Clinical Trials Register

Summary
EudraCT Number:	2015-003433-10
Sponsor's Protocol Code Number:	GP17-302
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:	2018-02-27
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-003433-10

A.3

Full title of the trial

GP17-302 A randomized, double-blind, parallel-group, multicenter study to demonstrate similar efficacy and to compare safety and immunogenicity of GP2017 and Humira® in patients with moderate to severe active rheumatoid arthritis

GP17-302 Studio randomizzato, in doppio cieco, volto a dimostrare la simile efficacia e sicurezza di GP2017 e Humira® in pazienti affetti da artrite reumatoide in fase attiva da moderata a grave

A.3.1

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

ADMYRA Trial: Clinical trial to compare treatment with GP2017 and Humira® in patients with Rheumatoid Arthritis

Studio ADMYRA: studio clinico per valutare l'efficacia e sicurezza di GP2017 nell’artrite reumatoide

A.3.2

Name or abbreviated title of the trial where available

ADMYRA trial

Studio ADMYRA

A.4.1

Sponsor's protocol code number

GP17-302

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	HEXAL AG
B.1.3.4	Country	Germany
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	Hexal, AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hexal, AG
B.5.2	Functional name of contact point	Biopharmaceuticals Clinical Dev.
B.5.3	Address:
B.5.3.1	Street Address	Industriestrasse 25,
B.5.3.2	Town/ city	Holzkirchen
B.5.3.3	Post code	83607
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049 8024 476 2935
B.5.5	Fax number	0049 8024 476 4880
B.5.6	E-mail	julia.jauch@sandoz.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	Adalimumab
D.3.2	Product code	GP2017
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	GP2017
D.3.9.3	Other descriptive name	ADALIMUMAB
D.3.9.4	EV Substance Code	SUB20016
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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)	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	Yes
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	Humira
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	nd
D.3.9.3	Other descriptive name	ADALIMUMAB
D.3.9.4	EV Substance Code	SUB20016
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Yes
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

rheumatoid arthritis

artrite reumatoide

E.1.1.1

Medical condition in easily understood language

rheumatoid arthritis

artrite reumatoide

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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 similar efficacy of GP2017 and US-licensed Humira® in patients with moderate to severe active RA with respect to DAS28-CRP score change from baseline to at Week 12.

Dimostrare la simile efficacia di GP2017 e del farmaco autorizzato negli USA Humira® in pazienti affetti da AR in fase attiva da moderata a grave in relazione alla variazione del punteggio di attività della malattia in 28 articolazioni (Disease Activity Score 28, DAS28) con PCR dal basale alla Settimana 12.

E.2.2

Secondary objectives of the trial

To demonstrate similar efficacy of GP2017 and US-licensed Humira with respect to time-weighted averaged change from baseline in DAS28-CRP until Week 24.
To compare the proportion of GP2017 and US-licensed Humira treated patients achieving European League against Rheumatism (EULAR) criterion for remission, good response and moderate response
To compare the proportion of GP2017 and US-licensed Humira treated patients achieving ACR20/50/70 responses
To compare Health Assessment Questionnaire-Disability Index (HAQ-DI) changes from baseline in GP2017 and US-licensed Humira treated patients
To compare Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale changes from baseline in GP2017 and US-licensed Humira treated patients
To compare clinical safety of GP2017 and US-licensed Humira



Dimostrare simile efficacia di GP2017 e farmaco autorizzato negli USA Humira® in relazione alla variazione media ponderata per tempo del DAS28-PCR dal basale fino a Settimana 24
Confrontare percentuale di pazienti trattati con GP2017 e con Humira® che soddisfa criterio per la remissione della Lega europea contro le malattie reumatiche (European League against Rheumatism, EULAR) di buona e moderata risposta
Confrontare percentuale pazienti trattati con GP2017 e con Humira® che ottiene risposte del 20/50/70 secondo i criteri del Collegio americano di reumatologia (ACR20/50/70)
Confrontare variazioni rispetto al basale dell’Indice di invalidità secondo il Questionario di valutazione della salute (HAQ-DI) in pazienti trattati con GP2017 e con Humira®
Confrontare variazioni rispetto al basale sulla scala dell’affaticamento della Valutazione funzionale della terapia per malattia cronica (FACIT) in pazienti trattati con GP2017 e con Humira®
Confrontare sicurezza clinica di GP17 e Humira®

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patients must have been diagnosed with RA ≥ 6 months prior to screening
2.Patients must have active disease, defined as DAS28-CRP ≥ 3.2 at the time of screening
3.Patients must have CRP levels above 5mg/l or ESR levels above the upper limits of normal
4.Patients must have had inadequate clinical response to MTX 10 - 25 mg/week.

1. I pazienti devono aver ricevuto una diagnosi di AR ≥6 mesi prima dello screening
2. I pazienti devono presentare malattia in fase attiva, definita come DAS28-PCR ≥3,2 al momento dello screening
3. I pazienti devono presentare livelli di PCR superiori a 5 mg/l o livelli di VES al di sopra dei limiti superiori di normalità
4. I pazienti devono aver avuto una risposta clinica inadeguata a MTX 10-25 mg/settimana

E.4

Principal exclusion criteria

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
1. Previous treatment with adalimumab, other anti-TNFα therapies or cell depleting agents, e.g. anti-CD20 therapy
2. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during treatment.
3. Nursing (lactating) or pregnant women
4. History of or ongoing inflammatory or autoimmune diseases other than RA, e.g. mixed connective tissue disease, systemic lupus erythematosus etc.
5. Systemic corticosteroids > 7.5mg/day within 4 weeks prior to baseline
6. History or presence of cancer or lymphoproliferative disease other than a successfully and completely treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix and/or removed non-invasive colon polyps, with no evidence of recurrence
7. History of uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (New York Heart Association III-IV), active peptic ulcer disease, recent stroke (within 3 months)
8. Subject known to have immune deficiency, positive human immunodeficiency virus (HIV) status or immunocompromised for other reasons
9. History of clinically significant hematologic (e.g. severe anemia, leucopenia, thrombocytopenia), renal or liver disease (e.g. glomerulonephritis, fibrosis, cirrhosis, hepatitis)
10. History of persistent chronic infection; recurrent infection or active infections
11. History of tuberculosis, presence of active tuberculosis, latent tuberculosis as detected by imaging (e.g. chest X-ray, chest Computerized Tomography(CT) scan, Magnetic Resonance Imaging (MRI)) and/ or positive QuantiFERON-TB Gold test (QFT)
12. History or evidence of opportunistic infections, e.g. histoplasmosis, listeriosis, legionellosis
13. Positive serology Hepatitis B (either HBsAg or anti-HBc) or Hepatitis C (positive HCV-Ab or HCV-RNA) indicative of previous or current infections

I pazienti che soddisfano uno qualunque dei seguenti criteri non sono ritenuti idonei per l’inclusione in questo studio:
1. Precedente trattamento con adalimumab, altro agente anti-fattore di necrosi tumorale alfa (anti-TNFα), terapie o agenti di deplezione cellulare, ad es. terapia anti-CD20
2. Donne fertili, definite come tutte le donne fisiologicamente in grado di avviare una gravidanza, a meno che non utilizzino metodi contraccettivi altamente efficaci
3. Donne in allattamento o in gravidanza
4. Anamnesi pregressa o attuale di malattie infiammatorie o autoimmuni diverse dalla AR, ad es. malattia mista del tessuto connettivo, lupus eritematoso sistemico, ecc.
5. Corticosteroidi per via sistemica a dosi >7,5 mg/die nelle 4 settimane precedenti il basale
6. Anamnesi o presenza di neoplasia o malattia linfoproliferativa diversa da carcinoma squamocellulare o basocellulare della cute, non metastatico, efficacemente e completamente trattato e/o carcinoma localizzato in situ della cervice e/o polipi non invasivi del colon sottoposti a rimozione, senza alcuna evidenza di recidiva
7. Anamnesi di diabete non controllato, cardiopatia ischemica instabile, insufficienza cardiaca congestizia (classe III-IV secondo la classificazione della New York Heart Association [Associazione dei cardiologi di New York]), ulcera peptica attiva, ictus recente (entro 3 mesi)
8. Soggetti con anamnesi nota di immunodeficienza, positività per il virus dell’immunodeficienza umana (HIV) o immunocompromissione da altre cause
9. Anamnesi di malattia ematologica (ad es., grave anemia, leucopenia, trombocitopenia), renale o epatica (ad es., glomerulonefrite, fibrosi, cirrosi, epatite) clinicamente significativa
10. Anamnesi di infezione cronica persistente, infezione ricorrente o infezioni attive
11. Anamnesi di tubercolosi, presenza di tubercolosi attiva, tubercolosi latente rilevata mediante esami di diagnostica per immagini (ad es., radiografia del torace, tomografia computerizzata [TAC] del torace, risonanza magnetica) e/o test QuantiFERON®-TB Gold (QFT) positivo
12. Anamnesi o evidenza di infezioni opportunistiche, ad es. istoplasmosi, listeriosi, legionellosi
13. Sierologia positiva per epatite B (HBsAg o anti-HBc) o epatite C (positività degli anticorpi anti-virus dell’epatite C [HCV-Ab] o dell’HCV-RNA), indicativa di infezioni pregresse o in corso.

E.5 End points

E.5.1

Primary end point(s)

Meseaure of the score DAS28-CRP to assess the equivalence between the 2 tretaments.

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline
and week 12

E.5.2

Secondary end point(s)

Time-weighted averaged change from baseline in DAS28-CRP until Week 24

E.5.2.1

Timepoint(s) of evaluation of this end point

baseline and week 24

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

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

Yes

E.6.11

Pharmacogenomic

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

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

Czech Republic

France

Germany

Hungary

Italy

Korea, Republic of

Malaysia

Mexico

Poland

Romania

Russian Federation

Serbia

Spain

Turkey

United Kingdom

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

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:

278

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

145

F.4.2.2

In the whole clinical trial

308

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)

It is the investigator’s responsibility to provide follow-up medical care for all patients after the end of the study

E' responsabilità dello sperimentatore di fornire il cure mediche di follow-up per tutti i pazienti dopo la fine dello studio.

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

2016-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-08

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

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