Treatment With Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI

Study Overview
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Brief Summary
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The objective of the proposed work is to determine whether administration for 12 months of romosozumab (evenity) followed by 12 months of denosumab (prolia) will maintain bone mass at the knee in subjects with chronic SCI.

Detailed Description
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The purpose of this study is to address the gap in the treatment of osteoporosis in individuals with chronic SCI by partially restoring BMD with romosozumab treatment for 12 months and then to maintain, or further increase, BMD with denosumab treatment for 12 months. A two group, randomized, double-blind, placebo-controlled clinical trial will be conducted in 39 participants who have chronic (> 3 years), motor-complete or incomplete SCI and areal BMD (aBMD) values at the distal femur of at the distal femur ≥0.6 g/cm2 but ≤1.0 g/cm2 measured by dual photon X-ray absorptiometry (DXA). The intervention group will receive 12 months of romosozumab followed by 12 months of denosumab, and the control group will receive 12 months of placebo followed by 12 months denosumab

Official Title
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Treatment With Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI

Conditions
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Osteoporosis, Spinal Cord Injuries

Intervention / Treatment
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* Drug: Romoszumab
* Drug: Denosumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Motor complete or incomplete SCI (every level of injury); International Standards for Neurological Classification of Spinal Cord Injury (ISNSCI) grade A-C (wheelchair dependent greater than 75% of the time) 2) Duration of SCI greater than 3 years; 3) Males between the ages of 18 and 65 years old or females (premenopausal) between the ages of 18 and 55 years old (the upper age limit is to reduce the influence of age on the ability of the skeleton to respond to pharmacologic stimulation); 4) aBMD at the distal femur greater less than or equal to 1.0 g/cm2; 5) Agreement to use a highly effective contraceptive method for women of reproductive potential. Exclusion Criteria: 1) Active and/or history of coronary heart disease or stroke; 2) Bone cancer; 3) Long-bone fracture of the leg within the past year; 4) Postmenopausal women; 5) Men with known low functioning testes before SCI; 6) Medication designed to increase bone density longer than six months after duration of SCI; 7) As determined by study staff review of my medication, glucocorticoid (anti-inflammatory medications) administration longer than three months duration within the last year; 8) Endocrinopathies such as the following: hyperthyroidism (overproduction of a hormone known as thyroxine by the thyroid gland in the neck), Cushing's disease or syndrome (excess production of the steroid hormone cortisol), etc.; 9) Severe underlying chronic disease [for example chronic obstructive pulmonary (lung) disease (COPD, end-stage heart disease, chronic renal (kidney) failure]; 10) Heterotopic ossification (HO- an abnormal growth of bone that can occur after SCI) at the distal femur (the distal femur is the primary outcome variable; HO to any other boney region will not prevent study participation); 11) As determined by study staff review of my medication, prescribed a bisphosphonate for heterotopic ossification (HO), or prescribed any other agent to treat osteoporosis other than calcium and vitamin D; 12) History of chronic alcohol abuse; 13) Diagnosis of hypercalcemia (excess calcium levels in the blood); 14) Diagnosis of hypocalcemia (low calcium levels in the blood). If corrected, subject may still be eligible for study participation); 15) Pregnancy, or plans to become pregnant within 6 months after the end of study treatment; 16) Lactation; 17) Current diagnosis of cancer or history of cancer within the last 5 years; 18) As determined by study staff review of my medication, prescribed moderate or high dose corticosteroids (>40 mg/d prednisone or an equivalent dose of other corticosteroid medication) for longer than one week, not including drug administered to preserve neurological function at the time of acute SCI; 19) As determined by study staff review of my medical records, life expectancy less than 5 years; 20) History of hypersensitivity reaction (including allergic reaction, facial swelling and hives) to any Prolia (denosumab) or Evenity (romosozumab) component; 21) Currently experiencing a weakened immune system or infection; 22) Recent fracture or extensive bone trauma; 23) Osteonecrosis of the jaw (ONJ- deterioration of the jaw bone) or risk for ONJ, such as invasive dental procedures (including tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease; 24) Planned invasive dental procedure over the next two years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab group<br>Romosozumab (evenity) administered monthly from baseline to month 11 followed by denosumab (prolia) at month 12 and 18 | Drug: Romoszumab<br>* Monthly SQ injections<br>* Other names: Evenity;Drug: Denosumab<br>* 2 injections 6 months apart SQ<br>* Other names: Prolia;|
| Placebo Comparator: Control group<br>Placebo administered monthly from baseline to month 11 followed by denosumab (prolia) at month 12 and 18 | Drug: Denosumab<br>* 2 injections 6 months apart SQ<br>* Other names: Prolia;Drug: Placebo<br>* Monthly Placebo Injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density (BMD) | BMD of the distal femur metaphysis | Baseline to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Spinal Cord Injuries, Denosumab, Romosozumab, Dual Energy X-ray Absorptiometry