Romosozumab in Women With Chronic SCI

Sponsor

Northwestern University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04708886

Collaborator

Amgen (Industry)

Enrollment

Location

Arm

47.1

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis Bone Loss Osteopenia, Osteoporosis Spinal Cord Injuries Chronic Spinal Paralysis	Drug: Romosozumab Drug: Alendronate	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Females with Chronic SCI 12-month treatment with monthly subcutaneous romosozumab injections (210 mg), followed by 12-month treatment with weekly oral alendronate tablets (70 mg)	Drug: Romosozumab Year 1 study drug Other Names: Evenity Drug: Alendronate Year 2 study drug Other Names: Fosamax

Arm

Intervention/Treatment

Experimental: Females with Chronic SCI

12-month treatment with monthly subcutaneous romosozumab injections (210 mg), followed by 12-month treatment with weekly oral alendronate tablets (70 mg)

Drug: Romosozumab

Year 1 study drug

Other Names:

Evenity

Drug: Alendronate

Year 2 study drug

Other Names:

Fosamax

Outcome Measures

Primary Outcome Measures

Change in knee integral vBMC [Baseline - 12 months]
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

Secondary Outcome Measures

Change in hip BMD [Baseline - 12 months]
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
Change in hip vBMC [Baseline - 12 months]
Change from baseline to the Month 12 visit in vBMC at the hip as obtained via CT imaging of the index hip

Other Outcome Measures

Change in BMC and BMD at regions of interest around the knee [Baseline - 12 months]
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
Change in serum bone markers [Baseline - 12 months]
Change from baseline to the Month 12 visit in serum biomarkers of bone turnover

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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