Denosumab for Osteoporosis

Recruiting at 38 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

392 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Denosumab for osteoporosis?

Denosumab has been shown to significantly reduce the risk of fractures in women with postmenopausal osteoporosis by increasing bone mineral density and decreasing bone resorption. Clinical studies have demonstrated its effectiveness in reducing vertebral, hip, and nonvertebral fractures with an acceptable rate of side effects. ^{1 2 3 4 5}

Is Denosumab safe for humans?

Denosumab has been generally well tolerated in studies lasting up to 10 years, but some side effects have been noted, such as back pain, pain in extremities, and musculoskeletal pain. Rare but serious side effects include osteonecrosis of the jaw (a condition where the jawbone starts to die) and atypical femur fractures. There is also a potential risk of multiple vertebral fractures after stopping the drug, so careful management is needed. ^{6 7 8 9 10}

How is the drug denosumab different from other osteoporosis treatments?

Denosumab is unique because it is a fully human monoclonal antibody that targets RANKL, a protein involved in bone breakdown, and is administered as a subcutaneous injection every six months, unlike other treatments that may require more frequent dosing or different administration routes. ^{1 3 5 6 11}

What is the purpose of this trial?

this comparative clinical study is designed to demonstrate that LY06006 and EU-Prolia have no clinically meaningful differences in clinical efficacy, pharmacodynamic (PD), safety, PK, and immunogenicity in postmenopausal women with osteoporosis.

Research Team

Joe Tai

Principal Investigator

Luye Pharma Group Ltd.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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, 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]

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, 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]

References

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

Quantitative pharmacology of denosumab in patients with bone metastases from solid tumors. [2015]

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

Denosumab: What's new? [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. [2021]

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

Update on denosumab treatment in postmenopausal women with osteoporosis. [2023]

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

Denosumab: a case of MRONJ with resolution. [2018]

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States 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. [2018]

8. Italy pubmed.ncbi.nlm.nih.gov

Interstitial Lung Disease in a Patient Treated with Denosumab. [2022]

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

Denosumab: A Review in Postmenopausal Osteoporosis. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

[Treatment of osteoporosis with Denosumab]. [2015]

11. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and pharmacodynamics of denosumab in patients with advanced solid tumours and bone metastases: a systematic review. [2022]