Romosozumab vs Denosumab for Osteoporosis After Spinal Cord Injury

Recruiting at 1 trial location

Overseen By Christopher P Cardozo, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: James J. Peters Veterans Affairs Medical Center

Must not be taking: Bisphosphonates, Corticosteroids

Disqualifiers: Coronary heart disease, Stroke, Bone cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 6

Duration: 24 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing two ways to use medications that help keep bones strong in people with recent spinal cord injuries. One method uses a medication that helps build new bone for a period and then switches to another medication that prevents bone loss for another period. The other method uses only the medication that prevents bone loss for a longer period.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking medications for osteoporosis other than calcium and vitamin D, or certain corticosteroids, you may need to stop those. It's best to discuss your specific medications with the study staff.

Is Romosozumab safe for use in humans?

Romosozumab has been shown to significantly reduce the risk of new vertebral fractures in postmenopausal women with osteoporosis, with a low incidence of clinical vertebral fractures reported. However, there are concerns about its effectiveness in preventing fractures after discontinuation of denosumab, as seen in a case where a patient experienced multiple fractures after switching to romosozumab. ^{1 2 3 4 5}

How is the drug Romosozumab unique for treating osteoporosis after spinal cord injury?

Romosozumab is unique because it is a monoclonal antibody that both increases bone formation and decreases bone resorption, which helps to quickly increase bone mass and reduce fracture risk. It is particularly effective in increasing bone mineral density in the spine, especially in patients who have not been previously treated with other osteoporosis medications. ^{1 4 6 7 8}

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

Research shows that Romosozumab can significantly increase bone density and reduce fracture risk in postmenopausal women with osteoporosis. It is effective in maintaining bone density gains achieved with Denosumab and further increasing bone density in the spine. ^{1 2 3 4 6}

Who Is on the Research Team?

Steven Kirshblum, MD

Principal Investigator

Kessler Institute for Rehabilitation

Are You a Good Fit for This Trial?

This trial is for men and premenopausal women aged 18-55 with a recent traumatic spinal cord injury (SCI) between C4-L2, who have not taken certain osteoporosis medications other than calcium and vitamin D. Participants must have a specific bone density level above the knee and cannot have conditions like chronic alcohol abuse, cancer history, severe chronic diseases, or be pregnant.

Inclusion Criteria

Your bone density near your knee needs to be within a safe range, as determined by the study staff.

You have had a spinal cord injury for less than 6 months.

I have a spinal cord injury between C4 and L2, with some level of paralysis.

Exclusion Criteria

I have a condition affecting my hormone glands, like an overactive thyroid or Cushing's.

I have bone growth outside of the skeleton in the knee end of my thigh bone.

I have been diagnosed with cancer or have a history of it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive romosozumab for 12 months followed by denosumab for 12 months, or denosumab alone for 24 months

24 months

Monthly visits for romosozumab, every 6 months for denosumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab
• Romosozumab

Trial Overview The study tests if treating patients first with Romosozumab for 12 months followed by Denosumab for another year helps maintain bone mass at the knee better than just using Denosumab alone for two years in individuals with subacute SCI.

How Is the Trial Designed?

Group I: Romosozumab Baseline to Month 11 followed by Denosumab Month 12 to Month 24 Experimental Treatment 2 Interventions

Of the forty (40) individuals with subacute spinal cord injury (SCI) enrolled in this study, twenty (20) participants will be randomly selected to receive romosozumab (210mg SQ) once a month for 12 months. After 12 months the same twenty (20) individuals will receive denosumab (60mg SQ) at month 12 and 18.

Group II: Denosumab Baseline to Month 24 Active Control 1 Intervention

Of the forty (40) individuals with subacute spinal cord injury (SCI) enrolled in this study, twenty (20) participants will be randomly selected to receive denosumab (60 mg SQ) at baseline and 6, 12, and 18 months.

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Prolia for:

• Osteoporosis in postmenopausal women
• Bone loss associated with hormone ablation therapy for prostate cancer
• Bone loss associated with hormone ablation therapy for breast cancer

Approved in United States as Prolia for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture
• Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center

Lead Sponsor

Trials

59

Recruited

2,900+

Kessler Institute for Rehabilitation

Industry Sponsor

Trials

23

Recruited

1,100+

Published Research Related to This Trial

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]

Romosozumab treatment significantly increased bone mineral density (BMD) in the lumbar spine compared to denosumab, with increases of 4.9% and 5.2% at 3 and 6 months, respectively, versus 2.3% and 3.2% for denosumab.

Despite the improvement in BMD, romosozumab did not significantly affect disease activity in rheumatoid arthritis (RA) patients over the 6-month study period, indicating that while it may help with bone health, it does not impact RA symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of romosozumab or denosumab treatment on the bone mineral density and disease activity for 6 months in patients with rheumatoid arthritis with severe osteoporosis: An open-label, randomized, pilot study. Mochizuki, T., Yano, K., Ikari, K., et al.[2022]

Citations

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

Skeletal responses to romosozumab after 12 months of denosumab. [2021]

2. 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]

3. 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]

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

Romosozumab was not effective in preventing multiple spontaneous clinical vertebral fractures after denosumab discontinuation: A case report. [2020]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of romosozumab or denosumab treatment on the bone mineral density and disease activity for 6 months in patients with rheumatoid arthritis with severe osteoporosis: An open-label, randomized, pilot study. [2022]

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

Romosozumab efficacy and safety in European patients enrolled in the FRAME trial. [2022]

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

Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension. [2021]