STARTT-Hip: Study To Assess FRacTure Healing With SclerosTin Antibody - Hip

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01081678
• Collaborator: (none)
• Enrollment: 332
• Locations: 99
• Arms: 4
• Actual Duration (Months): 34.7
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an international, multi-center study to determine the efficacy, safety, and tolerability of romosozumab (AMG 785) in adults with a fresh unilateral hip fracture, status post surgical fixation.

Condition or Disease	Intervention/Treatment	Phase
Fracture Healing	Drug: Placebo; Drug: Romosozumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 332 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy, Safety, and Tolerability of AMG 785 in Adults With a Fresh Unilateral Hip Fracture, Status Post Surgical Fixation
• Actual Study Start Date: Jun 20, 2010
• Actual Primary Completion Date: Jun 30, 2012
• Actual Study Completion Date: May 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Placebo; Administered by subcutaneous (under the skin) injection
Experimental: Romosozumab 70 mg Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 Evenity
Experimental: Romosozumab 140 mg Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 Evenity
Experimental: Romosozumab 210 mg Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785 Evenity

Outcome Measures

Primary Outcome Measures

1. Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 [Weeks 6, 12, 16, and 20]

   Functional healing was measured by the timed-up-and-go test (TUG) over Weeks 6 through 20. During this assessment, the clinician timed the participant while they stood up from a seated position in a chair, walked three meters, turned around, walked three meters back to the chair, and returned to the seated position. A TUG value of ten seconds or less was considered normal for a healthy elderly person. Higher TUG values after hip fracture have been shown to be a predictor of future falls. Least squares mean (LSM) estimates were based on a repeated measures model fitted with the log-transformed TUG values at weeks 2, 6, 12, 16, 20, 24, 36, 52 as the dependent variable and adjusted for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction and back-transformed using the exponential transformation.

Secondary Outcome Measures

1. Timed-Up-and-Go (TUG) at Each Visit [Weeks 2, 6, 12, 16, 20, 24, 36, and 52]

   During the timed-up-and-go test the clinician timed the participant while they stood up from a seated position in a chair, walked 3 meters, turned around, walked 3 meters back to the chair, and returned to a seated position. A TUG value of ≤ 10 seconds is considered normal for a healthy elderly person. LSMs were based on a repeated measures model adjusting for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction. Missing TUG values for participants still on study were imputed using the last observation carried forward (LOCF) when possible. If no observation could be carried forward, the maximum TUG value observed among all participants at a given visit was used. TUG values obtained after unplanned revision surgery were replaced by carrying forward the last available observed or imputed value prior to unplanned revision surgery.

2. Time to Radiographic Healing [52 weeks]

   Time to radiographic healing is the time interval from the surgery date for the eligible hip fracture to the date of radiographic healing, defined as effacement of the fracture lines by newly formed bone along the cortices and within the trabecular bone on anteroposterior and lateral (or oblique) radiographs. Radiographic fracture healing was determined by a panel of independent reviewers blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.

3. Radiographic Union Scale for Hip (RUSH) Score At Each Visit [Weeks 2, 6, 12, 16, 20, 24, 36, and 52]

   The radiographic Union Scale for Hip (RUSH) is a semiquantitative scoring assessment to assess hip fracture healing after surgical repair. The RUSH has 4 key domains based on radiographic parameters used by orthopedic surgeons and radiologists in routine clinical practice including cortical bridging (4 to 12 points), cortical fracture line disappearance (4 to 12 points), trabecular consolidation (1 to 3 points), and trabecular index disappearance of fracture line (1 to 3 points). The score has a minimum of 10 points (definitely not healed) and a maximum of 30 points (definitely healed).

4. Harris Hip Score At Each Visit [Weeks 2, 6, 12, 16, 20, 24, 36, and 52]

   The Harris Hip Score is a clinician-based outcome that assesses pain, function, deformity, and range of motion. The pain domain measures pain severity and its effect on activities and need for pain medication. The function domain consists of daily activities and gait. Deformity takes into account hip flexion, adduction, internal rotation, and extremity length discrepancy. Range of motion measures hip flexion, abduction, external and internal rotation, and adduction. The score ranges form 0-100 (best possible outcome) covering pain (0-44 points), function (0-47 points), absence of deformity (4 points), and range of motion (5 points). LSMs were based on a repeated measures model fitted with the Harris hip score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.

5. Hip Pain Score at Each Visit [Weeks 2, 6, 12, 16, 20, 24, 36, and 52]

   Hip pain was assessed using a visual analog scale (VAS). Participants were asked to rate their pain as a result of the hip fracture on a 100 mm vertical scale with 0 indicating no pain at all and 100 indicating the worst pain they could imagine. LSMs were based on a repeated measures model fitted with hip pain score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females, age 55 to 95 years

• fresh unilateral low energy intertrochanteric or femoral neck fracture as the primary injury, confirmed by X-ray and in the opinion of the treating surgeon amenable to repair by internal fixation

• internal fixation of the fracture with devices approved by local regulatory agency, performed no later than 7 days after injury for intertrochanteric or undisplaced femoral neck fractures and no later than 2 days after injury for displaced femoral neck fractures

• intertrochanteric fracture: sliding hip screw or IM nail

• femoral neck fracture: sliding hip screw or at least 3 cancellous screws

Exclusion Criteria:

• severe symptomatic osteoarthritis of the lower extremity

• inability to independently rise from armchair or walk 200 meters before hip fracture

• presence of concomitant injuries such as rib fractures, wrist fractures, or acute symptomatic vertebral fractures which severely impair the ability to rise from a chair

• associated extremity injuries including ipsilateral or contralateral fractures of the foot, tibia or fibula, wrist, humerus, femoral shaft, femoral head or hip dislocation, that may delay weight-bearing beyond one week after surgery

• head-injury, as defined by Glasgow Coma Scale < 13 prior to randomization

• use of bone grafts or bone substitutes at the time of fracture fixation

• major polytrauma or significant axial trauma, with Injury Severity Score > 16

• pathological fracture or history of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as Paget's disease, rheumatoid arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia

• history of symptomatic spinal stenosis that has not been surgically corrected. If surgically corrected, the subject must be asymptomatic to be eligible for the study.

• history of facial nerve paralysis

• malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical carcinoma in situ) within the last 5 years

• history of solid organ or bone marrow transplants

• evidence of elevated transaminases (≥ 2.0 x upper limits of normal) or significantly impaired renal function (creatinine clearance of ≤ 30 mL/min)

• evidence of current hypercalcemia or hypocalcemia (outside of 1.1 x the normal range)

• bone morphogenic proteins (BMP)-2 or BMP-7 at the time of definitive fracture fixation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35294
2	Research Site	Pomona	California	United States	91767
3	Research Site	Aurora	Colorado	United States	80012
4	Research Site	Denver	Colorado	United States	80204
5	Research Site	Indianapolis	Indiana	United States	46202
6	Research Site	Woodbury	Minnesota	United States	55125
7	Research Site	Saint Louis	Missouri	United States	63110
8	Research Site	Brooklyn	New York	United States	11220
9	Research Site	Rochester	New York	United States	14642
10	Research Site	Altoona	Pennsylvania	United States	16602
11	Research Site	Philadelphia	Pennsylvania	United States	19104
12	Research Site	State College	Pennsylvania	United States	16801
13	Research Site	Buenos Aires		Argentina	C1012AAR
14	Research Site	Buenos Aires		Argentina	C1419AHN
15	Research Site	Liverpool	New South Wales	Australia	2170
16	Research Site	Footscray	Victoria	Australia	3011
17	Research Site	Brugge		Belgium	8000
18	Research Site	Genk		Belgium	3600
19	Research Site	Leuven		Belgium	3000
20	Research Site	Liege		Belgium	4000
21	Research Site	Liège		Belgium	4020
22	Research Site	Blagoevgrad		Bulgaria	2700
23	Research Site	Pleven		Bulgaria	5800
24	Research Site	Plovdiv		Bulgaria	4002
25	Research Site	Red Deer	Alberta	Canada	T4N 6V7
26	Research Site	Cambridge	Ontario	Canada	N1R 3G2
27	Research Site	Guelph	Ontario	Canada	N1E 4J4
28	Research Site	Ottawa	Ontario	Canada	K1Y 4E9
29	Research Site	Toronto	Ontario	Canada	M5C 1R6
30	Research Site	Waterloo	Ontario	Canada	N2J 1C4
31	Research Site	Montreal	Quebec	Canada	H4J 1C5
32	Research Site	Quebec		Canada	G1J 1Z4
33	Research Site	Quebec		Canada	G1R 2J6
34	Research Site	Hvidovre		Denmark	2650
35	Research Site	København NV		Denmark	2400
36	Research Site	Viborg		Denmark	8800
37	Research Site	Ã…rhus C		Denmark	8000
38	Research Site	Tallinn		Estonia	11312
39	Research Site	Tartu		Estonia	50410
40	Research Site	Kuopio		Finland	70211
41	Research Site	Oulu		Finland	90220
42	Research Site	Turku		Finland	20520
43	Research Site	Aachen		Germany	52074
44	Research Site	Berlin		Germany	12200
45	Research Site	Muenchen		Germany	80336
46	Research Site	Muenster		Germany	48149
47	Research Site	Athens		Greece	12462
48	Research Site	Athens		Greece	14561
49	Research Site	Larissa		Greece	41110
50	Research Site	Patra		Greece	26500
51	Research Site	Thessaloniki		Greece	56429
52	Research Site	Hong Kong		Hong Kong
53	Research Site	New Territories		Hong Kong
54	Research Site	Budapest		Hungary	1081
55	Research Site	Miskolc		Hungary	3526
56	Research Site	Nyiregyhaza		Hungary	4400
57	Research Site	Szeged		Hungary	6725
58	Research Site	Hyderabad	Andhra Pradesh	India	500 063
59	Research Site	Bangalore	Karnataka	India	560 054
60	Research Site	Mangalore	Karnataka	India	575 002
61	Research Site	Nashik	Maharashtra	India	422 002
62	Research Site	Pune	Maharashtra	India	411 005
63	Research Site	Pune	Maharashtra	India	411 044
64	Research Site	Jaipur	Rajasthan	India	302 022
65	Research Site	Mangalore		India	575 001
66	Research Site	Nashik		India	422 009
67	Research Site	Firenze		Italy	50139
68	Research Site	Milano		Italy	20142
69	Research Site	Roma (RM)		Italy	00133
70	Research Site	Verona		Italy	37126
71	Research Site	Riga		Latvia	1005
72	Research Site	Valmiera		Latvia	4201
73	Research Site	Kaunas		Lithuania	44320
74	Research Site	Vilnius		Lithuania	04130
75	Research Site	Amsterdam		Netherlands	1061 AE
76	Research Site	Amsterdam		Netherlands	1091 AC
77	Research Site	Amsterdam		Netherlands	1105 AZ
78	Research Site	Haarlem		Netherlands	2035 RC
79	Research Site	Nieuwegein		Netherlands	3435 CM
80	Research Site	Christchurch		New Zealand	8022
81	Research Site	Kraków		Poland	31-826
82	Research Site	Lublin		Poland	20-718
83	Research Site	Warszawa		Poland	00-739
84	Research Site	Warszawa		Poland	03-242
85	Research Site	Celje		Slovenia	3000
86	Research Site	Izola		Slovenia	6310
87	Research Site	Jesenice		Slovenia	4270
88	Research Site	Sempeter pri Gorici		Slovenia	5290
89	Research Site	Linköping		Sweden	581 85
90	Research Site	Lund		Sweden	221 85
91	Research Site	Basel		Switzerland	4031
92	Research Site	Lausanne		Switzerland	1011
93	Research Site	Luzern		Switzerland	6000
94	Research Site	Zurich		Switzerland	8063
95	Research Site	Barnet		United Kingdom	EN5 3DJ
96	Research Site	Leeds		United Kingdom	LS1 3EX
97	Research Site	London		United Kingdom	E1 1BB
98	Research Site	Newcastle		United Kingdom	NE1 4LP
99	Research Site	Norwich		United Kingdom	NR4 7UY

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: NCT01081678
• Other Study ID Numbers: 20080394
• First Posted: Mar 5, 2010
• Last Update Posted: May 2, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Amgen: AMG 785; Proximal Femur; Fracture Healing; Hip Fracture
• Additional relevant MeSH terms: Fractures, Bone

Study Results

Participant Flow

Recruitment Details	This study was conducted at 63 centers in 22 countries in Eastern Europe, Western Europe, India, North America, Latin America, Australia, New Zealand and Hong Kong.
Pre-assignment Detail	Participants were randomized in a 2:3:3:3 ratio to 1 of 3 romosozumab treatment groups or placebo. Randomization followed operative fracture repair and was stratified by type of fracture, type of fixation device and age at entry. There were 7 randomization strata.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
Period Title: Overall Study
STARTED	89	60	93	90
Received Study Drug	87	60	89	89
Completed 24 Weeks of Study	73	50	72	68
COMPLETED	62	44	62	61
NOT COMPLETED	27	16	31	29

Baseline Characteristics

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg	Total
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Total of all reporting groups
Overall Participants	89	60	93	90	332
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.0 (8.6)	76.6 (10.3)	75.8 (10.1)	76.7 (9.5)	76.3 (9.5)
Age, Customized (Count of Participants)
< 65 years	10 11.2%	8 13.3%	17 18.3%	11 12.2%	46 13.9%
≥ 65 years	79 88.8%	52 86.7%	76 81.7%	79 87.8%	286 86.1%
Sex: Female, Male (Count of Participants)
Female	67 75.3%	42 70%	64 68.8%	55 61.1%	228 68.7%
Male	22 24.7%	18 30%	29 31.2%	35 38.9%	104 31.3%
Race/Ethnicity, Customized (Count of Participants)
White	77 86.5%	52 86.7%	81 87.1%	70 77.8%	280 84.3%
Black or African American	0 0%	0 0%	0 0%	1 1.1%	1 0.3%
Hispanic or Latino	0 0%	1 1.7%	1 1.1%	0 0%	2 0.6%
Asian	12 13.5%	7 11.7%	11 11.8%	19 21.1%	49 14.8%
Randomization Stratification (Count of Participants)
Intertrochanteric, SHS and 55-75 years	13 14.6%	9 15%	14 15.1%	14 15.6%	50 15.1%
Intertrochanteric, SHS and ≥ 76 years	16 18%	11 18.3%	16 17.2%	16 17.8%	59 17.8%
Intertrochanteric, IM Nail and 55-75 years	15 16.9%	10 16.7%	17 18.3%	16 17.8%	58 17.5%
Intertrochanteric, IM Nail and ≥ 76 years	33 37.1%	22 36.7%	34 36.6%	33 36.7%	122 36.7%
Displaced femoral neck and SHS	3 3.4%	2 3.3%	3 3.2%	3 3.3%	11 3.3%
Displaced femoral neck and cancellous screws	6 6.7%	4 6.7%	6 6.5%	5 5.6%	21 6.3%
Undisplaced femoral neck	3 3.4%	2 3.3%	3 3.2%	3 3.3%	11 3.3%

Outcome Measures

1. Primary Outcome

Title	Timed-Up-and-Go (TUG) Over Week 6 Through Week 20
Description	Functional healing was measured by the timed-up-and-go test (TUG) over Weeks 6 through 20. During this assessment, the clinician timed the participant while they stood up from a seated position in a chair, walked three meters, turned around, walked three meters back to the chair, and returned to the seated position. A TUG value of ten seconds or less was considered normal for a healthy elderly person. Higher TUG values after hip fracture have been shown to be a predictor of future falls. Least squares mean (LSM) estimates were based on a repeated measures model fitted with the log-transformed TUG values at weeks 2, 6, 12, 16, 20, 24, 36, 52 as the dependent variable and adjusted for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction and back-transformed using the exponential transformation.
Time Frame	Weeks 6, 12, 16, and 20

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least one dose of study drug with available data at each time point.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
Measure Participants	87	60	89	89
Week 6	54.1	41.0	47.2	53.3
Week 12	29.8	27.6	30.0	36.1
Week 16	26.2	23.3	26.9	31.8
Week 20	23.8	21.9	22.9	29.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romosozumab 70 mg, Romosozumab 140 mg, Romosozumab 210 mg
	Comments	The primary analysis was based on a test for linear trend in dose response at weeks 6, 12, 16, and 20. To account for multiple comparisons over time points, the primary analysis used a size α = 0.05 F-test with 4 degrees of freedom for the contrasts at Weeks 6, 12, 16, and 20.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1983
	Comments
	Method	F-test
	Comments	The p-value is based on F-test of multi-linear contrasts at Week 6 through Week 20.

2. Secondary Outcome

Title	Timed-Up-and-Go (TUG) at Each Visit
Description	During the timed-up-and-go test the clinician timed the participant while they stood up from a seated position in a chair, walked 3 meters, turned around, walked 3 meters back to the chair, and returned to a seated position. A TUG value of ≤ 10 seconds is considered normal for a healthy elderly person. LSMs were based on a repeated measures model adjusting for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction. Missing TUG values for participants still on study were imputed using the last observation carried forward (LOCF) when possible. If no observation could be carried forward, the maximum TUG value observed among all participants at a given visit was used. TUG values obtained after unplanned revision surgery were replaced by carrying forward the last available observed or imputed value prior to unplanned revision surgery.
Time Frame	Weeks 2, 6, 12, 16, 20, 24, 36, and 52

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug. LOCF imputation was used when possible, as described above.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
Measure Participants	87	60	89	89
Week 2	132.3	119.3	121.7	129.8
Week 6	92.4	69.5	80.3	86.7
Week 12	47.4	39.1	44.6	56.3
Week 16	43.1	31.6	39.7	50.1
Week 20	36.4	31.0	35.1	45.6
Week 24	33.3	28.9	31.7	40.9
Week 36	32.4	26.3	29.8	38.7
Week 52	28.7	22.8	28.8	36.3

3. Secondary Outcome

Title	Time to Radiographic Healing
Description	Time to radiographic healing is the time interval from the surgery date for the eligible hip fracture to the date of radiographic healing, defined as effacement of the fracture lines by newly formed bone along the cortices and within the trabecular bone on anteroposterior and lateral (or oblique) radiographs. Radiographic fracture healing was determined by a panel of independent reviewers blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
Measure Participants	87	60	89	89
Median (95% Confidence Interval) [weeks]	16.4	16.9	16.6	16.9

4. Secondary Outcome

Title	Radiographic Union Scale for Hip (RUSH) Score At Each Visit
Description	The radiographic Union Scale for Hip (RUSH) is a semiquantitative scoring assessment to assess hip fracture healing after surgical repair. The RUSH has 4 key domains based on radiographic parameters used by orthopedic surgeons and radiologists in routine clinical practice including cortical bridging (4 to 12 points), cortical fracture line disappearance (4 to 12 points), trabecular consolidation (1 to 3 points), and trabecular index disappearance of fracture line (1 to 3 points). The score has a minimum of 10 points (definitely not healed) and a maximum of 30 points (definitely healed).
Time Frame	Weeks 2, 6, 12, 16, 20, 24, 36, and 52

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug, with available data at baseline and at each time point. Missing RUSH scores for participants who were still on study were imputed using the using last observation carried forward procedure when possible.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
Measure Participants	87	60	89	89
Week 2	12.1 (3.3)	12.7 (3.5)	12.1 (3.4)	12.0 (3.1)
Week 6	18.1 (3.6)	18.0 (4.2)	18.4 (3.4)	18.3 (4.0)
Week 12	23.3 (4.6)	22.8 (4.8)	22.9 (4.8)	22.3 (5.3)
Week 16	25.6 (4.3)	25.7 (4.5)	25.5 (5.0)	25.5 (4.7)
Week 20	26.8 (4.1)	27.3 (4.1)	27.4 (4.0)	26.4 (4.6)
Week 24	27.8 (3.4)	27.8 (3.9)	28.3 (3.5)	27.3 (3.9)
Week 36	28.7 (2.6)	28.3 (3.6)	29.1 (2.1)	28.2 (3.5)
Week 52	29.4 (2.0)	28.5 (3.8)	29.6 (1.8)	28.7 (3.3)

5. Secondary Outcome

Title	Harris Hip Score At Each Visit
Description	The Harris Hip Score is a clinician-based outcome that assesses pain, function, deformity, and range of motion. The pain domain measures pain severity and its effect on activities and need for pain medication. The function domain consists of daily activities and gait. Deformity takes into account hip flexion, adduction, internal rotation, and extremity length discrepancy. Range of motion measures hip flexion, abduction, external and internal rotation, and adduction. The score ranges form 0-100 (best possible outcome) covering pain (0-44 points), function (0-47 points), absence of deformity (4 points), and range of motion (5 points). LSMs were based on a repeated measures model fitted with the Harris hip score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.
Time Frame	Weeks 2, 6, 12, 16, 20, 24, 36, and 52

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug with available data at each time point.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
Measure Participants	87	60	89	89
Week 2	46.6	47.7	47.3	46.5
Week 6	58.6	62.5	61.6	59.5
Week 12	71.2	70.9	71.7	69.6
Week 16	74.1	76.5	76.1	72.8
Week 20	76.2	80.2	80.5	77.5
Week 24	79.0	80.3	83.0	80.1
Week 36	80.3	82.0	86.8	83.6
Week 52	84.3	86.7	89.0	83.8

6. Secondary Outcome

Title	Hip Pain Score at Each Visit
Description	Hip pain was assessed using a visual analog scale (VAS). Participants were asked to rate their pain as a result of the hip fracture on a 100 mm vertical scale with 0 indicating no pain at all and 100 indicating the worst pain they could imagine. LSMs were based on a repeated measures model fitted with hip pain score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.
Time Frame	Weeks 2, 6, 12, 16, 20, 24, 36, and 52

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug with available data at each time point.

Arm/Group Title	Placebo	Romosozumab 70 mg	Romosozumab 140 mg	Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
Measure Participants	87	60	89	89
Week 2	34.3	33.1	40.3	43.0
Week 6	26.3	19.5	25.1	27.5
Week 12	19.4	17.8	17.5	23.7
Week 16	18.1	13.5	16.8	17.4
Week 20	15.8	9.2	14.0	15.0
Week 24	13.8	9.1	12.7	13.1
Week 36	14.3	10.9	11.6	10.2
Week 52	13.4	7.2	9.3	10.4

Adverse Events

Time Frame	52 weeks
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 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
Arm/Group Description	Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.		Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.		Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.		Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.
All Cause Mortality
	Placebo		Romosozumab 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Romosozumab 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/87 (28.7%)		9/60 (15%)		15/89 (16.9%)		26/89 (29.2%)
Blood and lymphatic system disorders
Anaemia	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Cardiac disorders
Acute coronary syndrome	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Acute myocardial infarction	1/87 (1.1%)		0/60 (0%)		1/89 (1.1%)		2/89 (2.2%)
Atrial fibrillation	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Atrioventricular block	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Cardiac arrest	0/87 (0%)		1/60 (1.7%)		1/89 (1.1%)		1/89 (1.1%)
Cardiac disorder	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Cardiac failure	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		1/89 (1.1%)
Cardiac failure congestive	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Cardio-respiratory arrest	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Haemorrhage coronary artery	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Myocardial infarction	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Gastrointestinal disorders
Abdominal pain	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Diarrhoea	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Duodenal ulcer haemorrhage	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Haematemesis	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Intestinal haemorrhage	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Pancreatitis acute	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
General disorders
Death	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Device dislocation	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Device failure	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Medical device complication	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		1/89 (1.1%)
Medical device discomfort	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		0/89 (0%)
Medical device pain	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Hepatobiliary disorders
Bile duct obstruction	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Cholecystitis acute	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Cholelithiasis	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		0/89 (0%)
Infections and infestations
Appendicitis	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Cellulitis	3/87 (3.4%)		0/60 (0%)		1/89 (1.1%)		1/89 (1.1%)
Clostridium difficile colitis	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Diverticulitis	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		1/89 (1.1%)
Escherichia urinary tract infection	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Gastroenteritis	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Gastroenteritis viral	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Infection	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		0/89 (0%)
Lower respiratory tract infection	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		1/89 (1.1%)
Lung infection	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Pneumonia	1/87 (1.1%)		0/60 (0%)		1/89 (1.1%)		2/89 (2.2%)
Pneumonia bacterial	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		1/89 (1.1%)
Post procedural infection	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Postoperative wound infection	0/87 (0%)		0/60 (0%)		0/89 (0%)		3/89 (3.4%)
Respiratory tract infection	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		0/89 (0%)
Urinary tract infection	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Wound infection	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Injury, poisoning and procedural complications
Bone fissure	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Femoral neck fracture	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Femur fracture	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Hip fracture	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		2/89 (2.2%)
Pelvic fracture	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Post procedural complication	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Tibia fracture	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Urinary retention postoperative	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Investigations
Hepatic enzyme increased	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Metabolism and nutrition disorders
Dehydration	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Hypoglycaemia	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Musculoskeletal and connective tissue disorders
Fracture nonunion	1/87 (1.1%)		1/60 (1.7%)		0/89 (0%)		0/89 (0%)
Musculoskeletal chest pain	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Osteoarthritis	2/87 (2.3%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Pseudarthrosis	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Pancreatic neoplasm	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Plasma cell myeloma	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Squamous cell carcinoma of the vagina	0/87 (0%)		0/60 (0%)		1/89 (1.1%)		0/89 (0%)
Nervous system disorders
Cerebellar artery thrombosis	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Cerebrovascular accident	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		1/89 (1.1%)
Dementia Alzheimer's type	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Ischaemic stroke	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Myasthenia gravis	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Transient ischaemic attack	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Psychiatric disorders
Depression	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Renal and urinary disorders
Haematuria	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Renal failure acute	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Urinary retention	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Reproductive system and breast disorders
Prostatomegaly	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		2/89 (2.2%)
Acute respiratory failure	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Chronic obstructive pulmonary disease	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		0/89 (0%)
Respiratory failure	0/87 (0%)		1/60 (1.7%)		0/89 (0%)		0/89 (0%)
Skin and subcutaneous tissue disorders
Acute generalised exanthematous pustulosis	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Surgical and medical procedures
Nail operation	0/87 (0%)		0/60 (0%)		0/89 (0%)		1/89 (1.1%)
Vascular disorders
Deep vein thrombosis	1/87 (1.1%)		0/60 (0%)		0/89 (0%)		0/89 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Romosozumab 70 mg		Romosozumab 140 mg		Romosozumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/87 (35.6%)		24/60 (40%)		30/89 (33.7%)		26/89 (29.2%)
Gastrointestinal disorders
Constipation	11/87 (12.6%)		6/60 (10%)		9/89 (10.1%)		6/89 (6.7%)
Diarrhoea	8/87 (9.2%)		2/60 (3.3%)		2/89 (2.2%)		4/89 (4.5%)
Nausea	7/87 (8%)		4/60 (6.7%)		7/89 (7.9%)		2/89 (2.2%)
General disorders
Pyrexia	0/87 (0%)		3/60 (5%)		2/89 (2.2%)		3/89 (3.4%)
Infections and infestations
Urinary tract infection	8/87 (9.2%)		4/60 (6.7%)		8/89 (9%)		4/89 (4.5%)
Injury, poisoning and procedural complications
Contusion	1/87 (1.1%)		3/60 (5%)		0/89 (0%)		0/89 (0%)
Procedural pain	5/87 (5.7%)		1/60 (1.7%)		5/89 (5.6%)		2/89 (2.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/87 (2.3%)		3/60 (5%)		6/89 (6.7%)		5/89 (5.6%)
Back pain	0/87 (0%)		7/60 (11.7%)		5/89 (5.6%)		4/89 (4.5%)
Osteoarthritis	1/87 (1.1%)		3/60 (5%)		5/89 (5.6%)		2/89 (2.2%)
Pain in extremity	5/87 (5.7%)		0/60 (0%)		0/89 (0%)		2/89 (2.2%)
Vascular disorders
Hypertension	3/87 (3.4%)		4/60 (6.7%)		5/89 (5.6%)		4/89 (4.5%)

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.