Romosozumab for Osteoporosis in Chronic Spinal Cord Injury

(Chronic Romo Trial)

Recruiting at 1 trial location

Overseen By Christopher Cardozo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Bisphosphonates, Anabolic therapy, Corticosteroids

Disqualifiers: Coronary heart disease, Stroke, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking certain medications like bisphosphonates for heterotopic ossification or other osteoporosis treatments, you may not be eligible to participate.

What data supports the effectiveness of the drug Romosozumab for osteoporosis in chronic spinal cord injury?

Research shows that Romosozumab is effective in treating osteoporosis by reducing new fractures and significantly increasing bone density in the spine over 12 months, especially in patients not previously treated with other osteoporosis medications. ^{1 2 3 4 5}

Is romosozumab safe for humans?

Romosozumab has been studied in several clinical trials for osteoporosis, showing it is generally safe, but there may be potential cardiovascular risks (related to the heart and blood vessels) associated with its use. ^{2 3 4 6 7}

How does the drug Romosozumab differ from other treatments for osteoporosis in chronic spinal cord injury?

Romosozumab is unique because it is a monoclonal antibody that targets sclerostin, a protein that inhibits bone formation, leading to increased bone density and reduced fracture risk. This dual action of promoting bone growth and reducing bone breakdown makes it different from other osteoporosis treatments, which typically focus on just one of these aspects. ^{1 8 9 10 11}

Research Team

Christopher P Cardozo, M.D.

Principal Investigator

James J. Peters Veterans Affairs Medical Center

Eligibility Criteria

This trial is for men and women aged 18-55 with chronic spinal cord injury (SCI) who have low bone density at the distal femur. Participants must be more than three years post-injury, with motor-complete or incomplete SCI below C4. Exclusions include severe chronic diseases, recent high-dose steroid use, cancer history, certain endocrine disorders, pregnancy, alcohol abuse, and prior treatments for bone loss.

Inclusion Criteria

Your bone density at the lower part of your thigh is less than 1.0 grams per square centimeter.

Your injury has lasted for more than 3 years.

You have a spinal cord injury that affects your ability to move and feel below a certain level in your neck.

Exclusion Criteria

I have been on high-dose steroids for more than a week in the past year, not for spinal cord injury.

I do not have severe chronic diseases like COPD, heart failure, or kidney failure.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Romosozumab Treatment

Participants receive romosozumab treatment to increase bone formation and decrease bone resorption

12 months

Monthly visits for injections

Denosumab Treatment

Participants receive denosumab treatment to maintain or further increase bone mineral density

12 months

Injections at months 12 and 18

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Denosumab
• Placebo
• Romosozumab

Trial Overview The study tests Romosozumab's ability to increase bone density in people with chronic SCI followed by Denosumab to maintain or boost this effect. It's a two-group trial where one group gets Romosozumab then Denosumab while the control group receives a placebo then Denosumab over a total of 24 months.

Participant Groups

Group I: Romosozumab Treatment (baseline to month 11) Experimental Treatment 1 Intervention

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.

Group II: Denosumab (month 12 to month 24) Active Control 1 Intervention

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).

Group III: Placebo (baseline to month 12) Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Kessler Institute for Rehabilitation

Industry Sponsor

Trials

23

Recruited

1,100+

Findings from Research

Romosozumab significantly increases spine bone mineral density (BMD) after 12 months of treatment, with a 10.67% increase observed in a study of 262 patients, indicating its efficacy in treating spine osteoporosis.

The treatment was associated with a low incidence of new fractures (only five cases) and no fatal adverse events, highlighting its safety profile, especially in patients not previously treated with other osteoporosis medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early clinical effects, safety, and predictors of the effects of romosozumab treatment in osteoporosis patients: one-year study. Tominaga, A., Wada, K., Okazaki, K., et al.[2022]

Romosozumab significantly reduces the risk of fractures in postmenopausal women with osteoporosis, showing a 63% lower risk of new vertebral fractures and a 41% lower risk of hip fractures compared to other therapies, based on data from six randomized controlled trials involving over 5,600 participants.

The treatment also leads to substantial increases in bone mineral density (BMD) at key sites like the lumbar spine and hip, while demonstrating a good safety profile with no significant increase in adverse events compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. Liu, Y., Cao, Y., Zhang, S., et al.[2019]

Romosozumab significantly reduces the incidence of new vertebral fractures in postmenopausal women with osteoporosis after just 12 months of treatment, showing strong efficacy compared to both placebo and active bisphosphonate controls.

However, there is a concerning numerical increase in cardiovascular events associated with romosozumab, suggesting it should be used cautiously, especially in patients with a history of cardiovascular issues or high cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. Fixen, C., Tunoa, J.[2021]

In a study of 70 patients with severe osteoporosis, romosozumab significantly improved bone metabolism markers (TRACP 5b and P1NP) within 1-2 months of treatment, indicating its effectiveness in enhancing bone formation.

After 5-7 months of treatment, romosozumab led to a significant increase in bone density, specifically in the lumbar spine, demonstrating its potential as a dual-action therapy that both enhances bone formation and reduces bone resorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study. Inage, K., Orita, S., Eguchi, Y., et al.[2021]

Romosozumab significantly increases bone mineral density (BMD) in patients with osteoporosis, showing greater gains at the lumbar spine and hip compared to teriparatide after 12 months, making it an effective treatment option.

While romosozumab reduces fracture risk in high-risk postmenopausal women, it is associated with a higher incidence of serious cardiovascular events, so it should be avoided in patients with recent history of myocardial infarction or stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis. Nealy, KL., Harris, KB.[2021]

In a study involving 7180 postmenopausal women with osteoporosis, romosozumab significantly reduced the risk of clinical vertebral fractures (VFxs) by 83% compared to placebo over 12 months, with only 3 cases in the romosozumab group versus 17 in the placebo group.

Romosozumab works by inhibiting sclerostin, which increases bone formation and decreases bone resorption, leading to rapid improvements in bone density and strength, thereby reducing fracture risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of 1 Year of Romosozumab on the Incidence of Clinical Vertebral Fractures in Postmenopausal Women With Osteoporosis: Results From the FRAME Study. Geusens, P., Oates, M., Miyauchi, A., et al.[2020]

Romosozumab is a highly effective treatment for osteoporosis, functioning as a monoclonal antibody that inhibits sclerostin, leading to increased bone mineral density (BMD) and superior results compared to traditional treatments like bisphosphonates and PTH analogs.

While romosozumab shows significant benefits in bone density and fracture risk reduction, it carries a black box warning for patients with recent myocardial infarction or stroke, indicating a need for caution and further research on its cardiovascular safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Romosozumab in the Management of Osteoporosis: Focus on Patient Selection and Perspectives. Lim, SY., Bolster, MB.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Early clinical effects, safety, and predictors of the effects of romosozumab treatment in osteoporosis patients: one-year study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. [2021]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Time-Course Changes in Bone Metabolism Markers and Density in Patients with Osteoporosis Treated with Romosozumab: A Multicenter Retrospective Study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The effects of romosozumab combined with active vitamin D3 on fracture healing in ovariectomized rats. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Romosozumab: A first-in-class sclerostin inhibitor for osteoporosis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

The Effect of 1 Year of Romosozumab on the Incidence of Clinical Vertebral Fractures in Postmenopausal Women With Osteoporosis: Results From the FRAME Study. [2020]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Utility of Romosozumab in the Management of Osteoporosis: Focus on Patient Selection and Perspectives. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study. [2020]