Comparative Efficacy and Safety Study of RGB-14-P and Prolia® in Women With Postmenopausal Osteoporosis

A Randomised, Double Blind, Multicentre Phase III Study to Assess the Efficacy and Safety of RGB-14-P Compared to Prolia® in Women With Postmenopausal Osteoporosis

This study will be conducted to assess the efficacy, pharmacodynamic (PD), safety, tolerability, and immunogenicity of RGB -14- P compared to US-licensed Prolia® in participants with postmenopausal osteoporosis, in a comparative manner.

This is a randomized, double-blind, multicentre, multiple fixed-dose, 2-arm parallel-group study that includes 2 periods as:

1. Main period (52 weeks), consists of Treatment Period 1 (26 weeks) and Treatment Period 2 (26 weeks). On Day 1 of Treatment Period 1, prior to dosing, participants will be randomized in a 1:1 ratio to receive either RGB-14-P or Prolia®.
2. Transition Period: consists of Treatment Period 3 (26 weeks). On Day 1 of Treatment Period 3 (Week 52), a subset of participants who received Prolia® during the Main Period will be re-randomized 1:1 to receive either a dose RGB-14-P or Prolia® in a double-blinded manner. A subset of participants continuing in the Transition Period who received RGB-14-P during the Main Period will continue to receive a dose of RGB-14- P but will also follow the randomization procedure to maintain blinding.

All participants will receive the study drugs on 2 occasions (Weeks 0 and 26), on Day 1 of Treatment Periods 1 and 2. Participants continuing to the Transition Period will receive the study drugs on a third-occasion (Week 52), Day 1 of Treatment Period 3. One Treatment Period will take 6 months (26 weeks, 183 days).

Inclusion Criteria:

• Participant is an ambulatory postmenopausal woman, diagnosed with osteoporosis, able to walk, and not bedridden
• Participant has an absolute BMD consistent with T score ≤ 2.5 and ≥ 4.0 at the lumbar spine as measured by dual-energy X-ray absorptiometry (DXA) during the Screening Period and at least 2 lumbar vertebrae (from L1 to L4) must be evaluable by DXA
• Participant has body weight ≥ 50 and ≤ 90 kg at the Screening Period

Participants must meet the following criteria to be enrolled in the Transition Period:

- Have been enrolled, received both doses of the test drug, and completed the scheduled Main Period (up to Week 52) of the RGB-14-101 study

Exclusion Criteria:

• Participant has a history and/or presence of a severe or more than two moderate vertebral fractures as determined by central reading of lateral spine X-ray during the Screening Period
• Participant has a history and/or presence of hip fracture
• Participant has a history and/or presence of atypical femur fracture
• Participant presents with an active healing fracture
• Participant has a bilateral hip replacement (unilateral is allowed if the other hip is evaluable with DXA)
• Participant has a vitamin D deficiency
• Participant has hypocalcaemia or hypercalcemia at the Screening Period
• Participant has a history and/or presence of bone metastases, renal osteodystrophy, osteomyelitis, any metabolic, endocrine or traumatic bone disease
• Participant has a current uncontrolled status of hypothyroidism or hyperthyroidism
• Participant has a history (within 5 years prior to Screening) and/or current hypoparathyroidism or hyperparathyroidism
• Participant has malignancy within 5 years before Screening
• Participant has a history and/or presence of significant cardiac disease
• Participant has a known intolerance or malabsorption of calcium or vitamin D supplements
• Participant shows contraindications to denosumab therapy (e.g., hypocalcaemia), or calcium or vitamin D supplementation before starting test drug administration
• Participant has a latex allergy
• Participant has a history and/or presence of osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures
• Participant has history and/or presence of osteonecrosis of the external auditory canal
• Participant requiring ongoing use of any osteoporosis treatment
• Participant has previously received denosumab or biosimilar denosumab
• Participant has weight or girth measurements which may preclude accurate DXA measurements
• Participant has an active infection, including, but not limited to severe acute respiratory syndrome coronavirus-2, hepatis B, hepatitis C and human immunodeficiency virus infections during the Screening Period