Transition From Alendronate to Romosozumab (AMG 785)

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01588509
• Collaborator: (none)
• Enrollment: 60
• Locations: 9
• Arms: 2
• Actual Duration (Months): 7.8
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to estimate the percent change from baseline in lumbar spine bone mineral density (BMD) following multiple-dose administrations of romosozumab in postmenopausal women with low BMD previously treated with alendronate.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis	Drug: Romosozumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized Study to Estimate the Percent Change From Baseline in Lumbar Spine Bone Mineral Density After 3 Months of AMG 785 Administration in Postmenopausal Women With Low Bone Mineral Density Previously Treated With Alendronate
• Actual Study Start Date: Mar 30, 2012
• Actual Primary Completion Date: Nov 21, 2012
• Actual Study Completion Date: Nov 21, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Romosozumab 140 mg Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 EVENITY™
Experimental: Romosozumab 210 mg Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 EVENITY™

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine [Baseline and day 85]

   Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and analyzed by a central imaging lab.

Secondary Outcome Measures

1. Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck [Baseline and day 85]

   Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.

2. Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip [Baseline and day 85]

   Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.

3. Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP) [Baseline and days 4, 15, 29, 43, 57, 71, and 85]

4. Percent Change From Baseline in Serum C-telopeptide (sCTX) [Baseline and days 4, 15, 29, 43, 57, 71, and 85]

5. Number of Participants With Adverse Events [From first dose of study drug up to day 85]

   An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. A treatment-related adverse event (TRAE) was an adverse event assessed by the investigator as possibly related to the investigational product, indicated by a "yes" response to the question: Is there a reasonable possibility that the event may have been caused by the investigational product? A serious adverse event was defined as an adverse event that met at least 1 of the following serious criteria: fatal, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, and/or other medically important serious event.

6. Number of Participants Who Developed Anti-romosozumab Antibodies [Baseline and days 29, 57, and 85]

   Two validated assays were used to detect the presence of anti-romosozumab antibodies. An electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Samples testing positive in the immunoassay were further tested in a competitive binding bioassay for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity, the participant was defined as positive for neutralizing antibodies. Participants who developed anti-romosozumab antibodies were those with a negative result at baseline and a positive result at any time postbaseline.

7. Mean Serum Concentration of Romosozumab [Days 4, 15, 29, 43, 57, 71 and 85]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal women, defined as no vaginal bleeding or spotting for ≥ 12 months

• Low bone mineral density at screening [defined by a bone mineral density (BMD) T-score ≤ -2.0 and ≥ -4.0 at the lumbar spine (L1 to L4; or BMD T-score of evaluable vertebrae), total hip, or femoral neck]

• Currently taking alendronate (70 mg weekly or equivalent) exclusively for ≥ 1 year with verbal agreement that the subject has taken ≥ 80% of their doses with good tolerance

Exclusion Criteria:

• History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis after age 50; or recent bone fracture within 6 months prior to screening

• History of metabolic or bone disease such as Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome

• Vitamin D deficiency (defined as 25-OH-VitD levels < 20 ng/mL)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tucson	Arizona	United States	85711
2	Research Site	Walnut Creek	California	United States	94598
3	Research Site	Gainesville	Georgia	United States	30501
4	Research Site	Honolulu	Hawaii	United States	96813
5	Research Site	Bethesda	Maryland	United States	20817
6	Research Site	Albuquerque	New Mexico	United States	87106
7	Research Site	West Haverstraw	New York	United States	10993
8	Research Site	Wyomissing	Pennsylvania	United States	19610
9	Research Site	Seattle	Washington	United States	98144

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01588509
• Other Study ID Numbers: 20110253
• First Posted: May 1, 2012
• Last Update Posted: Mar 26, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Amgen: AMG 785, bone mineral density, alendronate
• Additional relevant MeSH terms: Osteoporosis

Study Results

Participant Flow

Recruitment Details	This study was conducted at 8 centers in the United States. The first participant enrolled on 30 March 2012 and the last participant enrolled on 21 August 2012.

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Period Title: Overall Study
STARTED	30	30
Received Treatment	30	30
COMPLETED	29	30
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg	Total
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.	Total of all reporting groups
Overall Participants	30	30	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.6 (7.5)	66.7 (8.3)	66.1 (7.8)
Age, Customized (Count of Participants)
< 65 years	14 46.7%	15 50%	29 48.3%
≥ 65 years	16 53.3%	15 50%	31 51.7%
Sex: Female, Male (Count of Participants)
Female	30 100%	30 100%	60 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 40%	14 46.7%	26 43.3%
Not Hispanic or Latino	18 60%	16 53.3%	34 56.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	5 16.7%	2 6.7%	7 11.7%
Black (or African American)	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	2 6.7%	2 3.3%
Other	0 0%	1 3.3%	1 1.7%
White	25 83.3%	25 83.3%	50 83.3%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine
Description	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and analyzed by a central imaging lab.
Time Frame	Baseline and day 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug and with non-missing baseline and day 85 measurements.

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	29	30
Mean (Standard Error) [percent change]	2.13 (0.64)	2.08 (0.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Romosozumab 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Percent Change from Baseline
	Estimated Value	2.13
	Confidence Interval	(2-Sided) 90%; 1.05 to 3.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Romosozumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Percent Change from Baseline
	Estimated Value	2.08
	Confidence Interval	(2-Sided) 90%; 1.02 to 3.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck
Description	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Time Frame	Baseline and day 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug and with non-missing baseline and day 85 measurements.

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	29	30
Mean (Standard Error) [percent change]	2.06 (0.59)	1.92 (0.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Romosozumab 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Percent Change from Baseline
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 90%; 1.07 to 3.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Romosozumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Percent Change from Baseline
	Estimated Value	1.92
	Confidence Interval	(2-Sided) 90%; 0.95 to 2.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip
Description	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Time Frame	Baseline and day 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug and with non-missing baseline and day 85 measurements.

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	29	30
Mean (Standard Error) [percent change]	1.38 (0.34)	1.40 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Romosozumab 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Percent Change from Baseline
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 90%; 0.81 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Romosozumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Percent Change from Baseline
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 90%; 0.84 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Time Frame	Baseline and days 4, 15, 29, 43, 57, 71, and 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug and with available data at each time point

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	30	30
Day 4	22.1263 (3.3852)	30.4935 (4.9950)
Day 15	140.9970 (15.1975)	218.4994 (22.6148)
Day 29	128.3936 (17.7834)	221.9954 (23.3718)
Day 43	164.1654 (17.7832)	251.0495 (23.4572)
Day 57	99.3682 (14.9155)	168.7689 (17.1565)
Day 71	127.4051 (14.8572)	205.2619 (23.5171)
Day 85	64.9103 (10.5005)	142.5601 (20.3233)

5. Secondary Outcome

Title	Percent Change From Baseline in Serum C-telopeptide (sCTX)
Time Frame	Baseline and days 4, 15, 29, 43, 57, 71, and 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug and with available data at each time point

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	30	30
Day 4	-28.2149 (3.9352)	-14.8099 (4.6844)
Day 15	-28.9365 (4.6974)	-22.2800 (5.1854)
Day 29	3.1008 (8.6448)	-1.8188 (7.4121)
Day 43	3.4511 (8.9913)	11.0131 (10.0244)
Day 57	25.7433 (8.7440)	35.7697 (13.5346)
Day 71	28.4465 (11.7345)	44.3802 (13.7159)
Day 85	54.0549 (14.2140)	61.1734 (13.9874)

6. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. A treatment-related adverse event (TRAE) was an adverse event assessed by the investigator as possibly related to the investigational product, indicated by a "yes" response to the question: Is there a reasonable possibility that the event may have been caused by the investigational product? A serious adverse event was defined as an adverse event that met at least 1 of the following serious criteria: fatal, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, and/or other medically important serious event.
Time Frame	From first dose of study drug up to day 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	30	30
All adverse events	14 46.7%	15 50%
Serious adverse events	0 0%	0 0%
AE leading to discontinuation of study drug	0 0%	0 0%
AE leading to discontinuation from study	0 0%	0 0%
Fatal adverse events	0 0%	0 0%
Treatment-related adverse events	3 10%	4 13.3%
Treatment-related serious adverse events	0 0%	0 0%
TRAE leading to discontinuation of study drug	0 0%	0 0%
TRAE leading to discontinuation from study	0 0%	0 0%
Treatment-related fatal adverse events	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants Who Developed Anti-romosozumab Antibodies
Description	Two validated assays were used to detect the presence of anti-romosozumab antibodies. An electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Samples testing positive in the immunoassay were further tested in a competitive binding bioassay for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity, the participant was defined as positive for neutralizing antibodies. Participants who developed anti-romosozumab antibodies were those with a negative result at baseline and a positive result at any time postbaseline.
Time Frame	Baseline and days 29, 57, and 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	30	30
Binding antibody positive	2 6.7%	2 6.7%
Neutralizing antibody positive	0 0%	0 0%

8. Secondary Outcome

Title	Mean Serum Concentration of Romosozumab
Time Frame	Days 4, 15, 29, 43, 57, 71 and 85

Outcome Measure Data

Analysis Population Description

All participants who received study drug with available data at each time point.

Arm/Group Title	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
Measure Participants	30	30
Day 4	15000 (6350)	23200 (9730)
Day 15	10500 (3540)	18500 (6640)
Day 29	3890 (2000)	8200 (4470)
Day 43	14300 (4280)	22800 (9390)
Day 57	5490 (2600)	10700 (6380)
Day 71	13700 (5000)	22700 (10500)
Day 85	5350 (3190)	11600 (6850)

Adverse Events

Time Frame	From first dose of study drug up to day 85
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Romosozumab 140 mg		Romosozumab 210 mg
Arm/Group Description	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.		Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
All Cause Mortality
	Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/30 (36.7%)		6/30 (20%)
General disorders
Fatigue	3/30 (10%)		0/30 (0%)
Injection site reaction	0/30 (0%)		2/30 (6.7%)
Oedema peripheral	0/30 (0%)		2/30 (6.7%)
Infections and infestations
Nasopharyngitis	2/30 (6.7%)		1/30 (3.3%)
Upper respiratory tract infection	1/30 (3.3%)		2/30 (6.7%)
Injury, poisoning and procedural complications
Contusion	2/30 (6.7%)		1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/30 (10%)		1/30 (3.3%)
Muscle spasms	2/30 (6.7%)		0/30 (0%)
Musculoskeletal pain	2/30 (6.7%)		0/30 (0%)

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.