Denosumab in Primary Hyperparathyroidism

NCT01558115 | Terminated Phase 4 Results DMC FDA Drug

• 3 other identifiers: AAAF2568R01DK03233320090741
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Primary hyperparathyroidism (PHPT), a disease characterized by excess parathyroid hormone (PTH) and high blood calcium, is one of the most common endocrine disorders. PHPT is seen most often in postmenopausal women. Many patients with PHPT have low bone mineral density (BMD) when bone mass is measured by dual energy x-ray absorptiometry (DXA), primarily at the forearm. There is currently no effective medical therapy which increases bone density at the forearm in patients with PHPT. PTH both builds and breaks down bone, and the pathways by which PTH mediates these actions are beginning to be identified. Prior research suggests that RANKL, a molecule important in bone metabolism, responds to PTH, and that if the RANKL is inactivated, PTH is shifted towards building bone. The investigators will study the effect of Denosumab, a therapeutic agent that binds to and inactivates RANKL, in 28 postmenopausal women with PHPT. Our hypothesis is that Denosumab will increase bone mineral density in primary hyperparathyroidism. The study will last two years, and subjects will be randomly assigned to receive either placebo or Denosumab for the first year of the study. In the second year, all subjects will receive Denosumab. Denosumab (60 mg) or placebo will be given every 6 months by an injection just under the skin. Study procedures performed will include bone mineral density tests by DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans, and assessments of biochemical markers of calcium metabolism and bone turnover using both blood and urine samples of subjects with PHPT.

Conditions

Primary Hyperparathyroidism

Keywords

Columbia University; Primary hyperparathyroidism; Low bone density; Denosumab; Prolia

Outcome Measures

Primary Outcomes (1)

• Change in Bone Mineral Density (BMD) at the Lumbar Spine

  Percent change from baseline in BMD at the lumbar spine, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months

  Baseline and 12 months

Secondary Outcomes (2)

• Change in Bone Mineral Density (BMD) at the Distal 1/3 Radius

  12 months

• Change in Bone Mineral Density (BMD) at the Hip

  12 months

Study Arms (2)

Denosumab - Group #1

EXPERIMENTAL

Receive active drug for year 1 and year 2 of the study

Drug: Denosumab

Placebo - Group #2

PLACEBO COMPARATOR

Receive placebo for year 1 and active drug for year 2 of the study

Drug: Denosumab; Other: Placebo

Interventions

Denosumab DRUG

The dose of denosumab is 60 mg every 6 months by subcutaneous injection. The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2. Group # 1: Receive active drug for year 1 and year 2 of the study Group #2: Receive placebo for year 1 and active drug for year 2 of the study

Also known as: Prolia, Xgeva

Denosumab - Group #1; Placebo - Group #2

Placebo OTHER

The dose of denosumab is 60 mg every 6 months by subcutaneous injection. The placebo group will receive vehicle injections at the same time interval. The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2. Group # 1: Receive active drug for year 1 and year 2 of the study Group #2: Receive placebo for year 1 and active drug for year 2 of the study

Placebo - Group #2

Eligibility Criteria

• Age: 40 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed hypercalcemic PHPT in postmenopausal women with serum calcium \>10.2 mg/dL and \< 12.0 mg/dL (nl: 8.6-10.2)
• T-score between -1.5 and -2.5 at any site. If the T-score is \<-2.5, patients become candidates for parathyroid surgery. They will be enrolled only if they refuse the parathyroid surgery

You may not qualify if:

• hydroxyvitamin D level \< 20 ng/ml
• Previous use of the bisphosphonate zoledronic acid (ever), alendronate or risedronate (within 12 months) or ibandronate (within 6 months)
• Current use of PTH, glucocorticoids, SERMS, estrogen (other than vaginal), calcitonin or pharmacological amounts of calcitriol Current or previous use of cinacalcet (within 6 months)
• Hyperthyroidism
• Rheumatoid arthritis or any other inflammatory joint disease
• Paget's disease of bone
• Malabsorption
• T-score \<-3.5 at any site
• Signs of symptomatic PHPT (e.g, kidney stones within the past 5 years; fragility fracture within the past 2 years)
• Physical or mental handicapping condition that precludes ability to complete the protocol and/or provide informed consent.
• Subjects on Antiviral HIV therapy or subjects with compromised immune systems
• Premenopausal women or men
• Stage 5 Chronic Kidney Disease (CKD) or anyone on dialysis
• Creatinine clearance \< 30 cc/min unless the patient is not a candidate for surgery or if the patient refuses surgery

Sponsors & Collaborators

• Columbia University: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Amgen: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Hyperparathyroidism, Primary; Bone Diseases, Metabolic

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Data was not collected and analyzed as per protocol due to study closing prematurely because of poor enrollment.

Results Point of Contact

• Title: John P. Bilezikian, MD
• Organization: Columbia University

jpb2@cumc.columbia.edu

212-305-6257

Study Officials

• John P Bilezikian, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2012
• First Posted: March 20, 2012
• Study Start: January 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: November 2, 2022
• Results First Posted: November 2, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)