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

• Register: EUCTR
• Last refreshed on: 28 August 2017
• Main ID: EUCTR2010-024393-19-ES
• Date of registration: 05/03/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen, Inc.
• Public title: A 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: 24/04/2012
• 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.

- Men and women < 50 years old at the time of screening in both
glucocorticoid-continuing and glucocorticoid-initiating subpopulations, will be required to have either:
• History of osteoporotic fracture, OR
• BMD values at the lumbar spine or total hip in the protocol specified range

- Ambulatory
- At least two lumbar vertebrae from L1 through L4 and one hip must be evaluable by DXA (duplicate scans required)
- 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

- 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 osteomalacia
• History of osteonecrosis of the jaw
• History of recent tooth extraction or other dental surgery
• 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
- Malignancy within the last 5 years
- 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.
Contraindications for risedronate therapy include:
• 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) using Cockroft Gault formula of
= 30 mL/min/1.73 m2 calculated by the central laboratory

- 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
- 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 in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromi

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

Health Condition(s) or Problem(s) studied

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

Glucocorticoid-induced osteoporosis
MedDRA version: 14.1 Level: LLT Classification code 10031287 Term: Osteoporosis steroid-induced System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Prolia
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: 615258-40-7
CAS Number: AMG 162
Concentration unit: mg/l milligram(s)/litre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for injection/infusion in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Actonel
Product Name: Risedronate sodium
Pharmaceutical Form: Tablet
CAS Number: 115436-72-1
Other descriptive name: RISEDRONATE SODIUM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is percent change from baseline in lumbar spine BMD by DXA at 12 months (non-inferiority).

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 BMD by DXA at lumbar spine and total hip at 12 months
• Percent change from baseline in BMD by DXA at lumbar spine and total hip at 24 months

Timepoint(s) of evaluation of this end point: percent change from baseline in lumbar spine BMD by DXA at 12 months (non-inferiority).

Main Objective: In the glucocorticoid-continuing subpopulation of men and women treated with chronic glucocorticoid therapy (= 7.5 mg daily prednisone or its equivalent for = 3 months and are planning to continue treatment for a total of at least 6 months): 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.

In the glucocorticoid-initiating subpopulation of men and women treated with glucocorticoid therapy (= 7.5 mg daily prednisone or its equivalent for < 3 months and are
planning to continue treatment for a total of at least 6 months): 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 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 and total hip BMD by DXA at 12 months
• Percent change from baseline in lumbar spine and total hip BMD by DXA at 24 months

Timepoint(s) of evaluation of this end point: In each of the sub-populations separately are:

• Percent change from baseline in lumbar spine and total hip BMD by DXA at 12 months and 24 months

Secondary ID(s)

2010-024393-19-BE

20101217

Source(s) of Monetary Support

Amgen, Inc.