Clinical Trials Register

Summary
EudraCT Number:	2016-000838-21
Sponsor's Protocol Code Number:	AKB-6548-CI-0016
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-02-07
Trial results	View 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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-000838-21

A.3

Full title of the trial

Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction of Anemia in Subjects with Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE-CORRECTION)

Studio di Fase 3, randomizzato, in aperto, con controllo attivo volto a valutare l'efficacia e la sicurezza di vadadustat somministrato per via orale per la correzione dell'anemia nei soggetti con malattia renale cronica dipendente da dialisi incidente (Dialysis-Dependent Chronic Kidney Disease, DD-CKD) (INNO2VATE-CORRECTION)

A.3.1

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

Efficacy and Safety study to evaluate vadadustat in the correction of anemia in subjects with dialysis-dependent chronic kidney disease (DD-CKD)

Studio a valutare l'efficacia e la sicurezza di vadadustat per la correzione dell'anemia nei soggetti con malattia renale cronica dipendente da dialisi incidente

A.3.2

Name or abbreviated title of the trial where available

INNO2VATE-CORRECTION

A.4.1

Sponsor's protocol code number

AKB-6548-CI-0016

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	AKEBIA THERAPEUTICS, INC.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Akebia Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Quintiles Transnational Corp.
B.5.2	Functional name of contact point	Project Lead
B.5.3	Address:
B.5.3.1	Street Address	Strandbodgatan 1
B.5.3.2	Town/ city	Uppsala
B.5.3.3	Post code	SE-751 45
B.5.3.4	Country	Sweden
B.5.4	Telephone number	0046184311155
B.5.5	Fax number	0046184311430
B.5.6	E-mail	bodil.svanberg@quintiles.com

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	Vadadustat
D.3.2	Product code	AKB-6548
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1000025-07-9
D.3.9.2	Current sponsor code	AKB-6548
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Aranesp
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DARBEPOETINA ALFA
D.3.9.1	CAS number	11096-26-7
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	DARBEPOETINA ALFA
D.3.9.4	EV Substance Code	SUB12486MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Aranesp
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DARBEPOETINA ALFA
D.3.9.1	CAS number	11096-26-7
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	DARBEPOETINA ALFA
D.3.9.4	EV Substance Code	SUB12486MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Anemia in Subjects with Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD)

Anemia nei soggeti con malattia renale cronica dipendente da dialisi incidente

E.1.1.1

Medical condition in easily understood language

Decrease of hemoglobin in the blood of patients suffering from end-stage kidney disease who require dialysis

Diminuzione di emoglobina nel sangue di pazienti affetti da malattia renale allo stadio terminale che necessitano di dialisi

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10076412
E.1.2	Term	Chronic kidney disease stage 5
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Demonstrate the efficacy and safety of vadadustat compared with darbepoetin alfa for the correction and maintenance of HGB in subjects with anemia secondary to CKD who have recently initiated dialysis treatment for end-stage renal disease.

Dimostrare l’efficacia e la sicurezza di vadadustat rispetto a darbepoetina per la correzione e il mantenimento dell’HGB in soggetti con anemia secondaria alla malattia renale cronica (chronic kidney disease, CKD) che hanno recentemente iniziato un trattamento con dialisi per malattia renale terminale.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. ≥ 18 years of age
2. Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease within 16 weeks prior to Screening
3. Mean Screening hemoglobin < 10.0 g/dL

1. Età ≥18 anni
2. Dialisi cronica di mantenimento (peritoneale o emodialisi) per la malattia renale terminale entro 16 settimane prima dello screening.
3. HGB media allo screening <10,0 g/dl

E.4

Principal exclusion criteria

1. Received more than 1 dose of long-acting (e.g., darbepoetin alfa, methoxy polyethylene glycol-epoetin beta [Mircera, C.E.R.A.]) or 2 doses
of short acting eryhropoiesis-stimulating agent (ESA) (e.g., recombinant human erythropoietin [rHuEPO]) within 8 weeks prior to Screening.
Subjects may not receive any ESA during the Screening period.
2. Uncontrolled hypertension
3. Severe heart failure at or during screening (New York Heart Association)
4. Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), urgent coronary revascularisation, hospitalization for Congestive Heart Failure, or stroke within 12 weeks prior to screening
5. Hypersensitivity to darbepoetin or vadadustat, or to any of their excipients

1. Assunzione di più di 1 dose di ESA a lunga durata d’azione (ad es. darbepoetina alfa, metossi polietilene glicole-epoetina beta [Mircera, C.E.R.A]) o 2 dosi di ESA a breve durata d’azione (ad es. eritropoietina umana ricombinante [recombinant human erythropoietin, rHuEPO]) entro 8 settimane prima dello screening. I soggetti non possono ricevere ESA durante il periodo di screening.
2. Ipertensione incontrollata
3. Grave insufficienza cardiaca allo screening o durante lo screening stesso (classe IV della New York Heart Association)
4. Sindrome coronarica acuta (ricovero per angina instabile, infarto miocardico); intervento chirurgico o percutaneo per malattia coronarica, cerebrovascolare o arteriopatia periferica (aortica o delle estremità inferiori); sostituzione o riparazione valvolare chirurgica o percutanea; tachicardia ventricolare prolungata; ricovero per CHF; o ictus entro 12 settimane prima dello screening o durante lo screening stesso.
5. Ipersensibilità a vadadustat, darbepoetina alfa o qualsiasi loro eccipiente.

E.5 End points

E.5.1

Primary end point(s)

1. Mean change in HGB between Baseline and the primary evaluation period
2. Major adverse cardiovascular events (MACE), defined as all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke

1. Variazione media dell’HGB tra il basale e il periodo della valutazione primaria
2. MACE, definito come mortalità per tutte le cause, infarto del miocardio non fatale o ictus non fatale.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Baseline visit, week 36
2. From Baseline visit to end of study

E.5.2

Secondary end point(s)

Efficacy
1. Mean change in hemoglobin value between Baseline and the secondary evaluation period
2. Proportion of subjects with mean HGB within the target range during the primary evaluation period

Safety
3. AEs and SAEs

Efficacia
1. Variazione media dell’HGB tra il basale e il periodo della valutazione secondaria
2. Percentuale di soggetti con HGB media entro l’intervallo target durante il periodo della valutazione primaria

Sicurezza
3. Eventi avversi (EA) ed eventi avversi seri (serious adverse event, SAE).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Baseline visit, Week 52
2. Baseline visit, Week 36
3. From Baseline visit to end of study

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Darbepoetin alfa

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Brazil

Mexico

Russian Federation

Ukraine

United States

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

Ultima visita dell'utimo paziente

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

284

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

116

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

408

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, normal treatment

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

2017-02-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-11-03

P. End of Trial
P.	End of Trial Status	Completed

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