Romosozumab/Denosumab Study for Premenopausal IOP

  • STATUS
    Recruiting
  • End date
    Mar 4, 2026
  • participants needed
    30
  • sponsor
    Columbia University
Updated on 4 April 2021

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, 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.

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.

Details
Condition Premenopausal Idiopathic Osteoporosis
Treatment Romosozumab Prefilled Syringe [Evenity], Denosumab 60 MG/ML Prefilled Syringe [Prolia]
Clinical Study IdentifierNCT04800367
SponsorColumbia University
Last Modified on4 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Premenopausal women, aged 18-45, 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

Exclusion Criteria

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
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
Prolonged amenorrhea (> 12 months) during reproductive years (except pregnancy or lactation)
Prior eating disorder (hypothalamic or exercise induced amenorrhea now resolved may be acceptable if symptoms occurred at age >20 years, for <1year, >5 years ago). The Eating Aptitude Test -Questionnaire is given to identify women with subclinical eating disorders
Malignancy, except cured basal or squamous cell skin carcinoma
Use of angiogenesis inhibitors
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 disorders including but not limited to celiac disease, pancreatic insufficiency, Crohn Disease or ulcerative colitis
History/current GCs, anticonvulsants, anticoagulants, methotrexate, GnRH agonists to suppress menstruation
Oral glucocorticoid dose equivalent >5 mg prednisone for >3 months
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). Subjects who discontinue these medications will be eligible 3 months after stopping raloxifene or calcitonin, 12 months after stopping alendronate, risedronate, ibandronate, or pamidronate and 18 months after stopping denosumab. Subjects with prior use of zoledronate may be eligible if received only one dose >4 years ago. Total bisphosphonate/denosumab exposure must be < 1 year. Subjects who have taken TPTD in the past will not be eligible unless used for <3 months, > 2 years ago
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note