Romosozumab in Women With Chronic SCI

Osteoporosis Clinical Trial

Official title:

Effects of Romosozumab on Bone Health in Women With Spinal Cord Injury and Osteoporosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04708886
• Other study ID #: STU00212405
• Secondary ID: 20197268
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 1, 2021
• Est. completion date: February 1, 2025

Study information

• Verified date: January 2024
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This two-year open-label pilot clinical trial will evaluate the efficacy and safety of romosozumab to treat bone loss in females with chronic spinal cord injury (SCI) and osteoporosis (OP). Participants will receive monthly injections of romosozumab during the first 12 months of the study. During the second year, participants will take oral alendronate tablets on a weekly basis.

Description:

This is a single-site, singe-arm, open-label pilot study to evaluate safety and efficacy of a sequential drug treatment (12 months of romosozumab injections followed by 12 months with alendronate tablets) to treat bone loss in women with chronic SCI and OP.

During the first year, participants will receive monthly subcutaneous injections of romosozumab 210 mg. This drug works by increasing bone formation and is FDA-approved for treating OP in post-menopausal women at high risk of fracture or those who did not benefit from using other available OP treatments. During the second year, participants will take weekly oral alendronate 70 mg. Alendronate is FDA-approved for the treatment of osteopenia and the treatment of OP in post-menopausal women and men as well as for the prevention and treatment of glucocorticoid-induced OP. In this study, it will be used to help maintain any increases in bone mass gained from the year of treatment with romosozumab.

Twelve participants will receive the study drug treatment, take daily supplements (calcium and vitamin D), and return to the research site for study visits over the course of two years. Computerized tomography (CT) imaging, dual-energy X-ray absorptiometry (DXA) imaging, and serum bone markers will be collected at baseline, 3 months, 6 months, 12 months, and 24 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: February 1, 2025
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years

• Female sex

• SCI 6 or more months prior to enrollment

• Non-ambulatory status (Walking Index for Spinal Cord Injury II score of 3 or less)

• Osteoporosis by DXA defined as a t-score of -2.5 at any skeletal site (lumbar spine, total hip, or femoral neck) or a t-score of -2.0 plus a history of a fragility fracture

• Good general health, as determined by the study investigator

• Able to understand and agree to informed consent in English

• Able and willing to complete all the study visits

• Females of childbearing potential must be willing and able to use an effective method of contraception or practice abstinence throughout the course of the study and up to 90 days after the last use of study drug.

• Vitamin D 25-hydroxy levels = 20 ng/ml (subjects may be repleted and retested prior to baseline)

• Normal serum calcium levels (based on current local laboratory normal range)

• No known endocrinopathies (diabetes type 1 or 2, treated thyroid conditions can be included)

• Normal serum thyroid stimulating hormone and/or T4 levels (based on current local laboratory normal ranges)

• Able to take oral medication sitting upright for at least 30 minutes

Exclusion criteria:

• Have Paget's disease of the bone

• Have abnormal laboratory values that in the judgement of the investigator would put the participant at increased risk of treatment

• Any active gastrointestinal condition that results in malabsorption

• Abnormalities of the esophagus which delay emptying such as stricture or achalasia

• Known hypersensitivity to romosozumab or alendronate

• Increased risk of aspiration

• Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease, or planned invasive dental procedure over the next two years

• Heterotopic ossification of the knee region that interferes with CT analysis

• History of bone metastasis and skeletal malignancies

• History of alcoholism or drug abuse within the 2 years prior to study screening, which in the opinion of the investigator may affect subject's health and/or study commitment

• Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study

• Currently being prescribed anticonvulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator

• Currently being prescribed glucocorticoids, other than inhaled glucocorticoids

• Current or use during past 5 years of any bone-active agents, including any FDA approved treatment (e.g., teriparatide, abaloparatide, denosumab, any bisphosphonate (oral or IV), raloxifene, bazedoxifene, hormone therapy (estrogen and estrogen/progestin) and calcitonin) as well as any strontium-containing compounds.

• Pregnant, planning to become pregnant, or lactating

• Any history of stroke or cardiovascular disease other than controlled hypertension

• Renal insufficiency (calculated creatinine clearance less than 35 ml/min)

• Any other neurological impairment that may impair ambulation or muscle function

Related Conditions & MeSH terms

• Bone Diseases, Metabolic
• Bone Loss
• Chronic Spinal Paralysis
• Osteopenia, Osteoporosis
• Osteoporosis
• Paralysis
• Spinal Cord Injuries

Intervention

Drug:
• Romosozumab
Year 1 study drug
• Alendronate
Year 2 study drug

Locations

Country	Name	City	State
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Amgen

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

Keaveny TM, Crittenden DB, Bolognese MA, Genant HK, Engelke K, Oliveri B, Brown JP, Langdahl BL, Yan C, Grauer A, Libanati C. Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass. J Bone Miner Res. 2017 Sep;32(9):1956-1962. doi: 10.1002/jbmr.3176. Epub 2017 Jun 26. — View Citation

Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in BMC and BMD at regions of interest around the knee	Change from baseline to the Month 12 visit in BMC and BMD in the femur and tibia as collected via CT imaging of the index knee	Baseline - 12 months
Other	Change in serum bone markers	Change from baseline to the Month 12 visit in serum biomarkers of bone turnover	Baseline - 12 months
Primary	Change in knee integral vBMC	Change from baseline to the Month 12 visit in integral volumetric bone mineral content (vBMC) at the distal femur as obtained via CT imaging of the index knee	Baseline - 12 months
Secondary	Change in hip BMD	Change from baseline to the Month 12 visit in bone mineral density (BMD) at the total hip and femoral neck as obtained via DXA imaging of the index hip	Baseline - 12 months
Secondary	Change in hip vBMC	Change from baseline to the Month 12 visit in vBMC at the hip as obtained via CT imaging of the index hip	Baseline - 12 months