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

• Sponsor: James J. Peters Veterans Affairs Medical Center (U.S. Fed)
• Overall Status: Recruiting
• CT.gov ID: NCT05180032
• Collaborator: Kessler Institute for Rehabilitation (Industry)
• Enrollment: 39
• Locations: 2
• Arms: 2
• Anticipated Duration (Months): 72
• Patients Per Site: 19.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis; Spinal Cord Injuries	Drug: Romoszumab; Drug: Denosumab; Drug: Placebo	Phase 4

Detailed Description

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 (3-15 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

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Treatment With Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI
• Actual Study Start Date: Mar 1, 2021
• Anticipated Primary Completion Date: Mar 1, 2025
• Anticipated Study Completion Date: Mar 1, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Bone mineral density (BMD) [Baseline to 24 months]

   BMD of the distal femur metaphysis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. Motor complete or incomplete SCI C4 and below {upper motor lesions; International Standards for Neurological Classification of Spinal Cord Injury (ISNSCI) grade A-C (wheelchair dependent greater than 75% of the time)
• 1. Duration of SCI between 3-15 years;
• 1. Males and females (premenopausal) between the ages of 18 and 50 years old (the upper age limit is to reduce the influence of age on the ability of the skeleton to respond to pharmacologic stimulation);
• 1. aBMD at the distal femur greater than or equal to 0.6 g/cm2 but less than or equal to 1.0 g/cm2;
• 1. 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;
• 1. Bone cancer;
• 1. Long-bone fracture of the leg within the past year;
• 1. History of prior bone disease [for example Paget's hyperparathyroidism (overproduction of a steroid hormone known as the parathyroid hormone), osteoporosis, etc.];
• 1. Postmenopausal women;
• 1. Men with known low functioning testes before SCI;
• 1. Medication designed to increase bone density longer than six months after duration of SCI;
• 1. As determined by study staff review of my medication, glucocorticoid (anti-inflammatory medications) administration longer than three months duration within the last year;
• 1. 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.;
• 1. Severe underlying chronic disease [for example chronic obstructive pulmonary (lung) disease (COPD, end-stage heart disease, chronic renal (kidney) failure];
• 1. 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);
• 1. 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;
• 1. History of chronic alcohol abuse;
• 1. Diagnosis of hypercalcemia (excess calcium levels in the blood);
• 1. Diagnosis of hypocalcemia (low calcium levels in the blood). If corrected, subject may still be eligible for study participation);
• 1. Pregnancy, or plans to become pregnant within 6 months after the end of study treatment;
• 1. Lactation;
• 1. Current diagnosis of cancer or history of cancer within the last 5 years;
• 1. 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;
• 1. As determined by study staff review of my medical records, life expectancy less than 5 years;
• 1. History of hypersensitivity reaction (including allergic reaction, facial swelling and hives) to any Prolia (denosumab) or Evenity (romosozumab) component;
• 1. Currently experiencing a weakened immune system or infection;
• 1. Recent fracture or extensive bone trauma;
• 1. 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;
• 1. Planned invasive dental procedure over the next two years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kessler Institute for Rehabilitation	West Orange	New Jersey	United States	07052
2	James J. Peters VA Medical Center	Bronx	New York	United States	10468

Sponsors and Collaborators

• James J. Peters Veterans Affairs Medical Center
• Kessler Institute for Rehabilitation

Investigators

• Principal Investigator: William A Bauman, MD, James J Peters VA Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: William A. Bauman, M.D., Director VA RR&D National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center
• ClinicalTrials.gov Identifier: NCT05180032
• Other Study ID Numbers: BAU-19-66
• First Posted: Jan 6, 2022
• Last Update Posted: Apr 11, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by William A. Bauman, M.D., Director VA RR&D National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center: Osteoporosis; Spinal Cord Injuries; Denosumab; Romosozumab; Dual Energy X-ray Absorptiometry
• Additional relevant MeSH terms: Osteoporosis; Spinal Cord Injuries; Denosumab

Study Results

No Results Posted as of Apr 11, 2022