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

Phase 1

• Conditions: Glucocorticoid-induced osteoporosis; MedDRA version: 14.1Level: LLTClassification code 10031287Term: Osteoporosis steroid-inducedSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2010-024393-19-FR
• Lead Sponsor: Amgen, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-08-14
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 776

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 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.
4.1.3 Ambulatory
4.1.4 At least two lumbar vertebrae from L1 through L4 and one hip must be evaluable by DXA (duplicate scans required)
4.1.5 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
Initiated administration of any of the following 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)
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 that, in
the opinion of the investigator, might compromise the safety of
the subject.
Evidence of any ofEvidence 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 (eg,
osteopetrosis, osteogenesis imperfecta) (chart review)
Abnormalities of the following per central laboratory reference ranges
• Vitamin D deficiency (25[OH] vitamin D level < 20 ng/mL
[< 49.9 nmol/L]). Vitamin D replenishment will be permitted and
subjects may be re-screened
• 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 (except cervical carcinoma in situ or basal cell carcinoma)
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 con

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified