Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI

NCT04232657 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: B3415-RBAU-19-661600530
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

Treatment for sublesional bone loss (osteoporosis) in persons with chronic, motor-complete spinal cord injury (SCI) has been limited and unsuccessful to date. Romosozumab, a sclerostin antagonist, has potential to increase bone formation (anabolic) and decrease bone resorption (anti-catabolic) in persons with chronic SCI. Conventional anti-resorptive therapy alone would not be anticipated to reverse sublesional bone loss in a timely manner because the skeleton below the level of lesion in chronic SCI is assumed to be in a low turnover state. However, because there is a high likelihood that the bone accrued while on romosozumab will be lost once discontinued, denosumab, an anti-resorptive agent, will be administered after treatment with romosozumab, to maintain or, possibly, to continue to increase, bone mineral density (BMD). 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 \<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.

Conditions

Spinal Cord Injury (=3 Years); Sublesional Bone Loss Secondary to SCI

Keywords

Spinal Cord Injury; Veterans Affairs RR&D; Sublesional Bone Loss

Outcome Measures

Primary Outcomes (2)

• Change in vBMD at the Distal Femur, measured by pQCT after 12 months of romosozumab treatment

  Percent change of volumetric BMD (vBMD) (mg/cm\^3)at the distal femur, measured by peripheral quantitative computed tomography (pQCT) (slice thickness 2.4mm, default voxel size of 0.5mm), with 12 months of romosozumab therapy. vBMD measurements will be taken at baseline, month 6 and month 12.

  Baseline (0), Month 6, Month 12

• Change in vBMD at the distal femur after an additional 12 months of denosumab treatment

  Percent change of Integral vBMD (mg/cm\^3)at the distal femur, measured by pQCT (slice thickness 2.4mm, default voxel size of 0.5mm), after additional 12 months of denosumab therapy. vBMD measurements will be taken by pQCT at months 18 and 24.

  Month 18, Month 24

Other Outcomes (27)

• Additional variables by pQCT - vBMD Proximal Tibia

  Baseline (0), Month 6, Month 12, Month 18, Month 24

• Additional variables by pQCT - tBMD Distal Femur

  Baseline (0), Month 6, Month 12, Month 18, Month 24

• Additional variables by pQCT - tBMD Proximal Tibia

  Baseline (0), Month 6, Month 12, Month 18, Month 24

Study Arms (3)

Romosozumab Treatment (baseline to month 11)

EXPERIMENTAL

Of the thirty-nine (39) individuals with chronic spinal cord injury (SCI) enrolled in this study, twenty-six (26) participants will be randomly selected to received romosozumab (210mg SQ) once a month for 12 months.

Drug: Romosozumab

Placebo (baseline to month 12)

PLACEBO COMPARATOR

Of the thirty-nine (39) individuals with chronic SCI enrolled in this study, thirteen (13) participants will be randomly selected to received placebo injections (NS SQ) once a month for 12 months. They will follow study procedures identical to those performed by individuals in the treatment (romosozumab) group.

Drug: Placebo

Denosumab (month 12 to month 24)

ACTIVE COMPARATOR

Both groups (treatment and placebo) will receive denosumab (60mg SQ) at months 12 and 18 for maintenance of or to further increase bone mineral density (BMD) at regions of interest (ROI).

Drug: Denosumab

Interventions

Romosozumab DRUG

39 subjects with chronic SCI will be studied with a 2:1 ratio of randomization of drug to placebo. Romosozumab (210mg SQ) will be administered once a month for 12 months. Participants will arrive at the JJPVAMC or KIR once a month to receive injections of romosozumab or placebo. A designated unblinded healthcare professional will be responsible for administering these injections.

Also known as: Evenity

Romosozumab Treatment (baseline to month 11)

Denosumab DRUG

Because there is a high likelihood that the bone accrued while on romosozumab will be lost once discontinued, denosumab, an anti-resorptive agent, will be administered after treatment with romosozumab, to maintain or, possibly, to continue to increase, bone mineral density. Denosumab will be administered to both groups (treatment and placebo) for an additional 12 months. Participants will be asked to arrive at the JJPVAMC once every 6 months to receive injections of denosumab by a healthcare professional.

Also known as: Prolia

Denosumab (month 12 to month 24)

Placebo DRUG

Thirteen (13) of the thirty-nine (39) subjects enrolled in this study will be randomly selected to receive placebo (NS SQ) injections for 12 months (baseline - month 11). The placebo injections will be administered by an unblinded healthcare professional (registered nurse / physician). Participants will be blinded to their group assignment (romosozumab treatment or placebo).

Also known as: Normal Saline (NS) injection

Placebo (baseline to month 12)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Motor-complete or incomplete SCI \[all levels of lesion\] classified using International Standards for Neurological Classification for Spinal Cord Injury (ISNCSCI) impairment scale\] as ISNCSCI score A-C
• Duration of injury \>3 years
• Males (18-65 years old) and females (premenopausal, between the ages of 18 and 55 years old).
• aBMD at the distal femur \<1.0 g/cm2 (determined at screening)

You may not qualify if:

• Long-bone fracture of the leg within the past year
• History of prior bone disease (Paget's hyperparathyroidism, etc.)
• Active and/or history of coronary heart disease or stroke within the past year
• Postmenopausal women
• Men with known hypogonadism prior to SCI
• Anabolic therapy longer than six months duration after SCI
• Glucocorticoid administration longer than three months duration within the last year, and/or 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
• Endocrinopathies (hyperthyroidism, Cushing's disease or syndrome, etc.)
• Severe underlying chronic disease (e.g., COPD, end-stage heart disease, chronic renal failure)
• Heterotopic ossification (HO) of the knee region (the distal femoral epiphysis is the primary endpoint); HO to any other boney region will not prevent study participation as long as contraindicated medications have not been prescribed)
• Chronic alcohol abuse
• Hypocalcemia
• Pregnancy
• Prescribed a bisphosphonate for HO, or prescribed any other agent to treat osteoporosis other than calcium and vitamin D
• Electrical stimulation of the lower extremities

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Kessler Institute for Rehabilitation: collaborator

Study Sites (2)

Kessler Institute for Rehabilitation

West Orange, New Jersey, 07052, United States

Location

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, 10468-3904, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

romosozumab; Denosumab; Saline Solution

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Christopher Cardozo, MD

  James J. Peters Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and study investigators / team members will be blinded to the treatment group assignment. The designated study drug administrator will be the only individual unblinded. This individual will administer the drug/placebo saline injections behind a sheet.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, parallel group clinical trial

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: January 18, 2020
• Study Start: March 1, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)