Denosumab for Prevention of Post-Teriparatide Bone Loss in Premenopausal Women With IOP

• Sponsor: Elizabeth Shane (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02049866
• Collaborator: Creighton University (Other)
• Enrollment: 33
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 88.3
• Patients Per Site: 16.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to evaluate antiresorptive therapy with denosumab (Prolia) for prevention of bone loss after stopping teriparatide (TPTD) in premenopausal women with idiopathic osteoporosis.

Premenopausal women who have received TPTD in the FDA Orphan Diseases Program-funded trial, "A Phase 2 Study of Teriparatide for the Treatment of Idiopathic Osteoporosis in Premenopausal Women" (NCT01440803) may be eligible to participate in the current study, a 36-month open-label pilot study of denosumab (Prolia®, 60mg subcutaneous (SC) every 6 months).

The goals of the study are to estimate the effects of denosumab on central and peripheral, as well as trabecular and cortical, bone mass and microstructure and to obtain preliminary data to inform the design of a future randomized study. This study presents the first opportunity to study the effects of denosumab after TPTD in this unique and severely affected group of young women.

Funding Source: FDA Office of Orphan Products Development (OOPD).

Condition or Disease	Intervention/Treatment	Phase
Adult Idiopathic Generalized Osteoporosis	Drug: Denosumab	Phase 2

Detailed Description

Osteoporosis in premenopausal women with normal menstrual function and no specific cause is termed idiopathic osteoporosis (IOP). IOP is a rare disease with an estimated prevalence of <200,000 affected premenopausal women in the United States.

Denosumab, a potent inhibitor of osteoclast-mediated bone resorption, leads to continuous gains in both trabecular and cortical bone mineral density (BMD). Moreover, denosumab is not retained in the skeleton, and may thus be preferable for use in young women who may be contemplating future pregnancies. The investigators hypothesize that denosumab, initiated after completion of two years of TPTD, will maintain or improve central and peripheral areal and volumetric BMD, microstructure and stiffness in premenopausal women with IOP.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Denosumab for Prevention of Post-Teriparatide Bone Loss in Premenopausal Women With Idiopathic Osteoporosis (IOP)
• Actual Study Start Date: Nov 19, 2014
• Actual Primary Completion Date: Mar 31, 2020
• Anticipated Study Completion Date: Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Denosumab Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months.	Drug: Denosumab; Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months; Other Names: Prolia Xgeva

Outcome Measures

Primary Outcome Measures

1. Percent Change in Lumbar Spine Areal BMD by DXA [Baseline and 12 months]

   Bone mineral density (BMD) will be measured with dual-energy X-ray absorptiometry (DXA).

Secondary Outcome Measures

1. Percent Change in Lumbar Spine Areal BMD by DXA at 24 Months [Baseline and 24 months]

   Bone mineral density (BMD) will be measured with dual-energy X-ray absorptiometry (DXA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All women completing NCT01440803 who remain without a disease or medication that causes osteoporosis will be offered enrollment into this study.

• (Premenopausal status is no longer be required for entry.)

Exclusion Criteria:

• Renal insufficiency or liver disease: Creatinine, transaminase (AST)/alanine transaminase (ALT) above upper limit of normal

• Vitamin D deficiency: 25-hydroxyvitamin D (25-OHD) <30 ng/mL

• Pregnancy: urine pregnancy test must be negative

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Creighton University	Omaha	Nebraska	United States	68131
2	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Elizabeth Shane
• Creighton University

Investigators

• Principal Investigator: Elizabeth Shane, MD, Columbia University
• Principal Investigator: Adi Cohen, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 17, 2017

More Information

Additional Information:

• Columbia University, Dept of Medicine, Division of Endocrinology website

Publications

None provided.

• Responsible Party: Elizabeth Shane, Professor of Medicine, Columbia University
• ClinicalTrials.gov Identifier: NCT02049866
• Other Study ID Numbers: AAAN0161; 1R01FD005114-01A2
• First Posted: Jan 30, 2014
• Last Update Posted: Apr 21, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Elizabeth Shane, Professor of Medicine, Columbia University: osteoporosis; premenopausal; denosumab; idiopathic; Idiopathic Osteoporosis in Premenopausal Women
• Additional relevant MeSH terms: Osteoporosis; Denosumab

Study Results

Participant Flow

Arm/Group Title	Denosumab
Arm/Group Description	Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months. Denosumab: Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months
Period Title: Overall Study
STARTED	33
COMPLETED	32
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Denosumab
Arm/Group Description	Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months. Denosumab: Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months
Overall Participants	33
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	33 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39 (8)
Sex: Female, Male (Count of Participants)
Female	33 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	32 97%
More than one race	1 3%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Lumbar Spine Areal BMD by DXA
Description	Bone mineral density (BMD) will be measured with dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

33 participants completed baseline but 1 participant withdrew from the study before the 12 month visit.

Arm/Group Title	Denosumab
Arm/Group Description	Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months. Denosumab: Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months
Measure Participants	32
Mean (Standard Deviation) [percentage of change]	5.2 (2.6)

2. Secondary Outcome

Title	Percent Change in Lumbar Spine Areal BMD by DXA at 24 Months
Description	Bone mineral density (BMD) will be measured with dual-energy X-ray absorptiometry (DXA).
Time Frame	Baseline and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse event data was collected for 1 year (from baseline to 12 month study participation).
Arm/Group Title	Denosumab
Arm/Group Description	Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months. Denosumab: Denosumab 60mg, administered every 6 months by subcutaneous injection for 36 months
All Cause Mortality
	Denosumab
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Serious Adverse Events
	Denosumab
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Other (Not Including Serious) Adverse Events
	Denosumab
	Affected / at Risk (%)	# Events
Total	26/33 (78.8%)
Gastrointestinal disorders
Nausea and vomiting	2/33 (6.1%)	2
General disorders
Low Energy	4/33 (12.1%)	4
Infections and infestations
Urinary tract infection	12/33 (36.4%)	12
Ear infection	3/33 (9.1%)	3
Musculoskeletal and connective tissue disorders
Fracture	3/33 (9.1%)	3
Muscle cramps	4/33 (12.1%)	4
Pain in thighs, hips, or groin	11/33 (33.3%)	11
Joint pain	2/33 (6.1%)	2
Nervous system disorders
Numbness and/or tingling	6/33 (18.2%)	6
Respiratory, thoracic and mediastinal disorders
Cold	12/33 (36.4%)	12
Skin and subcutaneous tissue disorders
Eczema	2/33 (6.1%)	2
Rash	2/33 (6.1%)	2
Hair loss	3/33 (9.1%)	3
Surgical and medical procedures
Redness	2/33 (6.1%)	2
Pain	9/33 (27.3%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.