Trial Outcomes & Findings for Transition From Alendronate to Romosozumab (AMG 785) (NCT NCT01588509)
NCT ID: NCT01588509
Last Updated: 2019-03-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
60 participants
Primary outcome timeframe
Baseline and day 85
Results posted on
2019-03-26
Participant Flow
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.
Participant milestones
| Measure |
Romosozumab 140 mg
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
30
|
|
Overall Study
Received Treatment
|
30
|
30
|
|
Overall Study
COMPLETED
|
29
|
30
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Romosozumab 140 mg
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Transition From Alendronate to Romosozumab (AMG 785)
Baseline characteristics by cohort
| Measure |
Romosozumab 140 mg
n=30 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.6 years
STANDARD_DEVIATION 7.5 • n=99 Participants
|
66.7 years
STANDARD_DEVIATION 8.3 • n=107 Participants
|
66.1 years
STANDARD_DEVIATION 7.8 • n=206 Participants
|
|
Age, Customized
< 65 years
|
14 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
|
Age, Customized
≥ 65 years
|
16 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=99 Participants
|
30 Participants
n=107 Participants
|
60 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black (or African American)
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
25 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
50 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and day 85Population: All participants who received study drug and with non-missing baseline and day 85 measurements.
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.
Outcome measures
| Measure |
Romosozumab 140 mg
n=29 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine
|
2.13 percent change
Standard Error 0.64
|
2.08 percent change
Standard Error 0.63
|
SECONDARY outcome
Timeframe: Baseline and day 85Population: All participants who received study drug and with non-missing baseline and day 85 measurements.
Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Outcome measures
| Measure |
Romosozumab 140 mg
n=29 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck
|
2.06 percent change
Standard Error 0.59
|
1.92 percent change
Standard Error 0.58
|
SECONDARY outcome
Timeframe: Baseline and day 85Population: All participants who received study drug and with non-missing baseline and day 85 measurements.
Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Outcome measures
| Measure |
Romosozumab 140 mg
n=29 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip
|
1.38 percent change
Standard Error 0.34
|
1.40 percent change
Standard Error 0.34
|
SECONDARY outcome
Timeframe: Baseline and days 4, 15, 29, 43, 57, 71, and 85Population: All participants who received study drug and with available data at each time point
Outcome measures
| Measure |
Romosozumab 140 mg
n=30 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Day 85
|
64.9103 percent change
Standard Error 10.5005
|
142.5601 percent change
Standard Error 20.3233
|
|
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Day 4
|
22.1263 percent change
Standard Error 3.3852
|
30.4935 percent change
Standard Error 4.9950
|
|
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Day 15
|
140.9970 percent change
Standard Error 15.1975
|
218.4994 percent change
Standard Error 22.6148
|
|
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Day 29
|
128.3936 percent change
Standard Error 17.7834
|
221.9954 percent change
Standard Error 23.3718
|
|
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Day 43
|
164.1654 percent change
Standard Error 17.7832
|
251.0495 percent change
Standard Error 23.4572
|
|
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Day 57
|
99.3682 percent change
Standard Error 14.9155
|
168.7689 percent change
Standard Error 17.1565
|
|
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)
Day 71
|
127.4051 percent change
Standard Error 14.8572
|
205.2619 percent change
Standard Error 23.5171
|
SECONDARY outcome
Timeframe: Baseline and days 4, 15, 29, 43, 57, 71, and 85Population: All participants who received study drug and with available data at each time point
Outcome measures
| Measure |
Romosozumab 140 mg
n=30 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Day 4
|
-28.2149 percent change
Standard Error 3.9352
|
-14.8099 percent change
Standard Error 4.6844
|
|
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Day 15
|
-28.9365 percent change
Standard Error 4.6974
|
-22.2800 percent change
Standard Error 5.1854
|
|
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Day 29
|
3.1008 percent change
Standard Error 8.6448
|
-1.8188 percent change
Standard Error 7.4121
|
|
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Day 43
|
3.4511 percent change
Standard Error 8.9913
|
11.0131 percent change
Standard Error 10.0244
|
|
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Day 57
|
25.7433 percent change
Standard Error 8.7440
|
35.7697 percent change
Standard Error 13.5346
|
|
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Day 71
|
28.4465 percent change
Standard Error 11.7345
|
44.3802 percent change
Standard Error 13.7159
|
|
Percent Change From Baseline in Serum C-telopeptide (sCTX)
Day 85
|
54.0549 percent change
Standard Error 14.2140
|
61.1734 percent change
Standard Error 13.9874
|
SECONDARY outcome
Timeframe: From first dose of study drug up to day 85Population: All participants who received study drug
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.
Outcome measures
| Measure |
Romosozumab 140 mg
n=30 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Number of Participants With Adverse Events
All adverse events
|
14 Participants
|
15 Participants
|
|
Number of Participants With Adverse Events
Serious adverse events
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
AE leading to discontinuation of study drug
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
AE leading to discontinuation from study
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Fatal adverse events
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Treatment-related adverse events
|
3 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events
Treatment-related serious adverse events
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
TRAE leading to discontinuation of study drug
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
TRAE leading to discontinuation from study
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Treatment-related fatal adverse events
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and days 29, 57, and 85Population: All participants who received study drug
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.
Outcome measures
| Measure |
Romosozumab 140 mg
n=30 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Number of Participants Who Developed Anti-romosozumab Antibodies
Binding antibody positive
|
2 Participants
|
2 Participants
|
|
Number of Participants Who Developed Anti-romosozumab Antibodies
Neutralizing antibody positive
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Days 4, 15, 29, 43, 57, 71 and 85Population: All participants who received study drug with available data at each time point.
Outcome measures
| Measure |
Romosozumab 140 mg
n=30 Participants
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 Participants
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
Mean Serum Concentration of Romosozumab
Day 4
|
15000 ng/mL
Standard Deviation 6350
|
23200 ng/mL
Standard Deviation 9730
|
|
Mean Serum Concentration of Romosozumab
Day 15
|
10500 ng/mL
Standard Deviation 3540
|
18500 ng/mL
Standard Deviation 6640
|
|
Mean Serum Concentration of Romosozumab
Day 29
|
3890 ng/mL
Standard Deviation 2000
|
8200 ng/mL
Standard Deviation 4470
|
|
Mean Serum Concentration of Romosozumab
Day 43
|
14300 ng/mL
Standard Deviation 4280
|
22800 ng/mL
Standard Deviation 9390
|
|
Mean Serum Concentration of Romosozumab
Day 57
|
5490 ng/mL
Standard Deviation 2600
|
10700 ng/mL
Standard Deviation 6380
|
|
Mean Serum Concentration of Romosozumab
Day 71
|
13700 ng/mL
Standard Deviation 5000
|
22700 ng/mL
Standard Deviation 10500
|
|
Mean Serum Concentration of Romosozumab
Day 85
|
5350 ng/mL
Standard Deviation 3190
|
11600 ng/mL
Standard Deviation 6850
|
Adverse Events
Romosozumab 140 mg
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Romosozumab 210 mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Romosozumab 140 mg
n=30 participants at risk
Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
|
Romosozumab 210 mg
n=30 participants at risk
Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.
|
|---|---|---|
|
General disorders
Fatigue
|
10.0%
3/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Injection site reaction
|
0.00%
0/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
6.7%
2/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
General disorders
Oedema peripheral
|
0.00%
0/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
6.7%
2/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
2/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
3.3%
1/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Infections and infestations
Upper respiratory tract infection
|
3.3%
1/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
6.7%
2/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Injury, poisoning and procedural complications
Contusion
|
6.7%
2/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
3.3%
1/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
3/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
3.3%
1/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
2/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.7%
2/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
0.00%
0/30 • From first dose of study drug up to day 85
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER