Postmenopausal OsteoporosisPhase 3FRAMENCT01575834
Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis
A Phase 3 study testing Romosozumab and Denosumab in people with Postmenopausal Osteoporosis, run by Amgen at 218 sites in 24 countries.
Trial summary
The purpose of this study is to determine if treatment with romosozumab is effective in preventing fractures in women with postmenopausal osteoporosis Read more about this study
- Who is it for?
- Ages 55 to 90 years, women only
- Conditions the study is for
- Postmenopausal Osteoporosis
- What is being tested?
- Romosozumab and Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7,180 participants
- Where
- 218 sitesin 24 countries
- Study dates
- 15 Mar 2012to 28 Dec 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal women with osteoporosis, defined as low bone mineral density (BMD T-score at the total hip or femoral neck of ≤ -2.50)
Who cannot join
- BMD T-score of ≤ -3.50 at the total hip or femoral neck
- History of hip fracture
- Any severe or more than 2 moderate vertebral fractures, as assessed by the central imaging based on lateral spine x-rays
- Use of agents affecting bone metabolism
- History of metabolic or bone disease (except osteoporosis)
- Vitamin D insufficiency (vitamin D repletion and rescreening is permitted)
Show all 9Show fewer
- Current hyper- or hypocalcemia
- Current, uncontrolled hyper- or hypothyroidism
- Current, uncontrolled hyper- or hypoparathyroidism
Trial locations and contacts
218 sites in 24 countries.
218 sites in 24 countries
Japan56 sites
Research Site
Akashi-shi, Hyōgo, 674-0051
Research Site
Anjyo-shi, Aichi-ken, 446-0063
Research Site
Atugi-shi, Kanagawa, 243-0122
Research Site
Bungoono-shi, Oita Prefecture, 879-7125
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Chiisagata-gun, Nagano, 386-0603
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Chitose-shi, Hokkaido, 066-0062
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Fujimi-shi, Saitama, 354-0021
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Fujinomiya-shi, Shizuoka, 418-0026
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Fukui-shi, Fukui, 910-0005
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Fukui-shi, Fukui, 910-0067
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Fukui-shi, Fukui, 918-8057
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Fukui-shi, Fukui, 918-8236
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Fukuoka, Fukuoka, 814-0111
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Fukutsu-shi, Fukuoka, 811-3217
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Hachioji-shi, Tokyo, 192-0046
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Hiroshima, Hiroshima, 733-0032
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Ishikari-shi, Hokkaido, 061-3203
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Kako-gun, Hyōgo, 675-1115
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Kikugawa-shi, Shizuoka, 439-0012
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Kirishima-shi, Kagoshima-ken, 899-5102
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Kitakyushu-shi, Fukuoka, 806-0026
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Kiyose-shi, Tokyo, 204-0021
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Kofu, Yamanashi, 400-0831
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Kumamoto, Kumamoto, 860-0066
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Kurume-shi, Fukuoka, 830-0053
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Kurume-shi, Fukuoka, 839-0832
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Matsue, Shimane, 699-0293
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Matsumoto-shi, Nagano, 390-1401
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Matsumoto-shi, Nagano, 390-8601
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Minamikyusyu-shi, Kagoshima-ken, 897-0215
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Minato-ku, Tokyo, 108-0075
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Morioka, Iwate, 020-0015
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Osaka, Osaka, 559-0011
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Ōta-ku, Tokyo, 143-0015
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Saga, Saga-ken, 840-0027
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Sagamihara-shi, Kanagawa, 252-5225
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Sendai, Miyagi, 981-3213
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Setagaya-ku, Tokyo, 157-0073
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Shinagawa-ku, Tokyo, 140-0001
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Shinagawa-ku, Tokyo, 140-0014
Research Site
Suginami-ku, Tokyo, 166-0001
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Suginami-ku, Tokyo, 166-0003
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Sunagawa-shi, Hokkaido, 073-0196
Research Site
Takamatsu, Kagawa-ken, 760-8538
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Takatsuki-shi, Osaka, 569-1123
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Tokushima, Tokushima, 770-8503
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Toride-shi, Ibaraki, 302-0022
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Toshima-ku, Tokyo, 171-0033
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Ueda-shi, Nagano, 386-0151
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Ueda-shi, Nagano, 386-0405
Research Site
Urayasu-shi, Chiba, 279-0004
Research Site
Yokohama, Kanagawa, 223-0059
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Yokohama, Kanagawa, 223-0062
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Yokohama, Kanagawa, 227-0064
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Yokohama, Kanagawa, 231-0023
Research Site
Yokohama, Kanagawa, 231-0861
United States25 sites
Research Site
Albuquerque, New Mexico, 87106
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Asheville, North Carolina, 28803
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Bethesda, Maryland, 20817
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Boston, Massachusetts, 02114
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Cincinnati, Ohio, 45236
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Denton, Texas, 76210-8625
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Detroit, Michigan, 48236
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Duncansville, Pennsylvania, 16635
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Fargo, North Dakota, 58104
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Gainesville, Georgia, 30501
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Laguna Hills, California, 92653
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Lakewood, Colorado, 80227
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Leesburg, Florida, 34748
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Los Angeles, California, 90057
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Madison, Wisconsin, 53705
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Mayfield, Ohio, 44143
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New Orleans, Louisiana, 70121
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Palm Harbor, Florida, 34684
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Plantation, Florida, 33324
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Richmond, Virginia, 23294
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Sacramento, California, 95817
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Santa Maria, California, 93454
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Tampa, Florida, 33614
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Tucson, Arizona, 85704
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Walnut Creek, California, 94598
Germany15 sites
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Berlin, 12200
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Bochum, 44787
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Dresden, 01067
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Dresden, 01307
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Frankfurt am Main, 60313
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Frankfurt am Main, 60528
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Görlitz, 02826
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Hamburg, 20354
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Hanover, 30167
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Heinsberg, 52525
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Hellersdorf, 12627
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Leipzig, 04103
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Magdeburg, 39120
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Marburg, 35043
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Schkeuditz, 04435
Czechia12 sites
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Brno, 602 00
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České Budějovice, 370 87
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Havlíčkův Brod, 580 22
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Klatovy, 339 38
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Ostrava-Trebovice, 722 00
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Pardubice, 530 02
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Pilsen, 305 99
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Prague, 128 50
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Prague, 130 00
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Praha 11 - Chodov, 148 00
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Uherské Hradiště, 686 01
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Zlín, 760 01
Hungary9 sites
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Békéscsaba, 5600
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Budapest, 1027
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Budapest, 1036
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Budapest, 1083
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Debrecen, 4032
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Győr, 9023
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Hévíz, 8380
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Szeged, 6720
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Zalaegerszeg, 8900
Argentina8 sites
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Buenos Aires, 1425
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Buenos Aires, C1425ACG
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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1012AAR
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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1015ABO
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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1128AAF
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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1430CKE
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Córdoba, Córdoba Province, X5000BNB
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Mar del Plata, Buenos Aires, B7600DHK
Australia8 sites
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Footscray, Victoria, 3011
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Geelong, Victoria, 3220
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Heidelberg West, Victoria, 3081
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Herston, Queensland, 4029
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Keswick, South Australia, 5035
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Maroubra, New South Wales, 2035
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Nedlands, Western Australia, 6009
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St Leonards, New South Wales, 2065
Belgium7 sites
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Brussels, 1000
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Genk, 3600
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Ghent, 9000
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Leuven, 3000
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Liège, 4020
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Lommel, 3920
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Yvoir, 5530
Colombia7 sites
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Barranquilla, Atlántico, 08001000
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Bogota, Cundinamarca, 11001000
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Bogota, Cundinamarca, 110221
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Bogota, Cundinamarca, 1
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Bogota, Cundinamarca
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Bogotá, 11001000
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Medellín, Antioquia, 050021
Denmark7 sites
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Aalborg, 9000
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Århus C, 8000
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Ballerup Municipality, 2750
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Glostrup Municipality, 2600
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Hvidovre, 2650
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Odense, 5000
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Vejle, 7100
Poland7 sites
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Dabrowka Dopiewo, 62-069
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Elblag, 82-300
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Krakow, 30-510
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Lodz, 90-368
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Świdnik, 21-040
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Warsaw, 02-341
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Wroclaw, 51-124
United Kingdom7 sites
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Chorley, PR7 7NA
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Glasgow, G20 0SP
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Liverpool, L22 0LG
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London, DA14 6LT
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Manchester, M15 6SX
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Northwood, HA6 2RN
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Reading, RG2 0TF
Canada6 sites
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Calgary, Alberta, T2N 4Z6
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Hamilton, Ontario, L8N 1Y2
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Lachine, Quebec, H8S 2E4
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Oakville, Ontario, L6M 1M1
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Québec, Quebec, G1V 3M7
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Vancouver, British Columbia, V5Z 4E1
India6 sites
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Bangalore, Karnataka, 560 054
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Chennai, Tamil Nadu, 600 020
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Jaipur, Rajasthan, 302 019
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Mumbai, Maharashtra, 400 012
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Pune, Maharashtra, 411 005
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Vellore, Tamil Nadu, 632 004
Switzerland6 sites
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Bern, 3010
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Fribourg, 1708
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Geneva, 1211
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Lausanne, 1011
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Zurich, 8063
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Zurich, 8091
Brazil5 sites
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Curitiba, Paraná, 80030-110
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São Paulo, São Paulo, 04063-001
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São Paulo, 04266-010
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São Paulo, 05403-000
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São Paulo, 05437-010
Lithuania5 sites
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Kaunas, 49287
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Kaunas, 49456
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Klaipėda, 94231
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Vilnius, 09310
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Vilnius, 10323
Spain5 sites
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Barcelona, Catalonia, 08041
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Madrid, 28009
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Madrid, 28041
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Pozuelo de Alarcón, Madrid, 28223
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Valencia, Valencia, 46026
Dominican Republic3 sites
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Santo Domingo, Nacional, 10124
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Santo Domingo, Nacional, 10514
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Santo Domingo, 10605
Estonia3 sites
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Pärnu, 80013
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Tallinn, 10128
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Tartu, 50410
Latvia3 sites
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Liepāja, 3401
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Riga, 1012
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Riga, 1038
Mexico3 sites
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Ciudad Obregón, Sonora, 85000
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Mexico City, Mexico City, 06100
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Monterrey, Nuevo León, 64460
Romania3 sites
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Bucharest, 011172
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Bucharest, 020125
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Timișoara, 300736
New Zealand2 sites
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Christchurch, 8022
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Grafton, Auckland, 1023
About this study
Official title: A Multicenter, International, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis
The purpose of this study is to determine if treatment with romosozumab is effective in preventing fractures in women with postmenopausal osteoporosis
- Conditions
- Postmenopausal Osteoporosis
- Being tested
- Romosozumab, Placebo, Denosumab
- Keywords
- Osteoporosis, Osteoporosis-Postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases
- Medical subject headings
- Osteoporosis, Postmenopausal, Osteoporosis, Bone Diseases, Metabolic, Bone Diseases, Musculoskeletal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomosozumabDrug
Also called AMG 785, EVENITY™
Administered by subcutaneous injection once a month (QM)
PlaceboDrug
Administered by subcutaneous injection once a month (QM)
DenosumabDrug
Also called Prolia®
Administered by subcutaneous injection once every 6 months (Q6M)
| Study group | Role | What they receive |
|---|---|---|
| Romosozumab | Experimental | Participants received 210 mg romosozumab subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months. Receives: Drug: Romosozumab; Drug: Denosumab |
| Placebo | Placebo comparator | Participants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months. Receives: Drug: Placebo; Drug: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With New Vertebral Fracture Through Month 12
New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method.
The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale:
- Grade 0 (Normal) = no fracture;
- Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior);
- Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height;
- Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height.
Measured: 12 Months
Percentage of Participants With New Vertebral Fracture Through Month 24
New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method.
The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale:
- Grade 0 (Normal) = no fracture;
- Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior);
- Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height;
- Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height.
Measured: 24 months
Secondary outcomes (20)
Percentage of Participants With a Clinical Fracture Through Month 12
Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.
Measured: 12 Months
Percentage of Participants With a Nonvertebral Fracture Through Month 12
A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.
Measured: 12 Months
Percentage of Participants With a Nonvertebral Fracture Through Month 24
A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date as recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.
Measured: 24 Months
Percentage of Participants With a Clinical Fracture Through Month 24
Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.
Measured: 24 Months
Percentage of Participants With a Major Nonvertebral Fracture Through Month 12
A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip.
Measured: 12 Months
Percentage of Participants With a Major Nonvertebral Fracture Through Month 24
A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip.
Measured: 24 Months
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 12
A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4.
Measured: 12 Months
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24
A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4.
Measured: 24 Months
Percentage of Participants With a Hip Fracture Through Month 12
Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.
Measured: 12 Months
Percentage of Participants With a Hip Fracture Through Month 24
Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.
Measured: 24 Months
Percentage of Participants With a Major Osteoporotic Fracture Through Month 12
Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded.
Measured: 12 Months
Percentage of Participants With a Major Osteoporotic Fracture Through Month 24
Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded.
Measured: 24 Months
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 12
A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit.
Measured: 12 Months
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24
A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit.
Measured: 24 Months
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Measured: Baseline and Month 12
Percent Change From Baseline In Bone Mineral Density at the Lumbar Spine at Month 24
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Measured: Baseline and Month 24
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 12
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Measured: Baseline and Month 12
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Measured: Baseline and Month 24
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 12
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Measured: Baseline and Month 12
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 24
Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Measured: Baseline and Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study start15 Mar 2012
- Primary completion14 Dec 2015
- Study completion28 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7,180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01575834
- Sponsor's protocol ID
- 20070337
- Other IDs
- 2011-001456-11
- Acronym
- FRAME
- Status last verified
- Aug 2024
- First submitted
- 4 Apr 2012
- Last updated
- 28 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Oct 20;375(16):1532-1543. doi: 10.1056/NEJMoa1607948. Epub 2016 Sep 18.
PubMed 27641143Cosman F, Crittenden DB, Ferrari S, Khan A, Lane NE, Lippuner K, Matsumoto T, Milmont CE, Libanati C, Grauer A. FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab. J Bone Miner Res. 2018 Jul;33(7):1219-1226. doi: 10.1002/jbmr.3427. Epub 2018 May 17.
PubMed 29573473Chavassieux P, Chapurlat R, Portero-Muzy N, Roux JP, Garcia P, Brown JP, Libanati C, Boyce RW, Wang A, Grauer A. Bone-Forming and Antiresorptive Effects of Romosozumab in Postmenopausal Women With Osteoporosis: Bone Histomorphometry and Microcomputed Tomography Analysis After 2 and 12 Months of Treatment. J Bone Miner Res. 2019 Sep;34(9):1597-1608. doi: 10.1002/jbmr.3735. Epub 2019 Jun 24.
PubMed 31233639Cosman F, Crittenden DB, Ferrari S, Lewiecki EM, Jaller-Raad J, Zerbini C, Milmont CE, Meisner PD, Libanati C, Grauer A. Romosozumab FRAME Study: A Post Hoc Analysis of the Role of Regional Background Fracture Risk on Nonvertebral Fracture Outcome. J Bone Miner Res. 2018 Aug;33(8):1407-1416. doi: 10.1002/jbmr.3439. Epub 2018 May 11.
PubMed 29750828Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, Gielen E, Milmont CE, Libanati C, Grauer A. One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study. J Bone Miner Res. 2019 Mar;34(3):419-428. doi: 10.1002/jbmr.3622. Epub 2018 Dec 3.
PubMed 30508316Miyauchi A, Dinavahi RV, Crittenden DB, Yang W, Maddox JC, Hamaya E, Nakamura Y, Libanati C, Grauer A, Shimauchi J. Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension. Arch Osteoporos. 2019 Jun 5;14(1):59. doi: 10.1007/s11657-019-0608-z.
PubMed 31168657Miyauchi A, Hamaya E, Yang W, Nishi K, Libanati C, Tolman C, Shimauchi J. Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial. J Bone Miner Metab. 2021 Mar;39(2):278-288. doi: 10.1007/s00774-020-01147-5. Epub 2020 Oct 15.
PubMed 33057807McCloskey EV, Johansson H, Harvey NC, Lorentzon M, Shi Y, Kanis JA. Romosozumab efficacy on fracture outcomes is greater in patients at high baseline fracture risk: a post hoc analysis of the first year of the frame study. Osteoporos Int. 2021 Aug;32(8):1601-1608. doi: 10.1007/s00198-020-05815-0. Epub 2021 Feb 3.
PubMed 33537844Eriksen EF, Chapurlat R, Boyce RW, Shi Y, Brown JP, Horlait S, Betah D, Libanati C, Chavassieux P. Modeling-Based Bone Formation After 2 Months of Romosozumab Treatment: Results From the FRAME Clinical Trial. J Bone Miner Res. 2022 Jan;37(1):36-40. doi: 10.1002/jbmr.4457. Epub 2021 Nov 19.
PubMed 34633116Miller PD, Adachi JD, Albergaria BH, Cheung AM, Chines AA, Gielen E, Langdahl BL, Miyauchi A, Oates M, Reid IR, Santiago NR, Vanderkelen M, Wang Z, Yu Z. Efficacy and Safety of Romosozumab Among Postmenopausal Women With Osteoporosis and Mild-to-Moderate Chronic Kidney Disease. J Bone Miner Res. 2022 Aug;37(8):1437-1445. doi: 10.1002/jbmr.4563. Epub 2022 May 20.
PubMed 35466448Takada J, Dinavahi R, Miyauchi A, Hamaya E, Hirama T, Libanati C, Nakamura Y, Milmont CE, Grauer A. Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial. J Bone Miner Metab. 2020 May;38(3):310-315. doi: 10.1007/s00774-019-01057-1. Epub 2019 Nov 9.
PubMed 31707465Miyauchi A, Hamaya E, Nishi K, Tolman C, Shimauchi J. Efficacy and safety of romosozumab among Japanese postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. J Bone Miner Metab. 2022 Jul;40(4):677-687. doi: 10.1007/s00774-022-01332-8. Epub 2022 May 31.
PubMed 35639174Eriksen EF, Boyce RW, Shi Y, Brown JP, Betah D, Libanati C, Oates M, Chapurlat R, Chavassieux P. Reconstruction of remodeling units reveals positive effects after 2 and 12 months of romosozumab treatment. J Bone Miner Res. 2024 Jul 23;39(6):729-736. doi: 10.1093/jbmr/zjae055.
PubMed 38640512Lane NE, Betah D, Deignan C, Oates M, Wang Z, Timoshanko J, Khan AA, Binkley N. Effect of Romosozumab Treatment in Postmenopausal Women With Osteoporosis and Knee Osteoarthritis: Results From a Substudy of a Phase 3 Clinical Trial. ACR Open Rheumatol. 2024 Jan;6(1):43-51. doi: 10.1002/acr2.11619. Epub 2023 Nov 20.
PubMed 37985218McClung MR, Betah D, Deignan C, Shi Y, Timoshanko J, Cosman F. Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk. Endocr Pract. 2023 Sep;29(9):716-722. doi: 10.1016/j.eprac.2023.06.011. Epub 2023 Jul 4.
PubMed 37406858
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, International, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis
- ClinicalTrials.gov ID
- NCT01575834
- Acronym / sponsor ID
- FRAME / 20070337
- Conditions
- Postmenopausal Osteoporosis
- Keywords
- Osteoporosis, Osteoporosis-Postmenopausal, Bone Diseases-Metabolic, Bone Diseases, Musculoskeletal Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7,180 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 15 Mar 2012 (actual)
- Primary completion
- 14 Dec 2015 (actual)
- Study completion
- 28 Dec 2016 (actual)
- First posted
- 12 Apr 2012 (estimated)
- Results
- Posted 8 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if treatment with romosozumab is effective in preventing fractures in women with postmenopausal osteoporosis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Romosozumab | Experimental | Drug: Romosozumab, Drug: DenosumabParticipants received 210 mg romosozumab subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: DenosumabParticipants received placebo subcutaneous injections once a month for 12 months, followed by 60 mg denosumab subcutaneously once every 6 months for 24 months. |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Postmenopausal women with osteoporosis, defined as low bone mineral density (BMD T-score at the total hip or femoral neck of ≤ -2.50)
Key exclusion criteria (9 listed)
- BMD T-score of ≤ -3.50 at the total hip or femoral neck
- History of hip fracture
- Any severe or more than 2 moderate vertebral fractures, as assessed by the central imaging based on lateral spine x-rays
- Use of agents affecting bone metabolism
- History of metabolic or bone disease (except osteoporosis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RomosozumabAlso: AMG 785, EVENITY™Administered by subcutaneous injection once a month (QM) | Drug | Romosozumab |
| PlaceboAdministered by subcutaneous injection once a month (QM) | Drug | Placebo |
| DenosumabAlso: Prolia®Administered by subcutaneous injection once every 6 months (Q6M) | Drug | Placebo, Romosozumab |
Primary outcome
Percentage of Participants With New Vertebral Fracture Through Month 12
Time frame: 12 Months
New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height.
Percentage of Participants With New Vertebral Fracture Through Month 24
Time frame: 24 months
New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height.
20 secondary outcomes
Percentage of Participants With a Clinical Fracture Through Month 12
Time frame: 12 Months
Percentage of Participants With a Nonvertebral Fracture Through Month 12
Time frame: 12 Months
Percentage of Participants With a Nonvertebral Fracture Through Month 24
Time frame: 24 Months
Percentage of Participants With a Clinical Fracture Through Month 24
Time frame: 24 Months
Percentage of Participants With a Major Nonvertebral Fracture Through Month 12
Time frame: 12 Months
Percentage of Participants With a Major Nonvertebral Fracture Through Month 24
Time frame: 24 Months
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 12
Time frame: 12 Months
Percentage of Participants With a New or Worsening Vertebral Fracture Through Month 24
Time frame: 24 Months
Percentage of Participants With a Hip Fracture Through Month 12
Time frame: 12 Months
Percentage of Participants With a Hip Fracture Through Month 24
Time frame: 24 Months
Percentage of Participants With a Major Osteoporotic Fracture Through Month 12
Time frame: 12 Months
Percentage of Participants With a Major Osteoporotic Fracture Through Month 24
Time frame: 24 Months
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 12
Time frame: 12 Months
Percentage of Participants With Multiple New or Worsening Vertebral Fractures Through Month 24
Time frame: 24 Months
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12
Time frame: Baseline and Month 12
Percent Change From Baseline In Bone Mineral Density at the Lumbar Spine at Month 24
Time frame: Baseline and Month 24
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 12
Time frame: Baseline and Month 12
Percent Change From Baseline in Bone Mineral Density of the Total Hip at Month 24
Time frame: Baseline and Month 24
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 12
Time frame: Baseline and Month 12
Percent Change From Baseline in Bone Mineral Density of the Femoral Neck at Month 24
Time frame: Baseline and Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27641143Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Oct 20;375(16):1532-1543. doi: 10.1056/NEJMoa1607948. Epub 2016 Sep 18.
- Background: PubMed 29573473Cosman F, Crittenden DB, Ferrari S, Khan A, Lane NE, Lippuner K, Matsumoto T, Milmont CE, Libanati C, Grauer A. FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab. J Bone Miner Res. 2018 Jul;33(7):1219-1226. doi: 10.1002/jbmr.3427. Epub 2018 May 17.
- Background: PubMed 31233639Chavassieux P, Chapurlat R, Portero-Muzy N, Roux JP, Garcia P, Brown JP, Libanati C, Boyce RW, Wang A, Grauer A. Bone-Forming and Antiresorptive Effects of Romosozumab in Postmenopausal Women With Osteoporosis: Bone Histomorphometry and Microcomputed Tomography Analysis After 2 and 12 Months of Treatment. J Bone Miner Res. 2019 Sep;34(9):1597-1608. doi: 10.1002/jbmr.3735. Epub 2019 Jun 24.
- Background: PubMed 29750828Cosman F, Crittenden DB, Ferrari S, Lewiecki EM, Jaller-Raad J, Zerbini C, Milmont CE, Meisner PD, Libanati C, Grauer A. Romosozumab FRAME Study: A Post Hoc Analysis of the Role of Regional Background Fracture Risk on Nonvertebral Fracture Outcome. J Bone Miner Res. 2018 Aug;33(8):1407-1416. doi: 10.1002/jbmr.3439. Epub 2018 May 11.
- Background: PubMed 30508316Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, Gielen E, Milmont CE, Libanati C, Grauer A. One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study. J Bone Miner Res. 2019 Mar;34(3):419-428. doi: 10.1002/jbmr.3622. Epub 2018 Dec 3.
- Background: PubMed 31168657Miyauchi A, Dinavahi RV, Crittenden DB, Yang W, Maddox JC, Hamaya E, Nakamura Y, Libanati C, Grauer A, Shimauchi J. Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension. Arch Osteoporos. 2019 Jun 5;14(1):59. doi: 10.1007/s11657-019-0608-z.
- Background: PubMed 33057807Miyauchi A, Hamaya E, Yang W, Nishi K, Libanati C, Tolman C, Shimauchi J. Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial. J Bone Miner Metab. 2021 Mar;39(2):278-288. doi: 10.1007/s00774-020-01147-5. Epub 2020 Oct 15.
- Background: PubMed 33537844McCloskey EV, Johansson H, Harvey NC, Lorentzon M, Shi Y, Kanis JA. Romosozumab efficacy on fracture outcomes is greater in patients at high baseline fracture risk: a post hoc analysis of the first year of the frame study. Osteoporos Int. 2021 Aug;32(8):1601-1608. doi: 10.1007/s00198-020-05815-0. Epub 2021 Feb 3.
- Background: PubMed 34633116Eriksen EF, Chapurlat R, Boyce RW, Shi Y, Brown JP, Horlait S, Betah D, Libanati C, Chavassieux P. Modeling-Based Bone Formation After 2 Months of Romosozumab Treatment: Results From the FRAME Clinical Trial. J Bone Miner Res. 2022 Jan;37(1):36-40. doi: 10.1002/jbmr.4457. Epub 2021 Nov 19.
- Background: PubMed 35466448Miller PD, Adachi JD, Albergaria BH, Cheung AM, Chines AA, Gielen E, Langdahl BL, Miyauchi A, Oates M, Reid IR, Santiago NR, Vanderkelen M, Wang Z, Yu Z. Efficacy and Safety of Romosozumab Among Postmenopausal Women With Osteoporosis and Mild-to-Moderate Chronic Kidney Disease. J Bone Miner Res. 2022 Aug;37(8):1437-1445. doi: 10.1002/jbmr.4563. Epub 2022 May 20.
- Background: PubMed 31707465Takada J, Dinavahi R, Miyauchi A, Hamaya E, Hirama T, Libanati C, Nakamura Y, Milmont CE, Grauer A. Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial. J Bone Miner Metab. 2020 May;38(3):310-315. doi: 10.1007/s00774-019-01057-1. Epub 2019 Nov 9.
- Background: PubMed 35639174Miyauchi A, Hamaya E, Nishi K, Tolman C, Shimauchi J. Efficacy and safety of romosozumab among Japanese postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. J Bone Miner Metab. 2022 Jul;40(4):677-687. doi: 10.1007/s00774-022-01332-8. Epub 2022 May 31.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
218 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Romosozumab and Denosumab in people with Postmenopausal Osteoporosis, run by Amgen at 218 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 218 sites in Japan, United States, Germany, Czechia, Hungary and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With New Vertebral Fracture Through Month 12 (time frame: 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01575834, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.