European Alport Therapy Registry - European Initiative Towards Delaying Renal Failure in Alport Syndrome: Current and Novel Therapies
Conditions: Alport Syndrome, Hereditary Kidney Disease, Pediatric Kidney Disease, Thin Basement Membrane Disease, Familial Benign Hematuria
Sponsor: University Hospital Goettingen

Clinical Study Protocol: EARLY PRO-TECT Alport XXL 
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1 Study Title:  
European Alport Therapy Registry- 
EARLY PRO-TECT Alport XXL 
 
Protocol Code: 
EARLY PRO-TECT Alport XXL  
 
 
Protocol 
 
 
Version: 1.2    Date: 21.07.2021 
 
 
Sponsor of the Observational Study  
 
Universitätsmedizin Göttingen 
Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts 
 
 
Coordinating Principal Investigator (LKP)  
 
Prof. Dr. med. Oliver Gross 
_______________________________________________________________ 
 
 
- 
Confidential    -  
 
The information contained in this protocol has to be kept strictly confidential. Therefore the 
protocol is only provided to Investigators in confidence for review, to study staff, 
Independent Ethics Committee/Institutional Review Board, regulatory authorities, CROs, 
and to obtain written informed consent from patients/parents/legal guardian. 
 

Clinical Study Protocol: EARLY PRO-TECT Alport XXL 
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2 Approval Signature Page 
 
The following persons accept the content of this protocol and confirm to conduct 
this study in compliance with Good Clinical Practice and applicable regulatory 
requirements. 
 
 
Approved by: 
 
 
 
 
 
 
 
 
Prof. Dr. Oliver Gross 
Coordinating Principal Investigator 
 
 
 
 
 
 
 
Date 
 
The present study protocol was prepared in accordance with the relevant ICH-GCP 
criteria. 

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3 Organisational Structure 
Sponsor 
Universitätsmedizin Göttingen 
Georg-August-Universität Göttingen 
Robert-Koch-Str. 40 
37075 Göttingen   
 
Coordinating Principal Investigator (LKP) 
Prof. Dr. Oliver Gross 
Klinik für Nephrologie und Rheumatologie 
Universitätsmedizin Göttingen 
Robert-Koch-Str. 40 
37075 Göttingen 
 
Leading Ethics Committee 
Ethikkommission der Universitätsmedizin Göttingen  
Vorsitzender: Prof. Dr. med. Jürgen Brockmöller  
Von-Siebold-Str.3 
37075 Göttingen 
 
Medical Statistics 
Prof. Dr. Tim Friede 
Abt. Medizinische Statistik 
Universitätsmedizin Göttingen 
Humboldtallee 32 
37073 Göttingen   
 
Steering Committee 
Göttingen:  
Prof. Dr. O. Gross, Prof. Dr. Tim Friede  
 
For the Gesellschaft für Pädiatrische Nephrologie (GPN-supported trial):  
 
Essen:  
Prof. Dr. Peter F. Hoyer 
Köln:   
Prof. Dr. Lutz Weber 
Münster: 
Prof. Dr. Martin Konrad 
Hannover: 
Prof. Dr. Lars Pape 
 
Clinical Project Management / Trial Office 
Prof. Dr. Oliver Gross 
Klinik für Nephrologie und Rheumatologie 
Universitätsmedizin Göttingen (UMG) 
Robert-Koch-Str. 40 
37075 Göttingen 
Tel.: +49 (0) 551 39 62236 
Fax: +49 (0) 551 39 65977 
gross.oliver@med.uni-goettingen.de 
 
Trial Project Management 
Universitätsmedizin Göttingen 
Ressort Forschung und Lehre 

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Studienzentrum UMG 
Von-Bar-Str. 2/4 
37075 Göttingen 
Tel.: +49 (0) 551 39 60812 
Fax: +49 (0) 551 39 60846 
E-Mail: studienzentrum-umg@med.uni-goettingen.de  
 
 
Trial Sites: 
A list of Trial Sites participating in this trial is on file at the Trial Office, 
Universitätsmedizin Göttingen (UMG) 
 
Emergency Contact 
Prof. Dr. Oliver Gross 
Klinik für Nephrologie und Rheumatologie 
Universitätsmedizin Göttingen 
Robert-Koch-Str. 40 
37075 Göttingen 
Tel. (office): +49 (0) 551 39 60400 
Fax (office): +49 (0) 551 39 60362 
E-Mail: gross.oliver@med.uni-goettingen.de 
 
Private address:  
Prof. Dr. Oliver Gross 
 
 
 
 
Tel. 
 
 
 
 
 
 
 
 

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4 Table of Contents 
 
1 
Study Title: European Alport Therapy Registry- 
 
EARLY PRO-TECT Alport XXL ................................................................................ 1 
2 
Approval Signature Page ......................................................................................... 2 
3 
Organisational Structure .......................................................................................... 3 
4 
Table of Contents ..................................................................................................... 5 
5 
Synopsis .................................................................................................................. 6 

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5 Synopsis 
 
Study Title 
European Alport Therapy Registry-  
EARLY PRO-TECT Alport XXL  
Type of Project 
Non-interventional, observational prospective (and in 
parts retrospective) study in oligosymptomatic children 
with Alport syndrome  
 
Sponsor  
Georg-August-Universität Göttingen 
Stiftung Öffentlichen Rechts 
Universitätsmedizin Göttingen 
Vorstand 
Robert-Koch-Str. 42 
37075 Göttingen   
Tel.: +49 (0) 551 39-61001 
Fax: +49 (0) 551 39-61002 
 
Coordinating Principal 
Investigator 
Prof. Dr. Oliver Gross 
Klinik für Nephrologie und Rheumatologie 
Universitätsmedizin Göttingen 
Robert-Koch-Str. 40 
37075 Göttingen 
Tel.: +49 (0) 551 39-65309  
Fax: +49 (0) 551 39-65977 
Email: gross.oliver@med.uni-goettingen.de 
 
Deputy for Coordinating 
Principal Investigator 
Jan Böckhaus 
Klinik für Nephrologie und Rheumatologie 
Universitätsmedizin Göttingen 
Robert-Koch-Str. 40 
37075 Göttingen 
Tel.: +49 (0) 551 39 65309 
Fax: +49 (0) 551 39 65977 
Email: jan.boeckhaus@med.uni-goettingen.de 
 
(Sub-) Investigators 
A list of sub-investigators participating in this study is 
kept at the Trial Office (UMG, Göttingen) 
 
Participating Trial Sites 
A list of investigators and trial sites participating in this 
study are kept on file at the Trial Office (UMG, 
Göttingen). 
 
Hypothesis 
 
Treatment of Alport syndrome with Renin–angiotensin–
aldosterone system inhibition from early stages of 
disease is safe and slows disease progression. 
Rationale 
The type IV collagen disease Alport syndrome is the 
second most common monogenic cause of end-stage 
renal failure. Children with Alport syndrome develop renal 
failure early in life. Renin–angiotensin–aldosterone 
system (RAAS) inhibition is the first-line off-label therapy 

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for proteinuric children with Alport syndrome and can 
delay renal failure in a time dependent manner.  
The EARLY PRO-TECT Alport trial was the first 
randomized and placebo-controlled trial to evaluate 
safety and efficacy of RAAS-inhibition in children with 
Alport syndrome. The trial indicated safety and efficacy of 
nephroprotective therapy without statistical significance.  
Aim of this planned study is to analyse renal outcome and 
adverse effects in the longterm observation of all children 
of the trial to further increase quality of the original trial 
results. 
Adult patients with Alport syndrome suffer from 
progressive 
sensorineural 
hearing 
loss 
and 
eye 
abnormalities are often found. The development and 
characteristics of hearing loss and the prevalence of 
ocular findings in children with Alport syndrome need to 
be further analyzed. This study also aims to further 
characterize hearing loss and ocular findings in AS. 
Study Medication 
Non-interventional observational trial 
Placebo 
Non-interventional observational trial 
Study Design 
Strictly observational, non-interventional data acquisition 
with prospective (and in parts retrospective) data analysis 

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Pseudonymized follow-up of the 66 children from the 
EARLY PRO-TECT Alport trial (with the exception of 
drop-out patients) as well as inclusion and follow-up of 
children with Alport syndrome in disease stages 0,I,II (i.e. 
comparable to the patient group of the EARLY PRO-
TECT Alport trial) from South Korea, USA, Canada, 
China, France, England, Spain and Germany 
Alport Syndrome disease stages are defined as: 
0 
 Microhaematuria without microalbuminuria 
I  
 Microalbuminuria (30-300 mg albumin/gCrea) 
II 
 Proteinuria >300 mg albumin/gCrea 
III  
>25% decline of normal creatinine clearance
IV 
End stage renal failure (ESRF)
Information on kidney function of the children will be 
collected as available from existing routine records. 
Adverse events (hyperkalemia, cough, hypotension, 
ANV, malignancy, death) will be monitored. 
Pseudonymized additional data regarding hearing 
function, ocular findings and genetic results will be 
obtained by medical reports as available. 
Timetable 
Date of study / recruitment Start     May 2021 
Date of termination of recruitment  May 2022 
Date of study termination                May 2024 
Total Number of Patients 
Total: 
90-250
Study population 
Oligosymptomatic children and young adults with Alport 
syndrome in early disease stages  
Inclusion Criteria 
1. Definitive diagnosis of Alport syndrome by kidney
biopsy (patient or affected relative/s), and/or
genetic analysis
2. Alport syndrome stages 0, I or II at baseline, if
the patient did not participate in EARLY PRO-
TECT ALPORT trial
3. Patient expresses willingness to participate in
observational study
Exclusion Criteria 
1. uncertain Alport diagnosis
2. Alport syndrome stages III or IV at baseline, if the
patient did not participated in EARLY PRO-TECT
ALPORT trial
3.
Patient expresses unwillingness to participate in
observational study

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Documentation Schedule 
Baseline document (at baseline) and follow up document 
(at every consultation)  
Study Objectives 
Study Objectives: 
Aim of this planned study is to analyse renal outcome and 
adverse 
events 
in 
the 
longterm 
observation 
of 
oligosymptomatic children with Alport syndrome, who 
participated in the EARLY PRO-TECT ALPORT trial. 
Treated and untreated children in similar disease stages 
will be included from South Korea, Germany, UK, France, 
Spain, USA, Canada and China to further increase 
evidence and to enable a comparison between treated 
and untreated children. 
Study Endpoints:  
Primary Endpoint: time to progress of Alport Syndrome 
to the next disease stage under treatment 
Stage 0 to I : Albuminuria >30 mg albumin/gCrea in 
combination with a 3-fold increase from baseline in 
albuminuria 
Stage I to II: Albuminuria >300 mg albumin/gCrea or 
two-fold increase from baseline albuminuria 
Stage II to III: Two-fold increase from baseline 
albuminuria 
Secondary Endpoint: 
Time to progress of Alport Syndrome to the next disease 
stage under treatment compared to children without 
treatment 
Further exploratory endpoints will be assessed during 
this study if data warrant and include, e.g., percentage of 
patients with disease progression.   
For future evaluation for upcoming new therapies or for 
earlier diagnosis or for therapeutic response to therapy 
bio-material (urine and serum) of individual patients will 
be stored at the University Medical Center in Goettingen. 
Safety 
Safety is assessed by recording of adverse events and 
laboratory parameters. 
Data-Safety 
All data will be collected in pseudomized form at the trial 
site in Goettingen. All electronic data will be stored on 
the internal server of the University Medical Center 
Goettingen (intranet). Only the local team of the principal 
investigator will have access to the data with their 

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individual personal account (access to be granted by the 
principal investigator). 
Statistical Analysis 
Statistical analysis of this study will be the responsibility 
of the Dept. Medical Statistics, Universitätsmedizin 
Göttingen, Georg-August-Universität.  
The primary endpoint ‘time to progress of Alport 
syndrome will be assessed. If indicated, additional 
potentially confounding variables such as age will be 
added to the model. 
Pharmacological-toxicological 
Evaluation 
Not applicable 
Risks, Adverse Drug 
Reactions, Drug Interactions, 
Restrictions, 
Contraindications, 
Procedures in Case of 
Emergency 
Not applicable 
Risk-benefit Analysis 
Not applicable