Clinical Trials Register

Summary
EudraCT Number:	2013-003467-60
Sponsor's Protocol Code Number:	M13-741
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:	2014-05-29
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

2013-003467-60

A.3

Full title of the trial

A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients with Knee Osteoarthritis

Studio di Fase 2a per valutare la sicurezza, l’efficacia e gli effetti farmacodinamici di ABT-981 in pazienti con l’osteoartrosi del ginocchio

A.3.1

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

A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients with Knee Osteoarthritis

Studio di Fase 2a per valutare la sicurezza, l’efficacia e gli effetti farmacodinamici di ABT-981 in pazienti con l’osteoartrosi del ginocchio

A.4.1

Sponsor's protocol code number

M13-741

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	AbbVie Deutschland GmbH & Co. KG
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	AbbVie 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	Abbvie Ltd
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Abbott house, Vanwall Business Park, Vanwall
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441628773355
B.5.5	Fax number	+441628644330
B.5.6	E-mail	eu-clinical-trials@abbvie.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	ABT-981
D.3.2	Product code	ABT-981
D.3.4	Pharmaceutical form	Lyophilisate for 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	na
D.3.9.3	Other descriptive name	ABT-981
D.3.9.4	EV Substance Code	SUB127307
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	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	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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Lyophilisate for suspension for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Adult male and female patients with mild to moderate, symptomatic, radiographic and inflammatory osteoarthritis of the knee

Pazienti adulti uomini e donne con osteoartrosi del ginocchio da lieve a moderata, sintomatica, con evidenza radiografica e infiammatoria

E.1.1.1

Medical condition in easily understood language

Mild to moderate knee osteoarthritis

Osteoartrosi del ginocchio da lieve a moderata

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10031161
E.1.2	Term	Osteoarthritis
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 assess the effect of ABT-981 on OA knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at Week 16 and synovitis/effusion volume of the index knee using quantitative measures and semi-quantitative MRI scoring at Week 26 in patients with knee osteoarthritis.

Valutare gli effetti di ABT-981 sul dolore da osteoartrosi del ginocchio (OA) in base al punteggio WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) alla Settimana 16 e al volume di versamento/sinovite presente nel ginocchio di riferimento alla Settimana 26 mediante misure quantitative e punteggi di Risonanza magnetica semi-quantitativi in pazienti affetti da osteoartrosi del ginocchio.

E.2.2

Secondary objectives of the trial

n/a

N.A.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

1. PK substudy
2. Synovial Fluid substudy
3. DCE-MRI substudy

1. Sottostudio di Farmacocinetica
2. Sottostudio sul Fluido Sinoviale
3. Sottostudio sulle Risonanze Magnetiche con mezzo di contrasto

E.3

Principal inclusion criteria

1.Patient must have radiographic evidence of knee osteoarthritis in the medial compartment of the index knee with Kellgren-Lawrence Grade 2 or 3 (with minimum 2 mm joint space width) during Screening as evaluated by a qualified central imaging reader. Prior radiographs taken no more than 3 months before Study Day 1 with Synaflexer™ will be submitted for centralized eligibility reading.
2. Patient must have either constant or intermittent index knee pain at least 14 days over the past 30 days at screening. The intensity of index knee pain is between 4 and 8 out of 10, inclusive, at the initial Screening Visit and Study Day 1. The intensity of index knee pain is recorded as the average pain during the past week.
3.Patient has one or more clinical signs and symptoms of active inflammation in the index knee (localized pain, joint stiffness, swelling and effusion) during Screening and Study Day 1.
4.Presence of synovitis in the index knee confirmed by ultrasound during Screening.
5.Patient discontinued analgesics, non-steroidal anti-inflammatory drugs and nutraceuticals (e.g., glucosamine, chondroitin sulfate, shark cartilage, diacerein, soy extract) at least 7 days prior to first dose of study drug until after Week 26 MRI visit.

1. Paziente con evidenza radiografica di osteoartrosi del ginocchio a carico del compartimento mediale del ginocchio di riferimento, di Grado 2 o 3 della scala Kellgren-Lawrence (con spessore dello spazio articolare minimo di 2 mm) durante lo Screening, confermata da valutazione da parte di un lettore per imaging centralizzato qualificato. Saranno inviate per la valutazione centralizzata di eleggibilità radiografie pregresse purché eseguite non oltre 3 mesi prima del Giorno 1 della Sperimentazione, utilizzando il dispositivo di posizionamento Synaflexer™.
2. Il paziente deve avere dolore costante o intermittente al ginocchio di riferimento almeno 14 giorni negli ultimi 30 giorni allo screening. L’intensità del dolore al ginocchio di riferimento è tra 4 e 8 su 10, compreso, alla visita di screening iniziale e al giorno 1 della sperimentazione. L’intensità del dolore al ginocchio di riferimento è registrata come il dolore medio dell’ultima settimana.
3. Paziente che manifesta uno o più segni clinici e sintomi di infiammazione in fase attiva a carico del ginocchio di riferimento (dolore localizzato, rigidità, gonfiore e versamento articolare) nel corso dello Screening e al Giorno 1 della Sperimentazione.
4. Presenza di sinovite nel ginocchio di riferimento, confermata da ecografia durante lo Screening.
5. Paziente che ha interrotto il trattamento con analgesici, farmaci antinfiammatori non steroidei e prodotti nutraceutici (es., glucosammina, condroitina solfato, cartilagine di squalo, diacerina, estratto di soia) almeno 7 giorni prima di ricevere la prima dose del medicinale sperimentale fino alla risonanza magnetica della visita della Settimana 26.

E.4

Principal exclusion criteria

1.History of allergic reaction or significant sensitivity to any constituents of the study drug, history of anaphylactic reaction to any agent (e.g., food products or bee stings) or history of a major reaction to any IgG-containing product.
2.Significant trauma or surgery to the index knee within the last year or arthroscopy of the index knee within 6 months of Screening.
3.Kellgren-Lawrence Grade 1 or 4 in the index knee.
4.Severe knee malalignment, either greater than 2° in varus; or greater than 5° in valgus angulation in the index knee.
5.Diagnosis of one or more of the following:
a.Inflammatory arthritis such as rheumatoid arthritis, autoimmune disorder, seronegative spondyloarthropathy, gout, or pseudogout (defined as acute episodic attacks of swollen , painful joints in a patient with X-Ray chondrocalcinosis or CPPD crystals);
b.Other chronic painful syndromes (such as Paget's disease and fibromyalgia) and clinically significant non-articular musculoskeletal pain that could interfere with assessment of pain at the index knee.
6. History or evidence of active tuberculosis (TB)
7. Any uncontrolled medical illness or unstable treatment ot therapy.

1. Storia di reazioni allergiche o sensibilità significativa a uno qualsiasi dei componenti del medicinale sperimentale, storia di reazione anafilattica a qualsiasi agente (ad esempio, prodotti alimentari o veleno di imenotteri) oppure storia di reazione importante a qualsiasi prodotto contenente IgG.
2. Trauma o intervento chirurgico importante al ginocchio di riferimento nel corso dell’ultimo anno oppure artroscopia del ginocchio di riferimento nei 6 mesi precedenti lo Screening.
3. Classificazione Kellgren-Lawrence 1 o 4 del ginocchio di riferimento.
4. Allineamento patologico grave del ginocchio di riferimento, maggiore del 2° di varismo oppure maggiore del 5° di valgismo.
5. Diagnosi di una o più delle seguenti patologie:
• Forme di artrite infiammatoria quale ad esempio l’artrite reumatoide, patologie autoimmuni, spondiloartropatia sieronegativa, gotta oppure pseudo gotta (definita come attacchi episodici acuti di gonfiore e dolore articolare in paziente con evidenza radiografica di condrocalcinosi oppure artite microcristallina);
• Altre sindromi croniche dolorose (quali la malattia di Paget e la fibromialgia) e dolore muscolo-scheletrico extra-articolare clinicamente significativo che potrebbe interferire con la valutazione del dolore del ginocchio di riferimento.
6. Storia o evidenza di tubercolosi attiva.
7. Qualsiasi malattia medica incontrollata o un trattamento o terapia instabili.

E.5 End points

E.5.1

Primary end point(s)

The change from baseline to week 16 in OA knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and from baseline to week 26 in synovitis/effusion volume of the index knee using quantitative and semi-quantitative MRI scoring

Variazione dal baseline alla settimana 16 del dolore da Osteoartrosi al ginocchio, utilizzando il Western Ontario and McMaster Universities Ostearthritis Index (WOMAC) e la variazione dal baseline alla settimana 26 della sinovite/volume del versamento nel ginocchio di riferimento mediante parametri di Risonanza Magnetica quantitativi e semi-quantitativi.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 16 and Week 26

settimana 16 e settimana 26

E.5.2

Secondary end point(s)

● To evaluate the safety and tolerability of ABT-981 in patients with knee OA.
● To evaluate the effect of ABT-981 on physical function scores of the index knee at Weeks 16, 26 and 52 using WOMAC.
● To evaluate the effect of ABT-981 on index knee pain scores at Weeks 26 and 52 using WOMAC.
● To evaluate the effect of ABT-981 in reduction of bone marrow lesions (BML) of the index knee MRI at Weeks 26 and 52 using semi quantitative measurements (WORMS).
● To evaluate the effect of ABT-981 on index knee resting pain at Weeks 16, 26 and 52 using the Intermittent and Constant Osteoarthritis Pain (ICOAP) score.
● To evaluate the effect of ABT-981 on index knee resting pain at Weeks 16, 26 and 52 using the 11-point NRS scale (NRS-11).
● To evaluate the effect of ABT-981 on Patient Global Assessment of Arthritis at Weeks 16, 26 and 52.
● To evaluate the effect of ABT-981 on the preservation of cartilage volume/thickness of the index knee using MRI at Weeks 26 and 52.

Valutare la sicurezza e la tollerabilità di ABT-981 in pazienti con Osteoartrosi del ginocchio.
Valutare l’effetto di ABT-981 sul punteggio della funzionalità fisica del ginocchio di riferimento alle settimane 16, 26 e 52 utilizzando il WOMAC.
Valutare l’effetto di ABT-981 sul punteggio del dolore del ginocchio di riferimento alle settimane 26 e 52 utilizzando il WOMAC.
Valutare l’effetto di ABT-981 sulla riduzione delle lesioni midollari (bone –marrow lesion BML) delle Risonanze Magnetiche del ginocchio di riferimento alle settimane 26 e 52 utilizzando misure semi-quantitative (WORMS).
Valutare l’effetto di ABT-981 sul dolore a riposo del ginocchio di riferimento alle settimane 16, 26 e 52 utilizzando il punteggio Intermittent and Constant Osteoarthritis Pain (ICOAP).
Valutare l’effetto di ABT-981 sul dolore a riposo del ginocchio di riferimento alle settimane 16, 26 e 52 utilizzando la scala 11-point NRS.
Valutare l’effetto di ABT-981 sul Patient Global Assessment of Arthritis alle settimane 16, 26 e 52.
Valutare l’effetto di ABT-981 sulla Preservazione del volume/spessore della cartilagine del ginocchio di riferimento utilizzando RM alle settimane 26 e 52.

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 16, 26 and 52

settimana 16, settimana 26 e settimana 52

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

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

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)

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

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

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

Australia

Canada

Denmark

France

Germany

Italy

Mexico

Netherlands

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

Last subject last visit (LSLV)

Ultima Visita dell’Ultimo Soggetto

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.1.1.1

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:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

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

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

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

175

F.4.2.2

In the whole clinical trial

320

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)

Returm to standard of care

Ritorno allo standard terapeutico

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-06-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-09

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

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