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 adolescent and young adult patients with Alport syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsmedizin Goettingen

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

19 Mar 2024 → ongoing

Decision date (initial)

2024-02-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Deutsche Forschungsgemeinschaft

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Recent trials have demonstrated positive renal outcomes of sodium–glucose co-transporter-2 inhibitors (SGLT2i) additive to ACEis in adult patients with diabetic and non-diabetic CKD [6-9]. These trials included less than 10 adult AS patients and no children. Our hypothesis is to demonstrate superiority of the SGLT2i dapagliflozin in preventing progression of AS 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 ESKF and improved quality of life. If successful, DOUBLE PRO-TECT Alport will change the
treatment recommendations for children with AS, who have a very high unmet medical need.

Conditions and MedDRA coding

Alport syndrome

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Early stages of CKD with established diagnosis of Alport syndrome at visit 1 (screening)
2. adolescents ≥ 10 to < 18 years with albuminuria (UACR ≥ 300mg/g Crea) OR adults ≥ 18 to < 40 years with albuminuria (UACR ≥ 500mg/g Crea) AND eGFR ≥ 60 ml/min/1.73 m2
3. Molecular-genetic diagnosis (any type of Alport gene variant) or diagnosis established by kidney biopsy
4. Stable RAS blockade as standard of care background therapy (defined as no adjustment to dose in the last three months prior the baseline visit).
5. Signed and dated written informed consent

Exclusion criteria 10

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. Requiring dialysis or after kidney-transplantation
4. Uncontrolled arterial hypertension (blood pressure >145/95 mmHg)
5. Type 1 diabetes OR type 2 diabetes with previous history of diabetic ketoacidosis
6. Known hypersensitivity or allergy to the investigational product (contains lactulose)
7. Any previous or current alcohol or drug abuse
8. Participation in another trial with an investigational drug ongoing
9. Pre-menopausal women, who are nursing or pregnant, or who are not practicing an acceptable method of birth control
10. Lack of basic understanding of German language (required for patient questionnaires)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to 48 weeks in (log transformed) UACR.

Secondary endpoints 4

1. eGFR change from baseline to Week 52
2. In adults, change from baseline to Week 48 in SF- 36.
3. In adolescents, change from baseline to Week 48 in PedsQL
4. Difference between treatment groups in eGFR change from Week 4 eGFR to Week 48 measurement

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsmedizin Goettingen

Sponsor organisation

Universitaetsmedizin Goettingen

Address

Robert-Koch-Strasse 40, Weende Weende

City

Goettingen

Postcode

37075

Country

Germany

Scientific contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Florian Walker

Public contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Florian Walker

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications