Clinical Trials Register

Summary
EudraCT Number:	2010-024393-19
Sponsor's Protocol Code Number:	20101217
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-02-08
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

Czechia - SUKL

A.2

EudraCT number

2010-024393-19

A.3

Full title of the trial

A Randomized, Double-blind, Active-controlled Study to Evaluate the Efficacy and Safety of Denosumab Compared With Risedronate in Glucocorticoid-treated Individuals

Randomizovaná, dvojitě zaslepená, aktivně kontrolovaná studie hodnotící
účinnost a bezpečnost denosumabu v porovnání s risedronátem u pacientů
léčených glukokortikoidy.

A.3.1

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

A Study to Evaluate the Efficacy and Safety of Denosumab Compared with Risedronate in Glucocorticoid-treated Individuals

A.4.1

Sponsor's protocol code number

20101217

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	Amgen, 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	Amgen, 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	Amgen (EUROPE) GmbH
B.5.2	Functional name of contact point	IHQ Medical Info – Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	Dammstrasse 23, P.O. Box 1557
B.5.3.2	Town/ city	Zug
B.5.3.3	Post code	CH-6300
B.5.3.4	Country	Switzerland
B.5.6	E-mail	MedinfoInternational@amgen.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	Yes
D.2.1.1.1	Trade name	Prolia
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V
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	Denosumab
D.3.2	Product code	AMG 162
D.3.4	Pharmaceutical form	Solution for injection/infusion in pre-filled syringe
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	615258-40-7
D.3.9.2	Current sponsor code	AMG 162
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
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.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	Actonel
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	Risedronate sodium
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	115436-72-1
D.3.9.3	Other descriptive name	RISEDRONATE SODIUM
D.3.9.4	EV Substance Code	SUB04252MIG
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	5
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	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/infusion in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Glucocorticoid-induced osteoporosis

E.1.1.1

Medical condition in easily understood language

Osteoporosis

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

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	10031287
E.1.2	Term	Osteoporosis steroid-induced
E.1.2	System Organ Class	100000004859

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 in the glucocorticoid-continuing subpopulation of men and women treated with chronic glucocorticoid therapy is to demonstrate that treatment with denosumab 60 mg subcutaneously (SC) every 6 months (Q6M) is not inferior to treatment with oral risedronate 5 mg every day (QD) with respect to the percent change from baseline in lumbar spine bone mineral density (BMD) by dual X-ray absorptiometry (DXA) at 12 months.
The primary objective in the glucocorticoid-initiating subpopulation of men and women treated with glucocorticoid therapy is to demonstrate that treatment with denosumab 60 mg SC Q6M is not inferior to treatment with oral risedronate 5 mg QD with
respect to the percent change from baseline in lumbar spine BMD by DXA at 12 months.

E.2.2

Secondary objectives of the trial

To compare the effects of denosumab with that of risedronate separately in the glucocorticoid-continuing and glucocorticoid-initiating subpopulations on:
• Percent change from baseline in lumbar spine BMD by DXA at 12 months
• Percent change from baseline in total hip BMD by DXA at 12 months
• Percent change from baseline in lumbar spine BMD by DXA at 24 months
• Percent change from baseline in total hip BMD by DXA at 24 months

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Glucocorticoid-initiating subpopulation:
Men and women ≥ 18 years of age who have initiated
• Prednisone ≥ 7.5 mg daily or its equivalent within 3 months prior to screening and are expected to be treated with oral glucocorticoids for a total of at least 6 months
OR
− Glucocorticoid-continuing subpopulation:
Men and women ≥ 18 years of age who are taking
• Prednisone ≥ 7.5 mg daily or its equivalent for ≥ 3 months preceding screening and are expected to be treated with oral glucocorticoids for a total of at least 6 months.
4.1.2 Glucocorticoid-continuing subjects who are ≥ 50 years of age will be required to have a BMD value equivalent to a T-score ≤ -2.0 at the lumbar spine, total hip, or femoral neck; or a BMD value equivalent to a T-score ≤ -1.0 at the lumbar spine, total hip, or femoral neck and with a history of osteoporotic fracture.
4.1.3 Men and women < 50 years old at the time of screening in both glucocorticoid-continuing and glucocorticoid-initiating subpopulations, will be required to have a history of osteoporotic fracture.
4.1.4 Ambulatory
4.1.5 At least two lumbar vertebrae from L1 through L4 and one hip must be evaluable by DXA (duplicate scans required)
4.1.6 Subject or subject’s legally acceptable representative has provided informed consent prior to any study specific procedures.

E.4

Principal exclusion criteria

Received other OP treatment or bone active treatment with the following guidelines:
• Oral bisphosphonate use
- > 3 months cumulatively in the past 2 years, OR
- > 1 month in the past year, OR
• Any use during the 3-month period prior to screening
• Administration of intravenous bisphosphonate, fluoride or strontium for OP within the last 5 years
• Parathyroid hormone (PTH) or PTH derivatives within the last year
• Denosumab for OP at any time in the past
Administration of any of the following treatment within 3 months of screening:
• Any selective estrogen receptor modulator (SERM) (estrogen agonist/ antagonist)
• Tibolone
• Anabolic steroids or testosterone
• Systemic hormone replacement therapy
• Calcitonin
• Other bone active drugs including anti-convulsants (except
benzodiazepines) and heparin
• Chronic systemic ketoconazole, androgens, adrenocorticotropic
hormone (ACTH), cinacalcet, aluminum, lithium, protease inhibitors,
gonadotropin-releasing hormone agonists
Administration of any of the following biologic agents within 4 weeks prior to screening:
• Anti alpha 4 integrin antibody (eg, natalizumab)
• Anti CD4/CD8 T-cells (eg, alefacept)
• Anti IL-12/IL-23 (eg, ustekinumab)
• CTLA4 inhibitor (eg, abatacept)
• IL1 receptor antagonist (eg, anakinra)
• IL6 inhibitor (eg, tocilizumab)
• Monoclonal antibody to CD20 (eg, rituximab)
• TNF antagonist (eg, adalimumab, certolizumab, golimumab,
etanercept, infliximab)
• Administering >1 biologic agent for the treatment of underlying
inflammatory disease
Subject has an active infection or history of infections as follows:
• any active infection for which systemic anti-infectives were used
within 4 weeks prior to screening
• a serious infection, defined as requiring hospitalization or
intravenous anti-infectives within 8 weeks prior to screening
• recurrent or chronic infections or other active infection
Evidence of any of the following:
• History of hyperthyroidism (stable on antithyroid therapy is allowed)
• History of hypothyroidism (stable on thyroid replacement therapy is allowed)
• History of hypo- or hyperparathyroidism
• History of Addison disease
• History of osteomalacia
• History of osteonecrosis of the jaw
• History of recent tooth extraction or other dental surgery within the prior 6 months
• Invasive dental work planned in the next 2 years
• History of Paget’s disease of bone
• Other bone diseases which affect bone metabolism Abnormalities of the following per central laboratory reference ranges
• Vitamin D deficiency (25[OH] vitamin D level < 20 ng/mL
[< 49.9 nmol/L]).
• Hypercalcemia
• Elevated transaminases ≥ 2.0 x upper limit of normal (ULN)
• Elevated total bilirubin (TBL) > 1.5 x ULN
History of any solid organ or bone marrow transplant
Contraindicated to, or poorly tolerant of, denosumab therapy.
Contraindications include:
• Hypocalcemia
• Hypersensitivity to drug or any component of the drug
Contraindicated to, or poorly tolerant of, risedronate therapy:
• Hypocalcemia
• Abnormalities of the esophagus which delay esophageal emptying, such as stricture or achalasia
• Inability to stand or sit upright for at least 30 minutes
• Hypersensitivity to risedronate or other constituents of risedronate tablets
• Significantly impaired renal function as determined by a derived
glomerular filtration rate (GFR)
Known intolerance to calcium supplements
Currently pregnant or planning a pregnancy
For women of child bearing potential: Refusal to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication:
• Women not of childbearing potential include any female who
is postmenopausal and/or permanentlysterilized. Postmenopausal women are those who fit into one of the following categories:
− Age ≥ 55 years, with cessation of menses for 12 or more
months
− Age < 55 years, but no spontaneous menses for at least 2
years
− Age < 55 years and spontaneous menses within the past 1
year, but currently amenorrheic , AND with documented
postmenopausal gonadotropin levels
− Underwent a bilateral oophorectomy
- Currently lactating
- Self-reported or known alcohol or drug abuse within the previous
12 months
- Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s)
- Subject previously has entered this study
- Subject will not be available for protocol-required study visits or
procedures, to the best of the subject and investigator’s knowledge
- Any condition or illness (acute, chronic, or history), which might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject
- Subject has any kind of disorder that may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint in each of the subpopulations is percent change from baseline in lumbar spine BMD by DXA at 12 months (non-inferiority).

E.5.1.1

Timepoint(s) of evaluation of this end point

Month 12

E.5.2

Secondary end point(s)

Secondary endpoints to be evaluated in each of the subpopulations separately are:
• Percent change from baseline in lumbar spine BMD by DXA at 12 months
• Percent change from baseline in total hip BMD by DXA at 12 months
• Percent change from baseline in lumbar spine BMD by DXA at 24 months
• Percent change from baseline in total hip BMD by DXA at 24 months

E.5.2.1

Timepoint(s) of evaluation of this end point

Months 12 and 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

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

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

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

Argentina

Belgium

Canada

Czech Republic

Denmark

France

Germany

Hungary

Korea, Republic of

Mexico

Netherlands

Poland

Russian Federation

Spain

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

The time when the last subject is assessed or receives an
intervention for evaluation in the study at the 24 month visit.

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:

504

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

272

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

168

F.4.2

For a multinational trial

F.4.2.1

In the EEA

590

F.4.2.2

In the whole clinical trial

776

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)

Normal treatment for condition

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

2012-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-06-29

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