comparative efficacy and safety study of rgb-14-p and prolia® in women with postmenopausal osteoporosis

Conditions: Postmenopausal Osteoporosis

Summary: 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).

Eligibility criteria:
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

Keywords: biosimilars prolia®