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

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2010-024393-19-PL
• Date of registration: 12/03/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen, Inc.
• Public title: A Randomized, Double-blind, Active-controlled Study to Evaluate the Efficacy and Safety of Denosumab Compared With Risedronate in Glucocorticoid-treated Individuals
• Scientific title: A Randomized, Double-blind, Active-controlled Study to Evaluate the Efficacy and Safety of Denosumab Compared With Risedronate in Glucocorticoid-treated Individuals
• Date of first enrolment: 08/04/2012
• Target sample size: 776
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024393-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, United States

Contacts

• Name: IHQ Medical Info – Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info – Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

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.


Are the trial subjects under 18? no
Number of subjects for this age range:
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

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 bea

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Glucocorticoid-induced osteoporosis
MedDRA version: 18.1 Level: LLT Classification code 10031287 Term: Osteoporosis steroid-induced System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Prolia
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Denosumab
CAS Number: 615258-40-7
Current Sponsor code: AMG 162
Other descriptive name: Immunoglobulin G2 Human Monoclonal Antibody to RANK Ligand
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Actonel
Product Name: Actonel
Pharmaceutical Form: Capsule
INN or Proposed INN: Risedronate Sodium
CAS Number: 115436-72-1
Current Sponsor code: SUB04252MIG
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: 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

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).

Timepoint(s) of evaluation of this end point: Month 12

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: Months 12 and 24

Secondary ID(s)

2010-024393-19-BE

20101217

Source(s) of Monetary Support

Amgen, Inc.