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

Study Overview
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Brief Summary
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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.

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

Official Title
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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

Conditions
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Postmenopausal Osteoporosis

Intervention / Treatment
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* Drug: RGB-14-P
* Drug: Prolia®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RGB-14-P (Main period)<br>Randomized participants will receive subcutaneous (SC) injection of RGB-14-P, on Day 1 of Treatment periods 1 and 2. | Drug: RGB-14-P<br>* Participants will receive RGB-14-P into the thigh, abdomen, or upper arm as per the arm assigned.<br>|
| Active Comparator: Prolia® (Main period)<br>Randomized participants will receive SC injection of Prolia®, on Day 1 of Treatment periods 1 and 2. | Drug: Prolia®<br>* Participants will receive Prolia® into the thigh, abdomen, or upper arm as per the arm assigned.<br>|
| Experimental: RGB-14-P (Transition period)<br>Re-randomized participants will receive SC injection of RGB-14-P, on Day 1 of Treatment period 3. | Drug: RGB-14-P<br>* Participants will receive RGB-14-P into the thigh, abdomen, or upper arm as per the arm assigned.<br>|
| Active Comparator: Prolia® (Transition period)<br>Re-randomized participants will receive SC injection of Prolia®, on Day 1 of Treatment period 3. | Drug: Prolia®<br>* Participants will receive Prolia® into the thigh, abdomen, or upper arm as per the arm assigned.<br>|
| Experimental: RGB-14-P (Continued till transition period)<br>Randomized participants will continue to receive SC injection of RGB-14-P from the main period till Day 1 of Treatment period 3. | Drug: RGB-14-P<br>* Participants will receive RGB-14-P into the thigh, abdomen, or upper arm as per the arm assigned.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in lumbar spine bone mineral density (BMD) | Efficacy and effect similarity of RGB-14- P with US-licensed Prolia® on BMD at the lumbar spine at Week 52 will be determined in female participants with postmenopausal osteoporosis. | Baseline, Week 52 | 
| Area under the effective curve after the first dose until Day 183 of percent change from baseline in serum type I collagen C-telopeptide up to month 6 (AUEC of %CfB in sCTX00-m6) until Week 26 | Similar pharmacodynamics (AUEC of %CfB in sCTX) of RGB-14-P with US-licensed Prolia® in female participants will be demonstrated with postmenopausal osteoporosis. | Baseline, until Week 26 (Predose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in total hip BMD | Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis. | Baseline, Weeks 26, 52 and 78 | 
| Percentage change from baseline in lumbar spine BMD | Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis. | Baseline, Weeks 26 and 78 | 
| Percentage change from baseline in femoral neck BMD | Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis. | Baseline, Weeks 26, 52 and 78 | 
| Vertebral fragility fracture incidence | Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis. | Weeks 52 and 78 | 
| Non-vertebral fragility fracture incidence | Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis. | Weeks 52 and 78 | 
| Percentage change from baseline in serum procollagen type 1 N terminal propeptide (P1NP) | Additional comparative pharmacodynamic data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis. | Baseline, Weeks 4, 26, 52 and 78 | 
| Percentage change from baseline in serum type I collagen C-telopeptide (sCTX) | Additional comparative pharmacodynamic data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis. | Baseline, Weeks 4, 26, 52 and 78 | 
| Number of participants with adverse events (AEs) | The safety and tolerability of RGB-14-P with US-licensed Prolia® will be compared in female participants with postmenopausal osteoporosis will be compared. | From Screening (Weeks -5 to 0) until Week 78 | 
| Number of participants with anti-drug antibodies (ADAs) and neutralizing antibodies | The immunogenicity of RGB -14- P with US-licensed Prolia® in female participants with postmenopausal osteoporosis will be compared. | Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78 | 
| Titre of ADAs against RGB-14-P | The immunogenicity of RGB -14- P with US-licensed Prolia® in female participants with postmenopausal osteoporosis will be compared. | Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biosimilars, Prolia®