A Safety and Efficacy Study to Evaluate Romosozumab (AMG 785) in South Korean Women With Osteoporosis

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02791516
• Collaborator: (none)
• Enrollment: 67
• Locations: 10
• Arms: 2
• Actual Duration (Months): 23.1
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective is to evaluate the effect of treatment with romosozumab for 6 months compared with placebo on percent changes in bone mineral density (BMD) at the lumbar spine as assessed by dual-energy X-ray absorptiometry (DXA) in postmenopausal women with osteoporosis.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: Romosozumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Compare the Efficacy and Safety of Romosozumab With Placebo in Postmenopausal South Korean Women With Osteoporosis
• Actual Study Start Date: Jan 16, 2017
• Actual Primary Completion Date: Feb 12, 2018
• Actual Study Completion Date: Dec 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo subcutaneous injection once a month for 6 months.	Drug: Placebo; Administered by subcutaneous injections once a month
Experimental: Romosozumab Participants received 210 mg romosozumab by subcutaneous injection once a month for 6 months.	Drug: Romosozumab; Administered by subcutaneous injection once a month (QM); Other Names: AMG 785 Evenity

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline to Month 6 in Bone Mineral Density at the Lumbar Spine [Baseline and month 6]

   Bone mineral density (BMD) at the lumbar spine was assessed by dual-energy x-ray absorptiometry (DXA). Images were assessed by a central reader.

Secondary Outcome Measures

1. Percent Change From Baseline to Month 6 in Bone Mineral Density at the Total Hip [Baseline and month 6]

   Bone mineral density (BMD) at the total hip was assessed by dual-energy x-ray absorptiometry (DXA). Images were assessed by a central reader.

2. Percent Change From Baseline to Month 6 in Bone Mineral Density at the Femoral Neck [Baseline and month 6]

   Bone mineral density (BMD) at the femoral neck was assessed by dual-energy x-ray absorptiometry (DXA). Images were assessed by a central reader.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 90 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ambulatory postmenopausal Korean women, ≥ 55 to ≤ 90 years of age at enrollment.

• Postmenopause is defined as no spontaneous vaginal bleeding or spotting for 12 or more consecutive months prior to screening.

• BMD T-score </= -2.50 at the lumbar spine, total hip or femoral neck.

• At least 2 vertebrae in the L1 through L4 region and at least one hip are evaluable by DXA.

• Other inclusion criteria may apply.

Exclusion Criteria:

• Subjects with a BMD T-score </= -4.0 at the lumbar spine, total hip, or femoral neck.

• History of hip fracture.

• Bone disease other than osteoporosis/ or evidence of any other clinically significant disorder, condition/ or disease or significant laboratory abnormalities.

• Known sensitivity or intolerance calcium and vitamin D products.

• Other exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Busan		Korea, Republic of	602-739
2	Research Site	Gwangju		Korea, Republic of	501-757
3	Research Site	Namdong-gu, Incheon		Korea, Republic of	21565
4	Research Site	Seongnam Si Gyeonggi Do		Korea, Republic of	463-707
5	Research Site	Seoul		Korea, Republic of	120-752
6	Research Site	Seoul		Korea, Republic of	135-710
7	Research Site	Seoul		Korea, Republic of	136-705
8	Research Site	Seoul		Korea, Republic of	138-736
9	Research Site	Seoul		Korea, Republic of	150-713
10	Research Site	Suwon-si, Gyeonggi-do		Korea, Republic of	443-380

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2017
• Statistical Analysis Plan - Mar 9, 2018

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02791516
• Other Study ID Numbers: 20150242
• First Posted: Jun 6, 2016
• Last Update Posted: Oct 7, 2019
• Last Verified: Sep 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Amgen: Osteoporosis.; Osteoporosis-Postmenopausal.; Bone Diseases-Metabolic.; Bone Diseases.; Musculoskeletal Diseases.
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal

Study Results

Participant Flow

Recruitment Details	This study was conducted at 10 centers in South Korea. Participants were enrolled from 16 January 2017 to 17 August 2017.
Pre-assignment Detail	Participants were randomized in a 1:1 ratio to receive either romosozumab 210 mg subcutaneously (SC) QM or matched placebo SC QM. Upon completion of the 6-month treatment period, participants were followed for an additional 3 months.

Arm/Group Title	Placebo	Romosozumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injection once a month for 6 months.	Participants received 210 mg romosozumab by subcutaneous injection once a month for 6 months.
Period Title: Overall Study
STARTED	33	34
Completed 6-month Treatment Period	33	33
COMPLETED	32	33
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Placebo	Romosozumab 210 mg	Total
Arm/Group Description	Participants received placebo subcutaneous injection once a month for 6 months.	Participants received 210 mg romosozumab by subcutaneous injection once a month for 6 months.	Total of all reporting groups
Overall Participants	33	34	67
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.4 (7.2)	66.7 (7.6)	67.5 (7.4)
Age, Customized (Count of Participants)
< 65 years	13 39.4%	14 41.2%	27 40.3%
≥ 65 to < 75 years	13 39.4%	16 47.1%	29 43.3%
≥ 75 years	7 21.2%	4 11.8%	11 16.4%
Sex: Female, Male (Count of Participants)
Female	33 100%	34 100%	67 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	33 100%	34 100%	67 100%
Lumbar Spine Bone Mineral Density (BMD) T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.6483 (0.6450)	-2.6622 (0.8155)	-2.6554 (0.7310)
Total Hip BMD T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.1797 (0.6243)	-2.1515 (0.7114)	-2.1654 (0.6650)
Femoral Neck BMD T-score (T-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [T-score]	-2.5309 (0.5395)	-2.4494 (0.6069)	-2.4896 (0.5718)

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline to Month 6 in Bone Mineral Density at the Lumbar Spine
Description	Bone mineral density (BMD) at the lumbar spine was assessed by dual-energy x-ray absorptiometry (DXA). Images were assessed by a central reader.
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

Randomized participants who had a baseline DXA BMD measurement and at least 1 postbaseline DXA BMD measurement at the lumbar spine.

Arm/Group Title	Placebo	Romosozumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injection once a month for 6 months.	Participants received 210 mg romosozumab by subcutaneous injection once a month for 6 months.
Measure Participants	31	33
Least Squares Mean (Standard Error) [percent change]	-0.1 (0.8)	9.5 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model adjusting for treatment, baseline DXA BMD value, machine type, and machine type-by-baseline DXA BMD value.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.6
	Confidence Interval	(2-Sided) 95%; 7.6 to 11.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline to Month 6 in Bone Mineral Density at the Total Hip
Description	Bone mineral density (BMD) at the total hip was assessed by dual-energy x-ray absorptiometry (DXA). Images were assessed by a central reader.
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

Randomized participants who had a baseline DXA BMD measurement and at least 1 postbaseline DXA BMD measurement at the total hip.

Arm/Group Title	Placebo	Romosozumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injection once a month for 6 months.	Participants received 210 mg romosozumab by subcutaneous injection once a month for 6 months.
Measure Participants	31	33
Least Squares Mean (Standard Error) [percent change]	0.3 (0.4)	2.9 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model adjusting for treatment, baseline DXA BMD value, machine type, and machine type-by-baseline DXA BMD value.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; 1.4 to 3.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline to Month 6 in Bone Mineral Density at the Femoral Neck
Description	Bone mineral density (BMD) at the femoral neck was assessed by dual-energy x-ray absorptiometry (DXA). Images were assessed by a central reader.
Time Frame	Baseline and month 6

Outcome Measure Data

Analysis Population Description

Randomized participants who had a baseline DXA BMD measurement and at least 1 postbaseline DXA BMD measurement at the femoral neck.

Arm/Group Title	Placebo	Romosozumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injection once a month for 6 months.	Participants received 210 mg romosozumab by subcutaneous injection once a month for 6 months.
Measure Participants	31	33
Least Squares Mean (Standard Error) [percent change]	0.8 (0.7)	3.0 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments	ANCOVA model adjusting for treatment, baseline DXA BMD value, machine type, and machine type-by-baseline DXA BMD value.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; 0.7 to 3.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Adverse Events

Time Frame	9 months
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Placebo		Romosozumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injection once a month for 6 months.		Participants received 210 mg romosozumab by subcutaneous injection once a month for 6 months.
All Cause Mortality
	Placebo		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/34 (0%)
Serious Adverse Events
	Placebo		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/33 (6.1%)		0/34 (0%)
Infections and infestations
Pulmonary tuberculosis	1/33 (3%)		0/34 (0%)
Injury, poisoning and procedural complications
Femur fracture	1/33 (3%)		0/34 (0%)
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	1/33 (3%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/33 (12.1%)		2/34 (5.9%)
Infections and infestations
Nasopharyngitis	2/33 (6.1%)		1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Back pain	2/33 (6.1%)		1/34 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.