goettingen, Germany

Study record dates

Study Major Dates

• Study Start (Estimated): March 10, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 1, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 13, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: pediatric population; Alport syndrome; chronic kidney disease in children; nephroprotective therapy in children; type IV collagen disease
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: UMG DOUBLE PRO-TECT 2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared after end of study on request and with valid IRB-vote and data protection protocol by applicant.
• IPD Sharing Time Frame: Documents will be shared after end of study on request and with valid IRB-vote and data protection protocol by applicant.
• IPD Sharing Access Criteria: IPD will be shared after end of study on request and with valid IRB-vote and data protection protocol by applicant.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No