Alkaline Phosphatase as treatment of Ischemia Reperfusion Injury to prevent delayed graft function or APhIRI II

2024-515480-66-01 Therapeutic exploratory (Phase II) Ongoing, recruiting

Start 22 May 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 2 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruiting
Participants planned 1
Countries 1
Sites 2

End stage kidney disease - Kidney transplantation donors receiving kidneys from donation after circulatory death (DCD).

To study whether exogenous alkaline phosphatase can prevent ischemia reperfusion injury in deceased donor kidney transplantation and will thereby decrease the duration of delayed graft function (DGF). DGF is defined as the need for dialysis that started within 7 days post-transplant, excluding single sessions for hyper…

Key facts

Sponsor
Stichting Amsterdam UMC
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Immune System Diseases [C20]
Trial duration
22 May 2023 → ongoing
Decision date (initial)
2024-11-04
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Health Holland B.V. and Alloksys Life Sciences

External identifiers

EU CT number
2024-515480-66-01
EudraCT number
2021-006767-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To study whether exogenous alkaline phosphatase can prevent ischemia reperfusion
injury in deceased donor kidney transplantation and will thereby decrease the duration of
delayed graft function (DGF). DGF is defined as the need for dialysis that started within 7
days post-transplant, excluding single sessions for hyperkalemia.

Secondary objectives 12

  1. Decrease mean duration of hospitalization after kidney transplantation
  2. Decrease of incidence of persistent dialysis DGF (> 14 days)
  3. Decrease incidence of functional DGF and dialysis DGF
  4. Decrease duration of DGF using functional and dialysis definition and a combination of the two
  5. Improve fall of serum creatinine in the first week after transplantation
  6. Improve kidney perfusion contrast renography at day 6
  7. Improve creatinine clearance at 3 months and 1 year after transplantation
  8. Decrease proteinuria at 3 months and 1 year after transplantation
  9. Improve estimated renal glomerular filtration rate (eGFR) calculated with MDRD and the CKD-epi formula at 3 months and 1 year after transplantation
  10. Reduce primary non-function (defined as dialysis dependency or creatinine clearance <20ml/min at 3 months)
  11. Reduce incidence of biopsy proven rejection within one year follow-up period
  12. Improve all-cause mortality at day 28 and 90 and 1 year

Conditions and MedDRA coding

End stage kidney disease - Kidney transplantation donors receiving kidneys from donation after circulatory death (DCD).

Regulatory references

Plan to share IPD
Yes
IPD plan description
Coded data will also be made available to a third party; Alloksys life sciences B.V. Only relevant patient baseline criteria and information related to the outcomes specified in this protocol will be provided to this third party. Personal data such as birth year will not be made available.
EU CT numberTitleSponsor
2024-515480-66-00 Alkaline Phosphatase as treatment of Ischemia Reperfusion Injury to prevent delayed graft function Stichting Amsterdam UMC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. Patients recipients of a donor awaiting cardiac death on the intensive care (definition of a donor cardiac death type III according to the ‘Maastricht classification’)
  2. Age >18
  3. Can give written informed consent

Exclusion criteria 3

  1. Strict vegetarians
  2. Vegans
  3. History of allergy to bovine proteins

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Difference between treatment and placebo group in delayed graft function (DGF) duration (in days) as measured on day 28. DGF is defined as need for dialysis within 7 days after transplantation, excluding single sessions for hyperkalemia. No need for dialysis will be registered as 0 days.

Secondary endpoints 12

  1. Mean duration of hospitalization after kidney transplantation
  2. Incidence of persistent dialysis DGF (> 14 days)
  3. Incidence of functional and dialysis DGF
  4. Duration of DGF using functional and dialysis definition and a combination of the two
  5. Dall of serum creatinine in the first week after transplantation
  6. Kidney perfusion contrast renography at day 6
  7. Creatinine clearance at 3 months and 1 year after transplantation
  8. Proteinuria at 3 months and 1 year after transplantation
  9. Estimated renal glomerular filtration rate (eGFR) calculated with MDRD and the CKD-epi formula at 3 months and 1 year after transplantation
  10. Primary non-function (defined as dialysis dependency or creatinine clearance <20ml/min at 3 months).
  11. Incidence of biopsy proven rejection within one year follow-up period.
  12. All-cause mortality at day 28 and 90 and 1 year.

Investigational products

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

Test 1

bRESCAP

PRD11579023 · Product

Active substance
Alkaline Phosphatase, Bovine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
IV INFUSION
Max daily dose
50000 IU international unit(s)
Max total dose
75000 IU international unit(s)
Max treatment duration
3 Day(s)
Authorisation status
Not Authorised
MA holder
AMSTERDAM UMC
Paediatric formulation
No
Orphan designation
No

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Amsterdam UMC

Sponsor organisation
Stichting Amsterdam UMC
Address
De Boelelaan 1117
City
Amsterdam
Postcode
1081 HV
Country
Netherlands

Scientific contact point

Organisation
Stichting Amsterdam UMC
Contact name
Liffert Vogt

Public contact point

Organisation
Stichting Amsterdam UMC
Contact name
Debby Roosblad

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ongoing, recruiting 1 2
Rest of world 0

Investigational sites

Netherlands

2 sites · Ongoing, recruiting
Leiden University Medical Center
nephrology, Albinusdreef 2, 2333 ZA, Leiden
Amsterdam UMC Stichting
Internal medicine, Meibergdreef 9, 1105 AZ, Amsterdam

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2023-05-22 2023-05-22

Results and documents

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

Documents 9 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-515480-66-01 CLEAN 5
Recruitment arrangements (for publication) K1_Recruitment arrangements 2
Recruitment arrangements (for publication) K1_Recruitment arrangements TC 2
Subject information and informed consent form (for publication) L1_SIS and ICF description AMC CLEAN 2.3
Subject information and informed consent form (for publication) L1_SIS and ICF description AMC TC 2.3
Subject information and informed consent form (for publication) L1_SIS and ICF description CLEAN 2.2
Subject information and informed consent form (for publication) L1_SIS and ICF description LUMC 1
Synopsis of the protocol (for publication) D1_Protocol synopsis NL 2024-515480-66-01 Dutch 1
Synopsis of the protocol (for publication) D1_Protocol synopsis NL 2024-515480-66-01 english 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-09 Netherlands Acceptable
2024-11-04
2024-11-04
2 SUBSTANTIAL MODIFICATION SM-1 2025-05-08 Netherlands Acceptable
2025-06-13
2025-06-13
3 SUBSTANTIAL MODIFICATION SM-4 2025-09-11 Netherlands Acceptable 2025-10-07