Clinical Trials Register

Summary
EudraCT Number:	2021-002505-10
Sponsor's Protocol Code Number:	NL77754.018.21
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-11-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2021-002505-10

A.3

Full title of the trial

Rescue Alkaline Phosphatase In Defense against all cause Acute Kidney Injury (RAPID-AKI)

Rescue alkalisch fosfatase als behandeling van acute nierinsufficiëntie onafhankelijk van oorzaak (RAPID-AKI)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Rescue alkaline posphatase as a treatment for acute kidney injury

Rescue alkalisch fosfatase als behandeling van acute nierschade

A.3.2

Name or abbreviated title of the trial where available

RAPID

A.4.1

Sponsor's protocol code number

NL77754.018.21

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Amsterdam University Medical Centre
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Health Holland
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Alloksys Life Sciences
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Amsterdam University Medical Centre
B.5.2	Functional name of contact point	Secretariat dept. of nephrology
B.5.3	Address:
B.5.3.1	Street Address	Meibergdreef 9
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1105AZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31020566 5990
B.5.6	E-mail	secr.nefrologie@amsterdamumc.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	bovine alkaline phosphatase
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bovine alkaline phosphatase
D.3.9.3	Other descriptive name	BOVINE INTESTINAL ALKALINE PHOSPHATASE
D.3.9.4	EV Substance Code	SUB27380
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute kidney injury

Acute nierschade

E.1.1.1

Medical condition in easily understood language

Acute kidney injury

Acute nierschade

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10069339
E.1.2	Term	Acute kidney injury
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10080269
E.1.2	Term	Stage 2 acute kidney injury
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10080271
E.1.2	Term	Stage 3 acute kidney injury
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To decrease the time and extent of acute injury to the kidney to prevent kidney disease and death. Thus, AKI patients treated with AP have a lower incidence of the composite endpoint of acute kidney disease on day 28 and mortality at 90 days as opposed to patients treated with placebo. And to prove safety of study medication for use in AKI patients.

Om de tijd en de omvang van acuut letsel aan de nier te verminderen om nierziekte en overlijden te voorkomen. AKI-patiënten die met AP worden behandeld, hebben dus een lagere incidentie van het samengestelde eindpunt van "acute kidney disease" op dag 28 en mortaliteit tot en met 90 dagen in tegenstelling tot patiënten die met placebo werden behandeld. En om veiligheid van studiemedicatie aan te tonen in deze patiëntengroep.

E.2.2

Secondary objectives of the trial

1. Faster decline of biomarkers indicating kidney injury from day 0 to day 3 (T-0h and T-72h)
2. Faster decline of albuminuria measured on day 0-7, and lower incidence of albuminuria on day 28, 90 and at one year
3. Better renal function at 3 months as measured by gold standard GFR
4. Lower incidence of AKD and 90-day mortality
5. Lower creatinine level and higher estimated GFR (CKD-epi) at 28 and 90 days and 1 year
6. Shorter duration (in days) of AKI
7. Lower need and shorter duration of renal replacement therapy in hospital, and at 1 year.

Outcomes in subgroup of AUMC patients
1. Overall better renal function, plasma flow, and renal functional reserve as measured with isotopic iothalamate- and hippuric acid clearance

Macrovascular outcomes; the intervention group (AP infusion) has –when compared to placebo group- overall:
1. Lower all-cause in hospital mortality and at one year
2. Fewer cardiovascular events within 1 year after AKI

1. Snellere afname van biomarkers die wijzen op nierbeschadiging van dag 0 tot dag 3 (T-0h en T-72h)
2. Snellere afname van albuminurie gemeten op dag 0-7, en lagere incidentie van albuminurie op dag 28, 90 en na één jaar
3. Betere nierfunctie na 3 maanden, gemeten met gouden standaard GFR
4. Lagere incidentie van AKD en 90-dagen mortaliteit
5. Lagere creatininespiegel en hogere geschatte GFR (CKD-epi) na 28 en 90 dagen en 1 jaar
6. Kortere duur (in dagen) van AKI
7. Lagere noodzaak en kortere duur van nierfunctievervangende therapie tijdens ziekenhuisopname en na 1 jaar.

Resultaten in subgroep van AUMC-patiënten
1. over het algemeen een betere nierfunctie, plasmastroom en nierfunctiereserve, gemeten met isotopische iothalamaat- en hippuurzuurklaring

Macrovasculaire uitkomsten;
1. Lagere sterfte door alle oorzaken in het ziekenhuis en na één jaar
2. Minder cardiovasculaire voorvallen binnen 1 jaar na AKI

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Diagnosed with AKI Stage 2 or 3
• Age 18 years and older
• Written informed consent by patient or representative

• Gediagnosticeerd met AKI stadium 2 of 3
• Leeftijd 18 jaar en ouder
• Schriftelijke geïnformeerde toestemming van patiënt of vertegenwoordiger

E.4

Principal exclusion criteria

• History of allergy to bovine proteins or strict vegan/vegetarian diet
• Chronic kidney disease with a baseline eGFR < 20ml/min
• History of previous administration of alkaline phosphatase, because of a potential allergic reaction.
• Pregnant or breastfeeding women
• In case of a repeated AKI in one-year follow-up, already included patients are not allowed to receive AP or placebo again.
• Patients undergoing nephrectomy
• Active malignancy or HIV infection
• Patients expected to have rapidly fatal disease within 24 hours
• Pre-existing rapid progressive glomerulonephritis

• voorgeschiedenis van allergie voor runder-eiwit of veganistisch/ strikt vegetarisch dieet
• Chronische nierziekte met een baseline eGFR < 20ml/min
• voorgeschiedenis van eerdere toediening van alkalische fosfatase, vanwege een mogelijke allergische reactie.
• Zwangere vrouwen of vrouwen die borstvoeding geven
• In het geval van een herhaalde AKI in één jaar follow-up, mogen reeds geïncludeerde patiënten niet nog eens AP of placebo krijgen.
• Patiënten die nefrectomie ondergaan
• Actieve maligniteit of HIV-infectie
• Patiënten die naar verwachting binnen 24 uur een snel dodelijke ziekte zullen krijgen
• Reeds bestaande snel progressieve glomerulonefritis

E.5 End points

E.5.1

Primary end point(s)

Composite endpoint of incidence of AKD on day 28 and mortality at day 90.
safety: Any reactions to study medication of administration of exogenous AP in the context of AKI (infusion related reactions and side-effects)

Samengesteld eindpunt van incidentie van AKD op dag 28 en mortaliteit op dag 90.
Veiligheid: Eventuele reacties op studiemedicatie of toediening van exogene AP in de context van AKI (infusiegerelateerde reacties en bijwerkingen)

E.5.1.1

Timepoint(s) of evaluation of this end point

28 days (AKD) and 90 days (mortality)

dag 28 (AKD) en 90 (mortaliteit)

E.5.2

Secondary end point(s)

Renal endpoints:
1. Decline of biomarkers indicating kidney injury from day 0 to day 3 (before and after infusion of AP or placebo (T-0h and T-72h))
2. Decline of albuminuria measured on day 0-7 and incidence of albuminuria on day 28 and 90 and at one year
3. Renal function at 3 months as measured by gold standard GFR
4. Separate assessment of proportion of AKD on day 28 and 90-day mortality
5. Serum creatinine level and estimated GFR (CKD-epi) at 28 and 90 days and 1 year after AKI
6. Duration (in days) of AKI
7. Need and duration of renal replacement therapy during hospitalization, and at 1 year.

Subgroup of AUMC patients
1. Renal function, plasma flow, and renal functional reserve as measured with isotopic iothalamate- and hippuric acid clearance

Macrovascular endpoints:
1. All-cause in hospital mortality and at one year
2. Cardiovascular events (myocardial infarction, angina pectoris, transient ischemic accident, cerebral infarction, peripheral arterial vascular disease), within 1 year after AKI

Nier eindpunten:
1. Daling van biomarkers die wijzen op nierbeschadiging van dag 0 tot dag 3 (vóór en na infusie van AP of placebo (T-0h en T-72h))
2. Daling van albuminurie gemeten op dag 0-7 en incidentie van albuminurie op dag 28 en 90 en na één jaar
3. Nierfunctie na 3 maanden zoals gemeten met gouden standaard GFR
4. Afzonderlijke beoordeling van het aandeel AKD op dag 28 en 90 dagen sterfte
5. Serumcreatininespiegel en geschatte GFR (CKD-epi) op 28 en 90 dagen en 1 jaar na AKI
6. Duur (in dagen) van AKI
7. Noodzaak en duur van nierfunctievervangende therapie tijdens ziekenhuisopname en na 1 jaar.

Subgroep van AUMC-patiënten
1. Nierfunctie, plasmastroom en nierfunctiereserve zoals gemeten met isotopische iothalamaat- en hippuurzuurklaring

Macrovasculaire eindpunten:
1. Sterfte door alle oorzaken in ziekenhuis en na één jaar
2. Cardiovasculaire voorvallen (myocardinfarct, angina pectoris, voorbijgaand ischemisch ongeval, herseninfarct, perifeer arterieel vaatlijden), binnen 1 jaar na AKI

E.5.2.1

Timepoint(s) of evaluation of this end point

day 0-7, day 28, day 90 and at one year

dag 0-7, dag 28, dag 90 en op 1 jaar

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

lvls

laatse visite laatste patiënt

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

150

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-11-06.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Intubated and sedated patients on the intensive care unit suffering from acute kidney injury will be included as well

Geïntubeerde en gesedeerde patiënten op de intensieve zorgafdeling met acute nierschade zullen ook geïncludeerd worden.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

300

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard of care

Standaardzorg

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-11-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-07-27

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials