Romosozumab for Osteoporosis in Chronic Spinal Cord Injury

(Chronic Romo Trial)

Not currently recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for osteoporosis in individuals with long-term spinal cord injuries. It tests romosozumab, a medication that may help build and maintain bone strength, followed by denosumab, which prevents bone loss. Participants will be randomly divided into two groups: one receiving romosozumab and the other a placebo for the first year. In the second year, both groups will receive denosumab. Ideal participants have had a spinal cord injury for more than three years and low bone density in the thigh area. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that romosozumab has promising safety results from past studies. In one study, people with chronic spinal cord injury who took romosozumab monthly for a year generally tolerated it well. There were no major reports of severe side effects, though some experienced mild reactions like joint pain or headaches. Another study confirmed long-term safety, indicating that romosozumab can be used safely over extended periods.

Denosumab has been well-studied and is widely used for osteoporosis. In clinical trials with women who have low bone density, denosumab was generally well-tolerated. Most side effects were mild, and serious ones were rare. Common side effects included back pain and a higher chance of infections. The FDA has approved denosumab for treating osteoporosis, further supporting its safety.

Both treatments have undergone extensive testing, and current evidence suggests they are safe for similar groups of people. However, as with any treatment, individual responses may vary, and discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for osteoporosis?

Unlike the standard treatments for osteoporosis, which often include bisphosphonates like alendronate or antiresorptive agents like denosumab, romosozumab works by a unique mechanism. Romosozumab is a monoclonal antibody that not only inhibits bone resorption but also stimulates bone formation, offering a dual-action approach that could be more effective for individuals with chronic spinal cord injury. Researchers are excited about romosozumab because it targets the sclerostin protein, potentially leading to greater increases in bone mineral density compared to traditional therapies. Additionally, its monthly subcutaneous injection format is convenient and may improve patient adherence compared to treatments that require more frequent dosing.

What evidence suggests that romosozumab might be an effective treatment for osteoporosis in chronic spinal cord injury?

Research has shown that romosozumab, which participants in this trial may receive, can improve bone strength in people with spinal cord injuries. It promotes bone growth and slows down bone breakdown. Studies indicate that taking romosozumab once a month for a year can significantly increase bone strength and reduce the risk of fractures, particularly in the hip. After completing romosozumab treatment, participants will receive denosumab, which helps maintain or even enhance bone strength. Denosumab effectively maintains bone strength in various situations, including after a spinal cord injury. This trial's combination approach aims to combat bone loss by first building bone with romosozumab and then maintaining it with denosumab. ^{1 2 6 7 8}

Who Is on the Research Team?

Christopher P Cardozo, M.D.

Principal Investigator

James J. Peters Veterans Affairs Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7587457/

Administration of Denosumab Preserves Bone Mineral ... Administration of denosumab preserves bone mineral density at the knee in persons with subacute spinal cord injury: findings from a randomized clinical trial.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01983475

Denosumab Administration After Spinal Cord Injury Denosumab is a relative new, highly potent anti-resorptive agent that has proven efficacy in postmenopausal osteoporosis to improve bone mass and in solid tumor ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10759830/

Student Competition (Knowledge Generation) ID 1985735 ... This retrospective cohort study aims to evaluate the effectiveness of Denosumab injections with dietary calcium and vitamin D supplements on proximaltibia bone ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1471489221001235

Pharmacological approaches for bone health in persons ... The most effective therapeutic approach would prevent loss of bone mass and architecture shortly after paralysis.

5. scielo.isciii.es scielo.isciii.es/pdf/romm/v14n2/en_1889-836X-romm-14-2-0088.pdf

Effect of treatment with denosumab for 24 months in ... Conclusions: Treatment with denosumab during 24 months increases lumbar and femoral BMD and decreases BTMs in patients with recent SCI.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3264422/

Safety and tolerability of denosumab for the treatment ... In clinical trials of women with osteoporosis and low bone mineral density, denosumab has been well tolerated, with overall rates of adverse events and serious ...

7. fda.gov fda.gov/drugs/news-events-human-drugs/fda-approves-first-interchangeable-biosimilars-prolia-and-xgeva-treat-certain-types-osteoporosis-and

FDA approves first interchangeable biosimilars to Prolia ... FDA approves first interchangeable biosimilars to Prolia and Xgeva to treat certain types of osteoporosis and prevent bone events in cancer.

8. prolia.com prolia.com/proven-results/safety-information

Side Effects of Prolia® (denosumab) This 3-year clinical study tested the safety of Prolia® in over 7700 women with postmenopausal osteoporosis aged 60 to 90 years. Approximately half of the ...