Clinical trial NCT05067335: A Study to Test the Efficacy, Safety and Tolerability of Romosozumab Treatment in Postmenopausal Chinese Women With Osteoporosis
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Romosozumab Treatment in Postmenopausal Chinese Women With Osteoporosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Keywords: Osteoporosis
Phase 3
Chinese Patients
Romosozumab
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2021-10-05
Enrollment: 327
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the effect of treatment with romosozumab for 6 months compared with placebo on the percent changes in bone mineral density (BMD) at the lumbar spine, at the total hip and femoral neck in postmenopausal Chinese women with osteoporosis.


Eligibility criteria: Inclusion Criteria:

* Subject is considered reliable and capable of adhering to the protocol, visit schedule, and medication intake according to the judgment of the investigator
* Subject is an ambulatory postmenopausal Chinese women, 55 to 90 years of age (inclusive) at the time of Screening. Postmenopause is defined as no spontaneous vaginal bleeding or spotting for 12 or more consecutive months prior to Screening
* Subject has a bone mineral density (BMD) T-score ≤-2.50 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of Screening based on DXA scans, and using data for Caucasian women from the National Health and Nutritional Examination Survey (NHANES, 1998)
* Subject must have at least 1 of following independent risk factors for fracture:

  * History of fragility fracture (except hip fracture, a severe vertebral fracture or more than 2 moderate vertebral fractures)
  * Parental history of hip fracture
  * Low body weight (body mass index ≤19kg/m2)
  * Elderly (age ≥ 65 years)
  * Current smoker
* Subject has at least 2 vertebrae in the L1 to L4 region and at least 1 hip that are evaluable by dual-energy x-ray absorptiometry (DXA), as assessed by the central imaging vendor

Exclusion Criteria:

* Subject has a BMD T-score of ≤-3.50 at the total hip or femoral neck, as assessed by the central imaging vendor at the time of Screening based on DXA scans, and using data for Caucasian women from NHANES 1998
* Subject has a known history of hip fracture
* Subject has any severe (SQ3) or more than 2 moderate (SQ2) vertebral fractures, as assessed by the central imaging vendor based on the lateral spine x-ray at Screening
* Subject has a history of myocardial infarction (MI)
* Subject has a history of stroke
* Subject has a vitamin D insufficiency, defined as 25 (OH) vitamin D levels \<20 ng/mL, as assessed by the central laboratory at Screening. Vitamin D repletion will be permitted and the subject may be retested once within the Screening Period
* Subject has used oral bisphosphonates:

  * Any doses received within 3 months prior to randomization
  * More than 1 month of cumulative use between 3 and 12 months prior to randomization
  * More than 3 years of cumulative use, unless the last dose was received ≥5 years prior to randomization
* Subject has used intravenous (iv) bisphosphonates:

  * zoledronic acid

    * Any doses received within 3 years prior to randomization
    * More than 1 dose received within 5 years prior to randomization
  * iv ibandronate, iv pamidronate, or iv alendronate (ALN)

    * Any doses received within 12 months prior to randomization
    * More than 3 years of cumulative use, unless the last dose was received ≥5 years prior to randomization
* Subject has used denosumab or any cathepsin K inhibitor:

  ● Any doses received within 18 months prior to randomization
* Subject has used tibolone, cinacalcet, or calcitonin:

  * Any doses received within 3 months prior to randomization
* Subject has used teriparatide (TPTD) or any parathyroid hormone (PTH) derivative:

  * Any doses received within 3 months prior to randomization
  * More than 1 month of cumulative use between 3 and 12 months prior to randomization
* Subject has used systemic oral or transdermal estrogen or selective estrogen receptor modulators (SERMs):

  ● More than 1 month of cumulative use within 6 months prior to randomization
* Subject has used strontium ranelate or fluoride:

  ● More than 1 month of cumulative use within 5 years prior to randomization
* Subject has used hormonal ablation therapy:

  ● More than 1 month of cumulative use within 6 months prior to randomization
* Subject has used systemic glucocorticosteroids:

  ● ≥5mg prednisone equivalent per day for more than 14 days within 3 months prior to randomization
* Subject has a history of osteonecrosis of the jaw (ONJ) or atypical femoral fracture (AFF)
* Subject has evidence of any of the following:

  1. Current, uncontrolled hyper- or hypothyroidism. Uncontrolled hyperthyroidism is defined as thyroid-stimulating hormone (TSH) and thyroxine (T4) outside of the normal range. Uncontrolled hypothyroidism is defined as TSH \>10
  2. Current, uncontrolled hyperparathyroidism or history of hypoparathyroidism. Uncontrolled hyperparathyroidism is defined as PTH outside the normal range in subjects with concurrent hypercalcemia or PTH values \>20 % above upper limit of normal (ULN) in normocalcemic subjects
  3. Current hypercalcemia or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory at the time of Screening. Albumin-adjusted serum calcium levels may be retested once in case of an elevated albumin-adjusted serum calcium level within 1.1xULN of the laboratory's reference ranges
  4. Subject has ≥3xULN of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or \>ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are \>ULN and \<1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin \<35 %)

Primary outcomes:
measure: Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine to the End of Double-Blind Period
timeFrame: From Baseline (Day 1) to the end of the Double-blind Period (Month 6)
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period
timeFrame: From Baseline to the end of the Double-blind Period (Month 6)
measure: Percentage of Participants With Treatment-emergent Adverse Events for Romosozumab During Overall Period
timeFrame: From Month 7 up to Month 12 (Placebo/Romo) and From Day 1 up to Month 12 (Romo/Romo) + 3-month SFU (up to Month 15)
Secondary outcomes:
measure: Percent Change From Baseline in Bone Mineral Density at the Total Hip to the End of Double-Blind Period
timeFrame: From Baseline to the end of the Double-blind Period (Month 6)
measure: Percent Change From Baseline in Bone Mineral Density at the Femoral Neck to the End of the Double-Blind Period
timeFrame: From Baseline to the end of the Double-blind Period (Month 6)
measure: Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12
timeFrame: Baseline, Month 12
measure: Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Beijing
country: China
facility: Op0002 20040
city: Beijing
country: China
facility: Op0002 20115
city: Beijing
country: China
facility: Op0002 20125
city: Beijing
country: China
facility: Op0002 20127
city: Beijing
country: China
facility: Op0002 20128
city: Beijing
country: China
facility: Op0002 20130
city: Beijing
country: China
facility: Op0002 20131
city: Beijing
country: China
facility: Op0002 20157
city: Chengdu
country: China
facility: Op0002 20021
city: Chengdu
country: China
facility: Op0002 20133
city: Chengdu
country: China
facility: Op0002 20137
city: Foshan
country: China
facility: Op0002 20205
city: Guangzhou
country: China
facility: Op0002 20117
city: Guangzhou
country: China
facility: Op0002 20124
city: Nanchang
country: China
facility: Op0002 20209
city: Nanjing
country: China
facility: Op0002 20135
city: Pingxiang
country: China
facility: Op0002 20202
city: Rui'an
country: China
facility: Op0002 20199
city: Shanghai
country: China
facility: Op0002 20116
city: Shanghai
country: China
facility: Op0002 20118
city: Shanghai
country: China
facility: Op0002 20121
city: Shanghai
country: China
facility: Op0002 20123
city: Shanghai
country: China
facility: Op0002 20129
city: Suzhou
country: China
facility: Op0002 20119
city: Suzhou
country: China
facility: Op0002 20204
city: Tianjin
country: China
facility: Op0002 20122
city: Tianjin
country: China
facility: Op0002 20136
city: Wuhan
country: China
facility: Op0002 20120
city: Yueyang
country: China
facility: Op0002 20134
city: Zhengzhou
country: China
facility: Op0002 20132
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: