Clinical Trials Register

Summary
EudraCT Number:	2013-005535-24
Sponsor's Protocol Code Number:	ABROGATE-5527
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-12-03
Trial 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

UK - MHRA

A.2

EudraCT number

2013-005535-24

A.3

Full title of the trial

Abatacept (CTLA4-Ig) for the treatment of relapsing, non-severe, granulomatosis with polyangiitis (Wegener's)

A.3.1

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

Abatacept (CTLA4-Ig) for the Treatment of Relapsing, Non-Severe, Granulomatosis with Polyangiitis (Wegener’s) (ABROGATE)

A.3.2

Name or abbreviated title of the trial where available

ABROGATE

A.4.1

Sponsor's protocol code number

ABROGATE-5527

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02108860

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	Univeristy of South Florida
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bristol Myers Squibb (BMS)
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	Department of Rheumatology
B.5.2	Functional name of contact point	Center for Vasculitis Care and Rese
B.5.3	Address:
B.5.3.1	Street Address	9500 Euclid Avenue, A50
B.5.3.2	Town/ city	Cleveland, OH 44195
B.5.3.4	Country	United States
B.5.4	Telephone number	(216) 445-6056
B.5.6	E-mail	langfoc@ccf.org

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	Yes
D.2.1.1.1	Trade name	Orencia
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol Myers Squibb
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Abatacept
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	Abatacept
D.3.9.1	CAS number	332348-12-6
D.3.9.4	EV Substance Code	AS1
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	125
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)	Yes
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	Solution 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

Granulomatosis with polyangiitis (GPA; Wegener's granulomatosis)

E.1.1.1

Medical condition in easily understood language

GPA (Wegener's Granulomatosis), a type of systemic vasculitis characterised by inflammation of the small blood vessels, including capillaries.

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	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10047889
E.1.2	Term	Wegeners granulomatosis
E.1.2	System Organ Class	100000004866

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10047888
E.1.2	Term	Wegener's granulomatosis
E.1.2	System Organ Class	100000004866

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10050894
E.1.2	Term	Anti-neutrophil cytoplasmic antibody positive vasculitis
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Does abatacept improve the control of disease in GPA/Wegeners and allow reduction in the dose of glucocorticoids usually used to control disease symptoms.

E.2.2

Secondary objectives of the trial

• Duration of glucocorticoid-free periods
• Duration of remission with abatacept versus placebo
• Severity of relapses in those treated with abatacept versus placebo
• Health-related quality of life in those treated with abatacept versus placebo
• Prevention of disease- or treatment-related damage with abatacept versus placebo
• Safety of abatacept in GPA

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must have met at least 2 of the 5 modified ACR classification criteria for GPA. These do not need to be present at the time of study entry. The modified ACR criteria are:
a. Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge
b. Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities
c. Active urinary sediment, defined as microscopic hematuria (> 5 red blood cells per high power field) or red blood cell casts
d. Granulomatous inflammation on biopsy, defined as histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area (artery or arteriole)
e. Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3 measured by enzyme-linked immunoassay
2. Relapse of GPA within the 28 days prior to screening where the active disease features meet the following definition of non-severe disease:
a. No disease manifestations that would be scored as a major element in the BVAS/WG (49)
b. Absence of any disease feature that poses an immediate threat to either a critical individual organ or the patient’s life
3. Age of 15 years or older
4. Willing and able to comply with treatment and follow-up procedures
5. Both women and men must be willing to use an effective means of birth control while receiving treatment through this study. Effective contraception methods include abstinence, oral contraceptives (birth control pills), IUD, diaphragm, Norplant, approved hormone injections, condoms, or medical sterilization.
6. Willing and able to provide written informed consent with the written assent of those < 18 years of age.

E.4

Principal exclusion criteria

1. Presence of involvement that does not meet the criteria for non-severe disease
2. Treatment with CYC within 3 months prior to screening
3. Treatment with methylprednisolone 1000 mg within 28 days prior to enrollment
4. Treatment with prednisone > 30 mg/day for > 28 days immediately prior to study entry
5. Initiation or dose increase of the maintenance immunosuppressive agent (MTX, AZA, MA) within 3 months prior to screening
6. Evidence of active infection (includes chronic infection)
7. Patients who are pregnant or who are nursing infants
8. Known infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen
9. Inability to comply with study guidelines
10. Cytopenia: platelet count < 100,000/mm3, white blood cell count (WBC) < 3,000/mm3 (3 x 109/L), absolute neutrophil count < 1500/mm3, hemoglobin (Hgb) < 8.5 g/dL
11. Chronic renal insufficiency defined by a creatinine clearance of less than or equal to 20 ml/min
12. Known current use of illegal drugs
13. Other uncontrolled disease (co-morbidity) that could prevent a patient from fulfilling the study requirements or that would substantially increase the risk of study procedures
14. History of malignancy within the past five years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure
15. Receipt of an investigational agent or device within 30 days prior to enrollment or 5 half lives of the investigational drug (whichever is longer)
16. A live vaccination fewer than 3 months before enrollment
17. Current clinical, radiographic, or laboratory evidence of active tuberculosis
18. A history of active tuberculosis within the past 3 years even if treated
19. A history of active tuberculosis greater than 3 years ago unless there is documentation of prior anti-tuberculosis treatment of appropriate duration and type
20. Latent tuberculosis unless there is documentation of prior anti-tuberculosis treatment of appropriate duration and type
21. Latent tuberculosis currently being treated with isoniazid (INH) or other therapy for latent tuberculosis given according to local health authority guidelines (e.g., Center for Disease Control) who have received such therapy for 4 weeks or less prior to randomization (Day 1). Subjects with a positive tuberculosis screening test indicative of latent tuberculosis will be eligible for the study if they have no evidence of current tuberculosis on chest x-ray at screening and they are actively being treated for tuberculosis with INH or other therapy for latent tuberculosis given according to local health authority guidelines (e.g., Center for Disease Control) that has been given for at least 4 weeks prior to randomization (Day 1). These subjects must complete treatment according to local health authority guidelines.
22. History of herpes zoster that resolved less than 2 months prior to enrollment
23. Treatment with rituximab or any other biologic B cell depleting agent within the past 6 months, or past treatment with rituximab or any other biologic B cell deleting agent where the B lymphocyte count remains < 60 cells/uL
24. Treatment with alemtuzumab or anti-thymocyte globulin within the last 12 months
25. Treatment with intravenous immunoglobulin or plasma exchange within the past 3 months
26. Treatment with infliximab, etanercept, adalimumab, tocilizumab, or any other biologic agent within the past 3 months or 5 half lives of the agent (whichever is longer)

E.5 End points

E.5.1

Primary end point(s)

Ability of abatacept to reduce the treatment failure rate through 12 months

Treatment failure will be defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) = 0 or 1 by 6 months

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months
12 months

E.5.2

Secondary end point(s)

Duration of glucocorticoid-free periods
Duration of remission with Abatacept-v-placebo
Severity of relapses with Abatacept-v-placebo
Health-related Quality of Life outcomes with abatacept-v-placebo
Prevention of disease or treatment-related damage with Abatacept-v-placebo
Safety of Abatacept-v-placebo

E.5.2.1

Timepoint(s) of evaluation of this end point

entire study duration (up to 2 years for patients)
3 months post-treatment (safety assessment)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

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

France

Ireland

Italy

Mexico

Spain

Sweden

Switzerland

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

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

Yes

F.1.1