Clinical trial NCT05944016: Phase 3 Clinical Trial with Dapagliflozin in Chronic Kidney Disease in Adolescents and Young Adult Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Kidney Failure in Children and Young Adults
Keywords: chronic kidney disease in children
pediatric population
nephroprotective therapy in children
Alport syndrome
type IV collagen disease
Lead sponsor: University Hospital Goettingen
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2023-07-13
Enrollment: 102
Sex: ALL
Minimum age (years): 10
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental intervention: Dapagliflozin (standard dose 10 mg p.o. once daily). Control intervention: Placebo therapy.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Primary endpoint
timeFrame: 48 weeks
Secondary outcomes:
measure: Key secondary efficacy endpoint
timeFrame: 52 weeks
measure: Key secondary safety endpoint
timeFrame: 52 weeks
measure: Adverse events (AE) of special interest
timeFrame: 52 weeks
measure: Adverse events (AE) of special interest
timeFrame: 52 weeks
measure: Adverse events (AE) of special interest
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg - Children
state: Baden-Württenberg
city: München
country: Germany
facility: LMU Klinikum
state: Bayern
city: München
country: Germany
facility: v. Haunersches Kinderhospital
state: Bayern
city: Frankfurt
country: Germany
facility: Clementine Kinderhospital
state: Hessen
city: Göttingen
country: Germany
facility: University Medicine Goettingen - Adults
state: Lower Saxony
city: Göttingen
country: Germany
facility: University Medicine Goettingen - Childrens Hospital
state: Lower Saxony
city: Köln
country: Germany
facility: Universitätsklinik Köln - Adults
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Universitätsklinik Köln - Children
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitätsklinik Münster - Adults
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Children
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universitätsklinik Leipzig - Children
state: Sachsen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig - Adults
state: Sachsen
city: Berlin
country: Germany
facility: Charite Berlin - Adults
city: Berlin
country: Germany
facility: Charite Berlin - Children
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf - Adults
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf - Children
Study officials:
affiliation: University Medicine Goettingen, Germany
name: Oliver Gross, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gross O, Boeckhaus J, Weber LT, Heerspink HJL, Simon JF, Ahmed R, Gerst C, Duerr U, Walker F, Tostmann R, Helm J, Asendorf T, Friede T; study group of the German Society of Pediatric Nephrology. Protocol and rationale for a randomized controlled SGLT2 inhibitor trial in paediatric and young adult populations with chronic kidney disease: DOUBLE PRO-TECT Alport. Nephrol Dial Transplant. 2025 Apr 1;40(4):679-687. doi: 10.1093/ndt/gfae180.
citation: Gross O, Haffner D, Schaefer F, Weber LT. SGLT2 inhibitors: approved for adults and cats but not for children with CKD. Nephrol Dial Transplant. 2024 May 31;39(6):907-909. doi: 10.1093/ndt/gfae029. No abstract available.