Clinical Trials Register

Summary
EudraCT Number:	2007-004146-32
Sponsor's Protocol Code Number:	AFX01-13
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:	2008-07-03
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

2007-004146-32

A.3

Full title of the trial

AFX01-13: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of AF37702 Injection for the Correction of Anemia in Patients with Chronic Renal Failure (CRF) noton Dialysis and not on Erythropoiesis Stimulating Agent (ESA) Treatment

AFX01-13: studio di fase 3, multicentrico, randomizzato, in aperto, controllato vs farmaco attivo, sull`efficacia e la sicurezza di AF37702 preparazione iniettabile nella correzione dell`anemia in pazienti con insufficienza renale cronica (IRC) non in dialisi e non in trattamento con un agente stimolante l`eritropoiesi (ESA, Erythropoiesis Stimulating Agent)

A.3.2

Name or abbreviated title of the trial where available

PEARL 2

A.4.1

Sponsor's protocol code number

AFX01-13

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	AFFYMAX 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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	NA
D.3.2	Product code	AF37702
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Other antianemic preparations
D.3.9.1	CAS number	913976-27-9
D.3.9.2	Current sponsor code	AF37702
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	10
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	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
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 SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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 injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Darbepoetin alfa
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.3	Concentration number	100
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	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

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 Patients with Chronic Renal Failure not on Dialysis and not on Erythopoiesis Stimulating Agent (ESA) Treatment

Anemia in Pazienti affetti da Malattia Renale Cronica, non in dialisi e non in trattamento con agenti stimolanti l'eritropoiesi (ESA)

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10061101
E.1.2	Term	Deficiency anaemia
E.1.2	System Organ Class	10005329 - Blood and lymphatic system 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 demonstrate the safety and efficacy of AF37702 Injection in the correction of anemia in patients with CRF not on dialysis and not on ESA treatment • To demonstrate the non-inferiority of AF37702 Injection to darbepoetin alfa in increasing Hgb in patients with CRF not on dialysis and not on ESA treatment

• Dimostrare la sicurezza e l`efficacia di AF37702 preparazione iniettabile nella correzione dell`anemia in pazienti con IRC non in dialisi e non in trattamento con ESA • Dimostrare la non inferiorita` di AF37702 preparazione iniettabile rispetto alla darbepoietina alfa nell`incrementare l`Hb in pazienti con IRC non in dialisi e non in trattamento con ESA

E.2.2

Secondary objectives of the trial

Not applicable

Non applicabile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines. 2. Males or females ≥ 18 years of age. 3. Females of child-bearing potential who are sexually active must be willing to practice a highly effective method of birth control for at least 4 weeks prior to randomization, and must be willing to continue contraception until at least 4 weeks after the last dose of study treatment. 4. Chronic Renal Failure with an estimated glomerular filtration rate < 60 mL/min/1.73m2 using the 4-variable Modification of Diet in Renal Disease (MDRD) formula within 4 weeks prior to randomization, and not expected to begin dialysis for at least 12 weeks. 5. Two consecutive Hgb values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization, with ≤ 1.3 g/dL difference between the two values and no less than 5 days apart, with the last value within 10 days prior to randomization. 6. One transferrin saturation (TSAT) ≥ 20% or one ferritin level ≥ 100 ng/mL within 4 weeks prior to randomization. 7. One serum or red cell folate level ≥ lower limit of normal during the 4 weeks prior to randomization. 8. One vitamin B12 level ≥ lower limit of normal during the 4 weeks prior to randomization.

1. Il paziente e` stato informato della natura sperimentale dello studio e ha fornito un consenso informato scritto in conformita` con le linee guida dell`istituzione, locali e nazionali. 2. Soggetti di sesso maschile o femminile di eta` ≥ 18 anni. 3. Le donne in eta` fertile sessualmente attive devono essere disposte a utilizzare un metodo contraccettivo molto efficace per almeno 4 settimane prima della randomizzazione e a proseguire la contraccezione per almeno 4 settimane dopo l`ultima somministrazione del trattamento in studio. 4. Insufficienza renale cronica con una velocita` di filtrazione glomerulare < 60 ml/min/1,73 m2 stimata con la formula della modifica della dieta nella malattia renale (MDRD, Modification of Diet in Renal Disease) a 4 variabili nelle 4 settimane precedenti la randomizzazione e per la quale non si preveda l`inizio della dialisi per almeno 12 settimane. 5. Due valori consecutivi dell`Hb ≥ 8,0 g/dl e < 11,0 g/dl nelle 4 settimane precedenti la randomizzazione, con una differenza ≤ 1,3 g/dl tra i due valori, ad almeno 5 giorni di distanza l`uno dall`altro, con l`ultimo valore nei 10 giorni precedenti la randomizzazione. 6. Una saturazione della transferrina (TSAT) ≥ 20% o un livello di ferritina ≥ 100 ng/ml nelle 4 settimane precedenti la randomizzazione. 7. Un livello del folato nel siero o nei globuli rossi non al di sotto del limite inferiore della norma durante le 4 settimane precedenti la randomizzazione. 8. Un livello della vitamina B12 non al di sotto del limite inferiore della norma durante le 4 settimane precedenti la randomizzazione.

E.4

Principal exclusion criteria

1. Females who are pregnant or breast-feeding. 2. Treatment with an ESA in the 12 weeks prior to randomization. 3. Known intolerance to any ESA, parenteral iron supplementation, or PEGylated molecule. 4. Prior chronic hemodialysis or chronic peritoneal dialysis treatment. (Note: renal transplant patients who are at least 6 months post-transplant and have not had chronic dialysis post-transplant are eligible.) 5. Known bleeding or coagulation disorder. 6. Known hematologic disease or cause of anemia other than renal disease (e.g., pure red cell aplasia (PRCA), homozygous sickle-cell disease, thalassemia, multiple myeloma, hemolytic anemia, myelodysplastic syndrome etc.). 7. Poorly controlled hypertension within 4 weeks prior to randomization, per Investigator's clinical judgment. 8. Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent. 9. Evidence of active malignancy within one year prior to randomization. (Note for the purposes of this protocol, active malignancy does not include: non-melanoma skin cancer, carcinoma in situ that has been completely excised, other cancers for which treatment was completed at least one year ago with no continuing treatment and no evidence of metastasis, and other cancers that were diagnosed and treatment completed more than one year ago and within the past year are without evidence of metastasis and treated only with adjuvant hormonal therapy). 10. A scheduled kidney transplant (Note: patients currently on a transplant wait list are not excluded unless there is an identified donor). 11. Scheduled surgery that may be expected to lead to significant blood loss. 12. RBC or whole blood transfusion within 12 weeks prior to randomization. 13. Previous exposure to any investigational agent within 4 weeks prior to randomization, or planned receipt of an investigational agent, other than as specified by this protocol, during the study period. 14. Previous exposure to AF37702 Injection.

1. Donne in gravidanza o che allattano. 2. Trattamento con un ESA nelle 12 settimane precedenti la randomizzazione. 3. Intolleranza nota a qualunque ESA, all`integrazione di ferro per via parenterale o alle molecole pegilate. 4. Precedente trattamento cronico di emodialisi o dialisi peritoneale.( Nota: sono eleggibili i pazienti che hanno subito un trapianto da almeno 6 mesi e non sono stati sottoposti a dialisi cronica dopo il trapianto.) 5. Sanguinamento o disturbo della coagulazione noti. 6. Malattia ematologica o causa di anemia diversa dalla nefropatia nota (es. aplasia eritroide pura (PRCA, pure red cell aplasia), anemia falciforme omozigote, talassemia, mieloma multiplo, anemia emolitica, sindrome mielodisplastica, ecc.) 7. Ipertensione scarsamente controllata nelle 4 settimane precedenti la randomizzazione, in base al parere clinico dello sperimentatore. 8. Qualunque malattia o disturbo clinicamente significativi che, a giudizio dello sperimentatore, potrebbe interferire con l`aderenza al protocollo o con la capacita` del paziente di fornire il consenso informato. 9. Evidenza di una neoplasia maligna attiva nell`anno precedente la randomizzazione (nota ai fini di questo protocollo, la neoplasia maligna non include: tumori maligni cutanei diversi dal melanoma, carcinomi in situ escissi in modo radicale, altri tumori maligni il cui trattamento e` stato concluso almeno nell' anno precedente, che non siano attualmente trattati e che non diano evidenze di metastasi, e altri tumori maligni diagnosticati e trattati nell'anno precedente solamente con terapia ormonale adiuvante e che nell'anno trascorso non abbiano dato evidenze di metastasi. 10. Trapianto renale programmato (Nota: i pazienti in lista d`attesa per un trapianto non sono esclusi a meno che non sia gia` stato identificato un donatore). 11. Intervento chirurgico programmato che si ritiene potrebbe comportare una significativa perdita ematica. 12. Trasfusione di globuli rossi o di sangue intero nelle 12 settimane precedenti la randomizzazione. 13. Esposizione a qualunque agente sperimentale nelle 4 settimane precedenti la randomizzazione, o assunzione programmata di un agente sperimentale diverso da quello specificato dal presente protocollo, durante lo studio. 14. Precedente esposizione a AF37702 preparazione iniettabile

E.5 End points

E.5.1

Primary end point(s)

Mean change in Hgb between baseline (the mean of the three central laboratory Hgb values collected most recently prior to Dose 1) and the Evaluation Period (mean Hgb from Weeks 25 through 36)

Il cambiamento medio nel valore di emoglobina (Hgb) tra il basale e il Periodo di Valutazione. Il valore basale di emoglobina (Hgb) e` definito come la media di tre valori di emoglobina (Hgb): i due valori piu` recenti di emoglobina (Hgb) rilevati prima del giorno di randomizzazione e il valore ottenuto il giorno della randomizzazione. Il valore medio di emoglobina (Hgb) durante il Periodo di Valutazione per ciascun paziente sara` calcolato come la media dei valori di emoglobina (Hgb) disponibili durante le Settimane 25-36 dello Studio.

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

Yes

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

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

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

Information not present in EudraCT

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
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	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	25
F.4.2	For a multinational trial
F.4.2.1	In the EEA	228
F.4.2.2	In the whole clinical trial	450

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

2008-05-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-03-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-12-21

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