Denosumab for Osteoporosis

Not currently recruiting at 45 trial locations

Overseen By Maggie Wang, Master

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Luye Pharma Group Ltd.

Must not be taking: Bisphosphonates, HRT, Glucocorticoids, others

Disqualifiers: Fractures, Bone diseases, Malignancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called denosumab (also known as Prolia or Xgeva) to determine if it helps postmenopausal women with osteoporosis, a condition where bones weaken and are more prone to fractures. The research compares two versions of this treatment to ensure they work the same and are safe. Women who have gone through menopause and have been diagnosed with osteoporosis might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment option.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that can affect bone density, such as osteoporosis treatments (other than calcium and vitamin D supplements), certain hormone therapies, and some other specific drugs. It's best to discuss your current medications with the study team to see if any need to be stopped before participating.

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

Research has shown that both LY06006 and EU-Prolia, types of denosumab, are generally well-tolerated. In previous studies, LY06006 demonstrated a safety profile similar to a placebo when tested in postmenopausal women at high risk for osteoporosis, indicating that side effects were not significantly different from those receiving a non-active treatment.

Other studies have found that denosumab, the active ingredient in both LY06006 and EU-Prolia, effectively reduces bone loss and increases bone strength. This is crucial as it helps lower the risk of fractures in people with osteoporosis.

The current trial is in phase 3, which typically indicates that earlier phases have already tested the treatment for safety. Serious side effects are not expected to be common. However, as with any medical treatment, some risks may exist, and those considering participation should discuss potential side effects with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for osteoporosis, such as bisphosphonates, Denosumab offers a unique approach by targeting a protein called RANKL, which plays a crucial role in bone breakdown. This mechanism helps to prevent bone loss more directly. Researchers are excited about Denosumab because it is administered as a subcutaneous injection every six months, which can be more convenient compared to daily or weekly oral medications. This could lead to better adherence and potentially improved outcomes for patients managing osteoporosis.

What evidence suggests that this trial's treatments could be effective for osteoporosis?

Research has shown that denosumab effectively treats osteoporosis. In one study, women taking denosumab had a 10.5% risk of major bone fractures, compared to 17.2% for those taking alendronate, indicating that denosumab reduces fracture risk. Another study found that denosumab lowered the risk of hip fractures by 36% in men with osteoporosis. It also increases bone mineral density (BMD), which is crucial for strong bones. Overall, denosumab has been shown to reduce the chances of bone fractures and improve bone health. Participants in this trial will receive either the experimental treatment LY06006 or the active comparator EU Prolia, both involving denosumab, to further evaluate its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Joe Tai

Principal Investigator

Luye Pharma Group Ltd.

Are You a Good Fit for This Trial?

This trial is for ambulatory postmenopausal women aged 60-90 with osteoporosis, having a T-score of ≤ -2.5 and ≥ -4.0 at the lumbar spine. Participants must weigh between 50 kg and 90 kg, have had no menstrual period for at least 12 months or undergone bilateral oophorectomy, and be able to give informed consent.

Inclusion Criteria

Serum FSH test can be done at the Screening Visit in case of uncertainty

I am a woman who has gone through menopause and can walk.

My weight is between 50 kg and 90 kg.

Exclusion Criteria

I am currently on treatment for osteoporosis.

I have a history of bone disease.

I currently have a fracture that is healing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Main Period

Participants receive either LY06006 or EU-Prolia subcutaneously at Baseline and Month 6, with daily supplements of calcium and vitamin D

12 months

Visits at Baseline, Months 0.5, 1, 2, 3, 6, 9, and 12

Transition Period

Participants are re-randomized to continue or switch treatments, with blood sampling for PD, safety, PK, and immunogenicity

6 months

Visits at Months 15 and 18

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab

Trial Overview The study tests whether LY06006 has similar effects as EU-Prolia in treating osteoporosis in postmenopausal women by comparing their efficacy, safety, pharmacokinetics (PK), and immune response.

How Is the Trial Designed?

Group I: LY06006 Experimental Treatment 1 Intervention

to be administered 2 doses to the patients at the main treatment period and 1 dose at the transition period.

Group II: EU Prolia Active Control 1 Intervention

to be administered 2 doses to the patients at the main treatment period and 1 dose at the transition period.

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?

Luye Pharma Group Ltd.

Lead Sponsor

Trials

67

Recruited

9,900+

Liu Dian Bo

Luye Pharma Group Ltd.

Chief Executive Officer since 2003

Bachelor's degree in Economics from Fudan University

Cai Jianming

Luye Pharma Group Ltd.

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

Denosumab, a drug used to prevent bone loss, was linked to a non-healing area in the lower jaw after a tooth extraction, highlighting a potential complication associated with its use.

After stopping denosumab, the non-healing area healed successfully, suggesting that discontinuation of the drug may be necessary to allow for healing in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab: a case of MRONJ with resolution. Lyttle, CV., Patterson, H.[2018]

Denosumab, a monoclonal antibody that inhibits RANKL, shows consistent pharmacokinetics across a large population of 1,076 subjects, including both healthy individuals and cancer patients, indicating its effectiveness in preventing osteoclast activation and survival.

The study found that after administering denosumab, over 95% of patients achieved more than 97% RANKL occupancy, suggesting that dosage adjustments based on body weight, age, race, or tumor type are unnecessary for patients with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Gibiansky, L., Sutjandra, L., Doshi, S., et al.[2021]

Denosumab, a monoclonal antibody used to treat skeletal-related events in advanced cancer patients, shows dose-dependent pharmacokinetics, meaning its absorption and effects vary with the dose given, particularly at doses below 60 mg.

In patients with solid tumors and bone metastases, denosumab effectively reduces bone turnover markers quickly, and its pharmacokinetics and pharmacodynamics remain consistent across different tumor types and cancer treatments, indicating its broad applicability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and pharmacodynamics of denosumab in patients with advanced solid tumours and bone metastases: a systematic review. Sohn, W., Simiens, MA., Jaeger, K., et al.[2022]

Denosumab, a medication commonly used to treat osteoporosis, has known side effects like atypical femur fractures and osteonecrosis of the jaw, but this case report highlights a potential link to interstitial lung disease (ILD) as well.

While this is the first reported case of ILD possibly related to denosumab, it does not establish a direct cause-and-effect relationship, but it suggests that healthcare providers should consider denosumab exposure in patients presenting with ILD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial Lung Disease in a Patient Treated with Denosumab. Ruiz, AC., Carrascosa, MF., Concha, ST., et al.[2022]

Denosumab is a novel antiresorptive drug approved in the UK for preventing osteoporotic fractures in postmenopausal women and for managing skeletal-related events in patients with bone metastases.

There is a risk of osteonecrosis of the jaw (ARONJ) associated with denosumab, which dental professionals need to consider when advising patients undergoing dental treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab, an Alternative to Bisphosphonates but also Associated with Osteonecrosis of the Jaw--What is the Risk?. Sidhu, HK.[2018]

Denosumab (XGEVA®) is a monoclonal antibody that effectively inhibits bone resorption by preventing the activation of osteoclasts, making it a targeted treatment for patients with bone metastases.

In Phase 3 clinical studies, denosumab was found to be superior to zoledronic acid in delaying skeletal-related events (SREs) by a median of 8.2 months, suggesting it may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative pharmacology of denosumab in patients with bone metastases from solid tumors. Perez Ruixo, JJ., Doshi, S., Sohn, W., et al.[2015]

Denosumab, a monoclonal antibody that targets RANKL, significantly reduces the risk of fractures in postmenopausal women with osteoporosis, showing a 68% reduction in new vertebral fractures and a 40% reduction in hip fractures over a 3-year trial.

Long-term treatment with denosumab did not show increasing trends in adverse events, indicating that its safety profile remains stable over 6 years, even when comparing data from initial placebo recipients who later received the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Observations With 3 Years of Denosumab Exposure: Comparison Between Subjects Who Received Denosumab During the Randomized FREEDOM Trial and Subjects Who Crossed Over to Denosumab During the FREEDOM Extension. Watts, NB., Brown, JP., Papapoulos, S., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39777487/

Denosumab and clinical outcomes among men with ... This real-world study shows direct evidence of fracture risk reduction among men with osteoporosis (36% of hip fracture reduction with denosumab) ...

2. e-enm.org e-enm.org/journal/view.php?number=2567

Long-Term Efficacy and Safety of Denosumab Although data up to a decade confirmed sustained BMD gains with denosumab, unlike other anti-resorptive agents, which typically plateau, the ...

3. prolia.com prolia.com/proven-results/real-world-study

Real-World Study Results | Prolia® (denosumab) The overall risk of major osteoporotic fracture was 10.5% for women taking Prolia® compared to 17.2% for women who took alendronate. Major osteoporotic ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa0809493

Denosumab for Fracture Prevention in Osteoporosis Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women ...

5. bmcmusculoskeletdisord.biomedcentral.com bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-025-08688-8

Efficacy of denosumab for osteoporosis in RA patients The data revealed a significant improvement in BMD, joint erosion scores, and joint narrowing scores in patients treated with denosumab compared ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9240259/

A Randomized Controlled Dose-Escalation Study of ... It has been proved that denosumab reduced bone resorption and increased BMD, which are associated with a significant reduction in the risk of osteoporosis ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05060406

A Study to Evaluate the Efficacy and Safety of LY06006 ... Primary Objective: To evaluate the efficacy of LY06006 in the treatment of postmenopausal women with osteoporosis at high risk for fracture. Secondary ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2214031X22000675

Denosumab biosimilar (LY06006) in Chinese ... In conclusion, compared with the placebo, LY06006 has similar safety in the treatment of osteoporosis in postmenopausal women with a high risk ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05853354

Comparative Efficacy, Safety, PK, and Immunogenicity Study this comparative clinical study is designed to demonstrate that LY06006 and EU-Prolia have no clinically meaningful differences in clinical efficacy, ...

10. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-ly06006-and-denosumab-for-postmenopausal-women-with-osteoporosis/

Study on the Effectiveness and Safety of LY06006 ... This study investigates the effectiveness and safety of the active substance denosumab, present in treatments LY06006 and EU-Prolia, for postmenopausal ...