Evaluation of Pharmacokinetics, Pharmacodynamics, Efficacy, Safety, and Immunogenicity of BP16 Compared to Denosumab in Post-Menopausal Osteoporosis Patients

The primary objective of this study is to demonstrate the therapeutic and **pharmacodynamic** equivalence between BP16 and EU-Prolia in women with post-menopausal osteoporosis. This will be assessed by evaluating the change in bone mineral density (BMD) at Week 52 and the area under the effect curve (AUEC) in serum C-telopeptide (sCTX) up to Week 26. Establishing equivalence in these parameters is clinically relevant as it may provide an alternative treatment option for managing post-menopausal osteoporosis, potentially improving patient outcomes and expanding therapeutic choices.

Secondary objectives include:

• Assessing and comparing the pharmacodynamics (PD) between BP16 and EU-Prolia.
• Evaluating and comparing other efficacy parameters between BP16 and EU-Prolia.
• Assessing and comparing the pharmacokinetic (PK) parameters between BP16 and EU-Prolia.
• Evaluating and comparing the safety profiles of BP16 and EU-Prolia.
• Assessing and comparing the immunogenicity between BP16 and EU-Prolia.

The clinical trial focuses on **post-menopausal osteoporosis** and involves a study population exclusively comprising post-menopausal women aged between 55 and 80 years. The participants are required to have a body weight ranging from 50 to 90 kg and must exhibit evidence of osteoporosis, specifically a lumbar spine absolute bone mineral density (BMD) corresponding to a T-score between -2.5 and -4.0. The trial does not include any male subjects or vulnerable populations. Participants were selected based on their ability to provide informed consent and comply with study procedures. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, parallel-group, multicenter study aimed at comparing the pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity of BP16 versus EU-Prolia in women with **post-menopausal osteoporosis**. The trial will span approximately 52 weeks, with an estimated end date of November 30, 2025. Participants will be randomly assigned to receive either BP16 or EU-Prolia, administered via **subcutaneous injection**. The primary endpoints include the percent change from baseline in lumbar spine bone mineral density (LS-BMD) at Week 52 and the area under the effect curve (AUEC) of serum C-telopeptide (sCTX) from Week 0 up to Week 26.

The study will commence with an inclusion (screening) visit, where eligibility will be assessed based on criteria such as age, body weight, and bone mineral density. Following successful screening, participants will undergo a series of study visits, including baseline, follow-up visits at Weeks 26 and 52, and an end-of-study visit. These visits will involve assessments of bone turnover markers, incidence of fractures, serum trough concentration of **denosumab**, and monitoring of adverse events. The study will also evaluate the incidence and titer of antidrug antibodies at specified intervals.

Participant involvement is expected to last for the duration of the trial, approximately 52 weeks. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results, contributing valuable data to the understanding and treatment of post-menopausal osteoporosis.

The clinical trial involves the administration of **Denosumab**, a monoclonal antibody used in the treatment of post-menopausal osteoporosis. Denosumab is provided in two forms: as a pre-filled syringe for subcutaneous injection and as a solution for infusion in a pre-filled syringe. The dosage for Denosumab is set at a maximum of 60 mg per administration, with a total maximum dose of 180 mg over the treatment period. The administration is conducted subcutaneously every 26 weeks, with a maximum treatment period of 52 weeks. The pre-filled syringe is made from type I glass with a stainless steel 27-gauge needle, equipped with a needle guard to ensure safety during administration.

BP16, a comparator product, is also utilized in the study. It is a solution for infusion in a pre-filled syringe, containing the active substance Denosumab. The dosage and administration schedule for BP16 are identical to those of Denosumab, with a maximum daily dose of 60 mg and a total maximum dose of 180 mg over 52 weeks. The solution is administered subcutaneously, and the pre-filled syringe is constructed from USP type-I glass tubing, ensuring sterility and absence of surface defects.

In addition to the experimental treatments, the study includes the administration of **Vitamin D3** (Colecalciferol) in the form of soft capsules. Each capsule contains 400 IU of Colecalciferol, with a maximum daily dose of 4000 IU and a total maximum dose of 2,296,000 IU over a treatment period of 82 weeks. The capsules are administered orally to support bone health and calcium absorption.

Furthermore, a combination of **Ascorbic Acid**, **Calcium Carbonate**, and **Calcium Lactate Gluconate** is provided as an auxiliary treatment. This combination is administered orally, with a maximum daily dose of 2 grams and a total maximum dose of 1148 grams over 82 weeks. The inclusion of these substances aims to enhance calcium levels and support overall bone health during the trial.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial is designed to evaluate the pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity of BP16 compared to EU-Prolia® in women with post-menopausal osteoporosis.

The efficacy of the clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include the percent change from baseline in lumbar spine bone mineral density (LS-BMD) at Week 52 and the area under the effect curve (AUEC) of serum C-telopeptide (sCTX) from Week 0 up to Week 26. These endpoints are designed to demonstrate therapeutic and pharmacodynamic equivalence between BP16 and EU-Prolia in women with post-menopausal osteoporosis.

Secondary endpoints will further evaluate efficacy by measuring the percent change in bone turnover markers, such as sCTX and P1NP, at Weeks 26, 52, and 78. Additionally, the percent change from baseline in LS-BMD at Weeks 26 and 78, as well as in total hip and femoral neck BMD at Weeks 26, 52, and 78, will be assessed. The incidence of fractures up to Weeks 52 and 78 will also be monitored. Serum trough concentration of **denosumab** at Weeks 26, 52, and 78 will be measured to provide further insights into the drug's pharmacokinetics.

Data collection will include physical examinations, vital signs, 12-lead ECGs, and laboratory parameters such as hematology, clinical chemistry, and urinalysis. The incidence and titer of antidrug antibodies to **denosumab** will be evaluated at multiple timepoints, including Weeks 0, 12, 26, 52, and 78, along with the incidence of neutralizing antibodies in all ADA-positive subjects. The incidence, nature, and severity of adverse events, including adverse drug reactions, will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.