Premenopausal Idiopathic OsteoporosisPhase 2NCT04800367
Romosozumab/Denosumab Study for Premenopausal IOP
A Phase 2 study testing Romosozumab Prefilled Syringe [Evenity] and Denosumab 60 MG/ML Prefilled Syringe [Prolia] in people with Premenopausal Idiopathic Osteoporosis, run by Columbia University at 1 site in United States.
Trial summary
The overarching goal of the research program is to define optimal treatment for premenopausal women with clinically significant fracture syndromes that require medical therapy. The investigators hypothesize that romosozumab will be associated with improvements in bone mass and microarchitecture in premenopausal women… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Premenopausal Idiopathic Osteoporosis
- What is being tested?
- Romosozumab Prefilled Syringe [Evenity] and Denosumab 60 MG/ML Prefilled Syringe [Prolia]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2021to Mar 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Premenopausal women, aged 18-48, with regular menses and no historical or biochemical secondary cause of osteoporosis; the lower age limit is to ensure epiphyses are fused, the upper to make it less likely that women will enter menopause during the study. All subjects under age 25 will be screened (bone age radiograph) prior to enrollment to rule out open epiphyses.
- Documented adult fractures judged to be low-trauma (equivalent to a fall from a standing height or less) and T-score or Z-score ≤ -1.5 at the LS, TH or FN.
- Must agree to use highly effective contraception throughout the period of study drug administration.
- Highly effective contraception includes methods considered by the CDC to be >99% effective (e.g. vasectomized partner, tubal ligation, hysterectomy, IUD) as well as a combination of barrier method (condoms) with hormonal contraception considered to be > 90% effective (oral contraceptive pill, patch or ring). Systemic progestin only methods (oral or implanted) are not included due to their effect on systemic estrogen levels and thus potential effects on bone health in this premenopausal population.
Who cannot join
- Any cardiovascular disease: history of myocardial infarction (MI) or stroke. Normal electrocardiogram (ECG) or ECG with no clinically significant abnormality is required at study entry.
- Conditions requiring chronic anticoagulation (coumadin, heparins)
- Early follicular phase serum FSH>20 mIU/ml (to exclude perimenopausal women)
- Disorders of mineral metabolism: primary/secondary hyperparathyroidism, osteomalacia (including that associated with a diagnosis of hypophosphatasia), vitamin D deficiency
- Suspicion of osteomalacia (elevated alkaline phosphatase, bone pain exacerbated by weight bearing, bone tenderness)
- Vitamin D deficiency (serum 25-OHD<30ng/ml). Women with levels of 10-29 ng/ml will be eligible after treatment with vitamin D has resulted in levels ≥30 ng/ml.
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- Hypocalcemia
- Hypercalciuria: urinary calcium excretion over 300 mg/g Cr that can not be effectively lowered with medical management (reduced calcium intake, thiazide diuretics). As in our prior studies, prevalent nephrolithiasis in the absence of pretreatment hypercalciuria is not an exclusion.
- Current pregnancy or lactation
- Highly effective contraception is required, pregnancy testing is performed at each visit
- Current active eating disorder, hypothalamic or exercise induced amenorrhea. Patients with past history of these disorders, resolved > 1 year ago, are eligible to participate. The Eating Aptitude Test -Questionnaire is given to identify women with subclinical eating disorders
- Current malignancy
- Endocrinopathy: new onset untreated hyperthyroidism/hypothyroidism, Cushing's syndrome, prolactinoma
- Renal insufficiency (eGFR below 60 ml/min)
- Liver disease (AST, ALT, bilirubin, total alkaline phosphatase activity above upper normal limit)
- Intestinal malabsorption disorders including but not limited to pancreatic insufficiency, active Crohn Disease or untreated celiac disease.
- History/current GCs, anticonvulsants, anticoagulants, methotrexate, GnRH agonists to suppress menstruation
- Oral glucocorticoid dose equivalent >5 mg prednisone for >3 months.
- Current use of specific anticonvulsants (carbamazepine, phenytoin, phenobarbital), methotrexate, GnRH agonists to suppress menstruation. Subjects who completed treatment with these medications > 1 year ago are eligible to participate
- Current GCs (oral GC equivalent to 5mg prednisone or more). Subjects who completed treatment with these medications for ≤ 3 months, > 1 year ago are eligible to participate.
- Current anticoagulant use; past use of warfarin (Coumadin) or low molecular weight heparin is not an exclusion, although known thrombotic disease is an exclusion
- Depo Provera (depot medroxyprogesterone acetate) unless taken after age 20, more than 5 years ago
- Drugs for osteoporosis (raloxifene, bisphosphonates, denosumab, calcitonin, TPTD/abaloparatide): Subjects who discontinue these medications will be eligible:
- 3 months after stopping raloxifene or calcitonin
- 12 months after stopping abaloparatide, teriparatide, alendronate, risedronate, ibandronate, or pamidronate
- 24 months after the last dose of zoledronate
- 18 months after the last dose of denosumab. Subjects who have received ≤ 6 months of teriparatide or abaloparatide will be eligible 2 months after the last dose.
- Subjects who have received ≤ 12 months of teriparatide or abaloparatide will be eligible 6 months after the last dose.
- Women with a history of dental extraction or other invasive dental work within 3 months, or who require invasive dental work within the next two years, will be excluded
- Hypersensitivity to romosozumab or denosumab
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Romosozumab for Premenopausal Idiopathic Osteoporosis
The overarching goal of the research program is to define optimal treatment for premenopausal women with clinically significant fracture syndromes that require medical therapy. The investigators hypothesize that romosozumab will be associated with improvements in bone mass and microarchitecture in premenopausal women, and also that the responses and response rates will exceed those observed in premenopausal women treated with teriparatide. The investigators will test this hypothesis in this phase 2 study of 30 premenopausal women with idiopathic osteoporosis (IOP) who will receive 12M of romosozumab 210 mg monthly followed by 12M of denosumab 60 mg SC q6M. Aim 1 will define the within-group effects of this regimen. Aim 2 will compare results from participants treated with romosozumab-denosumab to the investigator's well-characterized historical controls treated with teriparatide followed by denosumab.
Read the detailed description
Romosozumab is an anti-sclerostin antibody that provides powerful skeletal benefits through concomitant osteoanabolic and antiresorptive effects on bone. In postmenopausal women, romosozumab is associated with larger increases in spine and hip BMD in comparison to teriparatide. Romosozumab has an extremely low reported nonresponse rate and transition to denosumab after romosozumab leads to further BMD increases and sustained anti-fracture efficacy.
Therefore, the investigators hypothesize that romosozumab will be associated with improvements in bone mass in premenopausal women, and also that the responses and response rates will exceed those observed in premenopausal women treated with teriparatide. The investigators will test this hypothesis in this phase 2 study of 30 premenopausal women with IOP who will receive 12M of romosozumab 210 mg monthly followed by 12M of denosumab 60 mg SC q6M ("romosozumab-denosumab").
Aim 1 will define the within-group effect of romosozumab-denosumab. The primary outcome variable will be the within-group change in areal BMD by DXA at the lumbar spine at 12M. Secondary outcome variables include change in aBMD by DXA at the total hip, femoral neck and 1/3 radius at 12M and change in aBMD at all sites at 24 months.
Aim 2 will compare results from participants treated with romosozumab-denosumab to the well-characterized historical controls treated with 24 months of teriparatide alone, and a subset of those treated with 24 months of teriparatide followed by 12 months of denosumab. The investigators hypothesize that romosozumab over 12M and romosozumab-denosumab over 24M will be associated with larger BMD gains compared to 12M and 24M of teriparatide. The investigators also hypothesize that 24M of romosozumab-denosumab will be associated with comparable BMD gains vs. historical controls treated with 36M of teriparatide-denosumab.
- Conditions
- Premenopausal Idiopathic Osteoporosis
- Being tested
- Romosozumab Prefilled Syringe [Evenity], Denosumab 60 MG/ML Prefilled Syringe [Prolia]
- Keywords
- denosumab, romosozumab, premenopausal osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Romosozumab Prefilled Syringe [Evenity]Drug
Also called Evenity
2 syringes of 105 MG/1.17 mL subcutaneous solution injected one after the other, once a month from study baseline through 11 month visit
Denosumab 60 MG/ML Prefilled Syringe [Prolia]Drug
Also called Prolia
1 subcutaneous injection of 60 mg/mL every six months from study 12 month visit through the 24 month visit. Injections occur at the 12 and 18 month visits.
| Study group | Role | What they receive |
|---|---|---|
| Romosozumab followed by denosumab | Experimental | Romosozumab 210 mg subcutaneous injection, once a month for 12 months followed by denosumab 60 mg subcutaneous injection, once every six months for 12 months. Receives: Drug: Romosozumab Prefilled Syringe [Evenity]; Drug: Denosumab 60 MG/ML Prefilled Syringe [Prolia] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in lumbar spine BMD by DXA
Within-group percent change in lumbar spine BMD by DXA at 12M
Measured: Baseline-12 months
Secondary outcomes (4)
Percent change in lumbar spine BMD by DXA
Within-group percent change in lumbar spine BMD every 6 months
Measured: Baseline, 6 month, 12 month, 18 month, 24 month
Percent change in total hip BMD by DXA
Within-group percent change in total hip BMD every 6 months
Measured: Baseline, 6 month, 12 month, 18 month, 24 month
Percent change in femoral neck BMD by DXA
Within-group percent change in femoral neck BMD every 6 months
Measured: Baseline, 6 month, 12 month, 18 month, 24 month
Percent change in distal radius BMD by DXA
Within-group percent change in distal radius BMD every 6 months
Measured: Baseline, 6 month, 12 month, 18 month, 24 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2021
- Study start12 Mar 2021
- Primary completionMar 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premenopausal Idiopathic OsteoporosisStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 12 months of romosozumab followed by 12 months of denosumab
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Adi Cohen, Columbia University
- Investigators
- Adi Cohen, MD, Principal investigator, Columbia UniversityElizabeth Shane, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04800367
- Sponsor's protocol ID
- AAAT1202
- Status last verified
- Feb 2026
- First submitted
- 12 Mar 2021
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Romosozumab for Premenopausal Idiopathic Osteoporosis
- ClinicalTrials.gov ID
- NCT04800367
- Acronym / sponsor ID
- AAAT1202
- Conditions
- Premenopausal Idiopathic Osteoporosis
- Keywords
- denosumab, romosozumab, premenopausal osteoporosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 12 Mar 2021 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 16 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overarching goal of the research program is to define optimal treatment for premenopausal women with clinically significant fracture syndromes that require medical therapy. The investigators hypothesize that romosozumab will be associated with improvements in bone mass and microarchitecture in premenopausal women, and also that the responses and response rates will exceed those observed in premenopausal women treated with teriparatide. The investigators will test this hypothesis in this phase 2 study of 30 premenopausal women with idiopathic osteoporosis (IOP) who will receive 12M of romosozumab 210 mg monthly followed by 12M of denosumab 60 mg SC q6M. Aim 1 will define the within-group effects of this regimen. Aim 2 will compare results from participants treated with romosozumab-denosumab to the investigator's well-characterized historical controls treated with teriparatide followed by denosumab.
Detailed description
Romosozumab is an anti-sclerostin antibody that provides powerful skeletal benefits through concomitant osteoanabolic and antiresorptive effects on bone. In postmenopausal women, romosozumab is associated with larger increases in spine and hip BMD in comparison to teriparatide. Romosozumab has an extremely low reported nonresponse rate and transition to denosumab after romosozumab leads to further BMD increases and sustained anti-fracture efficacy.
Therefore, the investigators hypothesize that romosozumab will be associated with improvements in bone mass in premenopausal women, and also that the responses and response rates will exceed those observed in premenopausal women treated with teriparatide. The investigators will test this hypothesis in this phase 2 study of 30 premenopausal women with IOP who will receive 12M of romosozumab 210 mg monthly followed by 12M of denosumab 60 mg SC q6M ("romosozumab-denosumab").
Aim 1 will define the within-group effect of romosozumab-denosumab. The primary outcome variable will be the within-group change in areal BMD by DXA at the lumbar spine at 12M. Secondary outcome variables include change in aBMD by DXA at the total hip, femoral neck and 1/3 radius at 12M and change in aBMD at all sites at 24 months.
Aim 2 will compare results from participants treated with romosozumab-denosumab to the well-characterized historical controls treated with 24 months of teriparatide alone, and a subset of those treated with 24 months of teriparatide followed by 12 months of denosumab. The investigators hypothesize that romosozumab over 12M and romosozumab-denosumab over 24M will be associated with larger BMD gains compared to 12M and 24M of teriparatide. The investigators also hypothesize that 24M of romosozumab-denosumab will be associated with comparable BMD gains vs. historical controls treated with 36M of teriparatide-denosumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 12 months of romosozumab followed by 12 months of denosumab
| Arm | Type | Receives |
|---|---|---|
| Romosozumab followed by denosumab | Experimental | Drug: Romosozumab Prefilled Syringe [Evenity], Drug: Denosumab 60 MG/ML Prefilled Syringe [Prolia]Romosozumab 210 mg subcutaneous injection, once a month for 12 months followed by denosumab 60 mg subcutaneous injection, once every six months for 12 months. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Premenopausal women, aged 18-48, with regular menses and no historical or biochemical secondary cause of osteoporosis; the lower age limit is to ensure epiphyses are fused, the upper to make it less likely that women will enter menopause during the study. All subjects under age 25 will be screened (bone age radiograph) prior to enrollment to rule out open epiphyses.
- Highly effective contraception includes methods considered by the CDC to be >99% effective (e.g. vasectomized partner, tubal ligation, hysterectomy, IUD) as well as a combination of barrier method (condoms) with hormonal contraception considered to be > 90% effective (oral contraceptive pill, patch or ring). Systemic progestin only methods (oral or implanted) are not included due to their effect on systemic estrogen levels and thus potential effects on bone health in this premenopausal population.
Key exclusion criteria (30 listed)
- Any cardiovascular disease: history of myocardial infarction (MI) or stroke. Normal electrocardiogram (ECG) or ECG with no clinically significant abnormality is required at study entry.
- Conditions requiring chronic anticoagulation (coumadin, heparins)
- Early follicular phase serum FSH>20 mIU/ml (to exclude perimenopausal women)
- Disorders of mineral metabolism: primary/secondary hyperparathyroidism, osteomalacia (including that associated with a diagnosis of hypophosphatasia), vitamin D deficiency
- Current pregnancy or lactation
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 |
|---|---|---|
| Romosozumab Prefilled Syringe [Evenity]Also: Evenity2 syringes of 105 MG/1.17 mL subcutaneous solution injected one after the other, once a month from study baseline through 11 month visit | Drug | Romosozumab followed by denosumab |
| Denosumab 60 MG/ML Prefilled Syringe [Prolia]Also: Prolia1 subcutaneous injection of 60 mg/mL every six months from study 12 month visit through the 24 month visit. Injections occur at the 12 and 18 month visits. | Drug | Romosozumab followed by denosumab |
Primary outcome
Percent change in lumbar spine BMD by DXA
Time frame: Baseline-12 months
Within-group percent change in lumbar spine BMD by DXA at 12M
4 secondary outcomes
Percent change in lumbar spine BMD by DXA
Time frame: Baseline, 6 month, 12 month, 18 month, 24 month
Percent change in total hip BMD by DXA
Time frame: Baseline, 6 month, 12 month, 18 month, 24 month
Percent change in femoral neck BMD by DXA
Time frame: Baseline, 6 month, 12 month, 18 month, 24 month
Percent change in distal radius BMD by DXA
Time frame: Baseline, 6 month, 12 month, 18 month, 24 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
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.
Adi Cohen, MD principal investigator
Columbia University
Elizabeth Shane, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Romosozumab Prefilled Syringe [Evenity] and Denosumab 60 MG/ML Prefilled Syringe [Prolia] in people with Premenopausal Idiopathic Osteoporosis, run by Columbia University at 1 site in United States.
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 4 inclusion and 30 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: under way, not looking for participants, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Percent change in lumbar spine BMD by DXA (time frame: Baseline-12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Feb 2026.