Clinical Trials Register

Summary
EudraCT Number:	2009-016604-23
Sponsor's Protocol Code Number:	CACZ885I2207
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-11-17
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

Germany - PEI

A.2

EudraCT number

2009-016604-23

A.3

Full title of the trial

A multi-center, double-blind, placebo-controlled, randomized study to compare the effect of a subcutaneous canakinumab administration to placebo in patients with Impaired Glucose Tolerance or patients with Type 2 Diabetes treated with differing baseline diabetes therapies.

A.4.1

Sponsor's protocol code number

CACZ885I2207

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
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	Yes
D.2.1.1.1	Trade name	Ilaris
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd.
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.3.1	Product name	Canakinumab
D.3.2	Product code	ACZ885
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Canakinumab
D.3.9.1	CAS number	914613-48-2
D.3.9.2	Current sponsor code	ACZ885
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	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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	Recombinant human monoclonal antibody

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	Powder for 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

Impaired Glucose Tolerance and Type 2 Diabetes

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10012594
E.1.2	Term	Diabetes

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to evaluate canakinumab effects on change from baseline of meal challenge derived insulin secretion rate relative to glucose 0-2 hours (Φd), at 4 weeks, on the following populations:
a. patients with T2DM pre-treated and continuing on stable metformin monotherapy
b. patients with T2DM pre-treated and continuing on a stable metformin dose in combination with a sulfonylurea
c. metformin in combination with a sulfonylurea and a thiazolidinedione
d. treatment with at least two insulin injections a day with or without metformin
e. in patients with impaired glucose tolerance (IGT)

E.2.2

Secondary objectives of the trial

1. evaluate the effect on the populations stated in the primary objective on change from baseline of meal challenge derived parameters, Φs, Φtotal, insulin sensitivity index, glucose disposition indices, area under curve of time glucose concentration and glycemic control parameters
2. evaluate canakinumab effects on change from baseline of meal challenge derived parameters as a function of baseline meal challenge glucose parameters including PPG and maximal glycemic excursion
3. provide proof of principle for improving post prandial and impaired fasting glucose in people with IGT as measured by Φd
4. compare the change from baseline of Φd between ACZ885 and placebo in the IGT population
5. assess the safety and tolerability of ACZ885 vs. placebo as an add-on regimen over 4 weeks in patients with T2DM on the populations stated in the primary objective
6. assess the safety and tolerability of ACZ885 vs. placebo over 4 weeks in patients with impaired glucose tolerance (IGT)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must give written informed consent before any study related procedures are performed.
2. Patient must fulfill all criteria in one of the following groups:
a. Impaired Glucose Tolerance (IGT) as defined by WHO criteria confirmed during the Screening Visit.
-Morning fasting plasma glucose concentration less than 126 mg/dl (7.0 mmol/l)
-Two hour plasma glucose concentration from Oral Glucose Tolerance Test (OGTT) of 75 g oral glucose ingestion greater than 140 mg/dl (7.8 mmol/l), but less than 200 mg/dl (11.1 mmol/l)
-Will not be started on an anti-diabetic medicine during the course of screening/run-in or treatment periods
b. Documented diagnosis of Type 2 diabetes in stable metformin monotherapy
-be on stable metformin monotherapy treatment at a dose at least 1000 mg/day for at least three months at Screening
-*take metformin as their first and only treatment with anti-diabetes drug therapy
(except for short term treatment courses with insulin in connection with hospitalization, etc.)
c. Documented diagnosis of Type 2 diabetes in stable treatment with metformin in combination with a sulfonylurea
-be on stable metformin and sulfonylurea combination therapy treatment for at
least three months at Screening
-Metformin dose at least 1000 mg/day at screening
-Sulfonylurea dose at least half of the maximally labeled dose for the specific drug
-Never have been in more than dual oral treatment for diabetes (except for short
term treatment courses with insulin in connection with hospitalization, etc.)
d. Documented diagnosis of Type 2 diabetes in stable treatment with metformin, sulfonylurea and thiazolidinedione combination therapy
-be on stable metformin and sulfonylurea and thiazolidinedione combination therapy treatment for at least three months at Screening
-Metformin dose at least 1000 mg/day at screening
-Sulfonylurea dose at least half of the maximally labeled dose for the specific drug
-Thiazolidinedione dose at least half of the maximally labeled dose for the specific drug
e. Documented diagnosis of Type 2 diabetes in stable treatment with at least two insulin injections (of any type of insulin or insulins) a day with or without metformin
-be on stable treatment with at least two injections of insulin with or without metformin for at least three months at Screening
-Total daily insulin dose less than 100 U.
3. At the Randomization Visit, patient must still be on the same regimen/dose of antidiabetic medication(s) as at the Screening Visit; does not apply to IGT group.
4. Have an HbA1c between 6.5% and 8%, inclusive, at Screening analyzed by the Central Laboratory; this criterion does not apply to the IGT group
5. Age from 18-74 years, inclusive, and of either sex.

E.4

Principal exclusion criteria

1. Type 1 diabetes, diabetes that is a result of pancreatic injury or other secondary forms of diabetes
2. Any of the following significant laboratory abnormalities:
• Serum GAD-antibody positivity analyzed by the Central Laboratory.
• Clinically significant TSH outside of normal range as judged by the Investigator at Screening analyzed by the Central Laboratory. One retest during the screening period may be allowed per Sponsor approval.
• Renal function indicating high risk metformin use, including serum creatinine concentrations (≥1.5 mg/dL for males, ≥1.4 mg/dL for females) or other evidence of abnormal creatinine clearance.
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Screening, confirmed with repeat measure within one week.
• Total bilirubin >2 times ULN and/or direct bilirubin greater than the ULN at Screening, confirmed by a repeat measurement within one week.
3. History or current findings of active pulmonary disease (e.g. tuberculosis, fungal diseases) as evidenced by any of the following:
• History of positive PPD skin test result followed by positive chest x-ray/positive QFT-G test and no completion of treatment.
• A positive PPD skin test followed by a positive chest x-ray or positive QFT(-G) test (with or without positive chest x-ray) during the screening period.
• History of a positive QFT(-G) test and no completion of treatment.
• History of a positive AFB sputum sample and no completion of treatment.
• Requirement for administration of antibiotics against latent tuberculosis (e.g., isoniazide). Courses of antibiotic therapy started prior to entering the study should not be prematurely terminated to allow inclusion into the study.
4. One of the risk factors for TB such as:
• History of any of the following: residence in a congregate setting (e.g. jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g. injection or non-injection); health-care workers with unprotected exposure to patients who are at high risk of TB or patients with TB disease before the identification and correct airborne precautions of the patient, or
• Close contact {i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)} with a person with active pulmonary TB disease.
5. Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven or suspected to be related to immunocompromisation, including patients with evidence of Human Immunodeficiency Virus (HIV) infection.
6. Known presence or suspicion of active or recurrent Hepatitis B and Hepatitis C infections (based on history and/or findings from the Central Lab).
7. Known chronic liver disease of any aetiology.
8. Any surgical or underlying hepatic, hematologic, pulmonary, infectious, autoimmune or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in immunodulatory therapy.
9. Any systemic treatment or local treatment of any immune modulating agent in doses with systemic effects. Topical, inhaled or local steroid use, in doses that are not considered to cause systemic effects, are permitted.
10. Live vaccinations within 3 months prior to the Randomization Visit or live vaccinations planned during the trial and up to three months following the last dose. Killed vaccines, including killed Seasonal Influenza and killed H1N1 Influenza vaccines are permitted.
11. Stroke, myocardial infarction, acute coronary syndrome, revascularization procedure or recurrent TIA within the last 6 months.
12. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
13. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
14. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation.
16. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are
• women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
• women whose partners have been sterilized by vasectomy or other means
• using a highly effective method of birth control

E.5 End points

E.5.1

Primary end point(s)

Evaluate canakinumab effects on change from baseline of meal challenge derived insulin secretion rate relative to glucose 0-2 hours (Φd), at 4 weeks

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)

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.8.3

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

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

please refer to chapter 3.1 of the protocol

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.1.1.1	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	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
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	60
F.4.2	For a multinational trial
F.4.2.1	In the EEA	107
F.4.2.2	In the whole clinical trial	232

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

2010-01-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-05-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-08-06

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