Comparative Efficacy of Teriparatide and Alendronate in Preventing Vertebral Fractures in Women with Bone Fragility: A 52-Week Randomized Study

The primary objective of this study is to evaluate the **efficacy** of biosimilar teriparatide compared to alendronate in reducing the incidence of new morphometric vertebral fractures and/or worsening of previous fractures in women over 65 years of age with recent clinical vertebral fracture or hip fracture caused by bone fragility after 52 weeks of treatment. This is clinically relevant as it addresses the prevention of further fractures in a population at high risk due to bone fragility, potentially improving patient outcomes and reducing healthcare burdens associated with fracture management.

Secondary objectives include evaluating differences between patients treated with biosimilar teriparatide and those treated with alendronate in several areas: - Incidence of new morphometric vertebral fractures and/or worsening of previous fractures at 26 weeks of treatment. - Incidence of new clinical vertebral fractures at 26 and 52 weeks. - Incidence of moderate and severe vertebral fractures (grades 2 and 3) at 26 and 52 weeks. - Incidence of multiple vertebral fractures at 26 and 52 weeks. - Incidence of non-vertebral fractures at 26 and 52 weeks. - Incidence of major non-vertebral fractures (proximal humerus, distal radius, and proximal femur) at 26 and 52 weeks. - Changes in **Bone Mineral Density** (BMD) at 52 weeks. - Changes in **Trabecular Bone Score** (TBS) at 52 weeks. - Reduction in spinal pain, using a visual analogue scale (VAS) at 10, 26, and 52 weeks. - Improvement in quality of life, using the EQ-5D questionnaire at 26 and 52 weeks. - Evaluation of patient adherence to teriparatide and alendronate by the delivery of their used cartridges or ampoules respectively, at visits 2, 3, and 4 (approximately 10, 26, and 52 weeks). - Safety, assessed through adverse events.

The clinical trial involves a study population consisting exclusively of **women** over the age of 65, who have experienced a recent clinical vertebral fragility fracture or hip fragility fracture within the past three months. The trial focuses on the **prevention of new morphometric vertebral fractures** and/or the worsening of previous vertebral fractures. Participants were selected based on their recent fracture history, confirmed by X-ray, and their consent to participate in the study. The trial does not include male subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The study aims to evaluate the efficacy of biosimilar teriparatide compared to alendronate over a 52-week treatment period.

The clinical trial is a **randomized**, double-blind, controlled study designed to evaluate the efficacy of biosimilar **teriparatide** compared to **alendronate** in reducing the incidence of new morphometric vertebral fractures and/or worsening of previous fractures in women over 65 years of age with recent clinical vertebral fracture or hip fracture caused by bone fragility. The trial is set to last for 52 weeks, with the primary endpoint being the percentage of patients experiencing at least one new morphometric vertebral fracture or an increase in the severity of a known vertebral fracture during the study period. The Genant semi-quantitative method will be employed for the diagnosis and grading of vertebral fractures using thoracic and lumbar radiographs.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, recent fracture history, and informed consent. Follow-up visits will be scheduled at regular intervals to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will occur at the conclusion of the 52-week period, where final assessments will be conducted to evaluate the primary and secondary endpoints, including changes in bone mineral density, vertebral pain, and quality of life.

The expected length of participant involvement is approximately one year, aligning with the overall trial duration. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide valuable insights into the comparative effectiveness of the two treatments in preventing fractures in a high-risk population.

The clinical trial involves the administration of **Teriparatide**, marketed under the name Terrosa, which is a **solution for injection** in a pre-filled pen. The active substance, teriparatide, is a protein-based compound. The pharmaceutical form is a solution for injection, and it is administered subcutaneously. Each pre-filled pen contains 20 micrograms of teriparatide per 80 microliters. The maximum daily dose is 20 micrograms, and the treatment period is limited to 24 months. The product is manufactured by Gedeon Richter PLC and is authorized for use in the European Union under the marketing authorization number EU/1/16/1159/004. Participant compliance with the dosing schedule will be monitored throughout the study.

The comparator treatment in this study is **Alendronate Sodium Trihydrate**, marketed as Acido Alendronico Aurobindo. This medication is provided in the form of **tablets** and is administered orally. Each tablet contains 70 mg of alendronate sodium trihydrate. The maximum total dose is 70 mg, with a maximum daily dose of 10 mg, and the treatment period extends up to 60 months. This chemical-based compound is produced by Aurobindo Pharma (Italia) S.R.L. and is authorized in Italy with the marketing authorization number 041256304. The study will ensure adherence to the dosing regimen through regular monitoring of participant compliance.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints over a 52-week period. The primary endpoint is the percentage of patients experiencing at least one new morphometric vertebral fracture or an increase in the severity of a known vertebral fracture. The Genant semi-quantitative method will be employed for the diagnosis and grading of vertebral fractures using thoracic and lumbar radiographs.

Secondary endpoints include the occurrence of new morphometric vertebral fractures, new clinical vertebral fractures, new non-vertebral fractures, and new major non-vertebral fractures. Additionally, changes in bone mineral density (BMD) from baseline, vertebral pain assessed through the Visual Analogue Scale (VAS) for pain, therapeutic adherence, and quality of life measured by the EQ-5D questionnaire will be evaluated. The frequency of adverse events (AEs), serious adverse events (SAEs), and AEs leading to treatment discontinuation will also be monitored. These assessments will provide a comprehensive evaluation of the efficacy of biosimilar **teriparatide** compared to alendronate in reducing fracture risk in the target population.