Romosozumab vs Denosumab for Osteoporosis After Spinal Cord Injury

Not currently recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two treatments, romosozumab and denosumab (also known as Prolia or Xgeva), to determine which better maintains bone mass in people with a spinal cord injury. Participants will receive either romosozumab followed by denosumab or just denosumab for a total of 24 months. The trial is ideal for individuals who have had a spinal cord injury within the last six months and are experiencing issues with bone strength around the knee. As a Phase 4 trial, the treatments have already received FDA approval and have proven effective, offering participants a chance to contribute to research that helps understand how these treatments benefit more patients.

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.

What is the safety track record for these treatments?

Research has shown that romosozumab can help build and strengthen bones by increasing bone growth and reducing bone loss. Most people tolerate romosozumab well, though some experience side effects like joint pain or a risk of heart problems.

Denosumab is another treatment for bone loss and has been extensively studied. It is generally well-tolerated, but some individuals may experience side effects such as back pain or skin issues. Notably, the FDA has already approved denosumab for other uses, which can reassure its safety.

Both treatments have been tested in many individuals, and serious side effects are uncommon. However, those considering joining a trial should discuss any personal health concerns with their doctor. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they offer new ways to tackle osteoporosis after spinal cord injury (SCI). Romosozumab works differently from traditional treatments by targeting a protein called sclerostin, which helps to build bone density more effectively. Denosumab, on the other hand, prevents bone breakdown by inhibiting a protein involved in bone resorption. The combination of these mechanisms could potentially provide a more comprehensive approach to managing bone loss in SCI patients compared to current options.

What evidence suggests that this trial's treatments could be effective for osteoporosis after spinal cord injury?

Research has shown that both denosumab and romosozumab effectively improve bone health. In this trial, participants will divide into two groups. One group will receive denosumab, which maintains bone strength at the knee in people with spinal cord injuries and increases bone mass in the lower spine and thigh bone. The other group will initially receive romosozumab, which boosts bone density and reduces pain, especially in the spine, by encouraging new bone growth, followed by denosumab. Together, these treatments are expected to maintain and improve bone strength in those with spinal cord injuries. ^{6 7 8 9 10}

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

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 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 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. 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26423406/

Denosumab increases sublesional bone mass in ... Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI.

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

Pharmacological approaches for bone health in persons ... Denosumab has recently been reported to prevent bone loss in persons with acute SCI but should be continued for an as yet indeterminate time because ...

4. 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.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05101018

NCT05101018 | Treatment With Romosozumab Versus ... The objective of the proposed work is to determine whether administration for 12 months of romosozumab followed by 12 months of denosumab will maintain bone ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11345130/

Treatment effects, adverse outcomes and cardiovascular ... Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK585139/

Romosozumab - StatPearls - NCBI Bookshelf - NIH Monthly treatment with romosozumab for 1 year increases bone mineral at the hip, but not the knee, in women with chronic spinal cord injury. JBMR Plus. 2024 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04232657

Romosozumab to Improve Bone Mineral Density and ... 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 ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1708322

Romosozumab or Alendronate for Fracture Prevention in ... Romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone.

10. academic.oup.com academic.oup.com/jbmrplus/article/8/7/ziae077/7689629

Monthly treatment with romosozumab for 1 year increases ... Monthly treatment with romosozumab for 1 year increases bone mineral at the hip, but not the knee, in women with chronic spinal cord injury Open Access. Laura E ...