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.

Study Overview

• Status: Completed
• Conditions: Postmenopausal Osteoporosis
• Intervention / Treatment: Drug: RGB-14-P; Drug: Prolia®

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 473
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5803
    • Medical Center Medconsult Pleven
  • Plovdiv, Bulgaria, 4001
    • UMHAT Kaspela
  • Plovdiv, Bulgaria, 4002
    • DKC "Sveti Georgi"
  • Plovdiv, Bulgaria, 4002
    • UMHAT Kaspela (Endocrinology/metabolic disease)
  • Plovdiv, Bulgaria, 4002
    • UMHAT Pulmed - Reumathology
  • Plovdiv, Bulgaria
    • UMHAT Plovdiv
  • Ruse, Bulgaria
    • Medical Center - Teodora EOOD
  • Sofia, Bulgaria, 1407
    • Medical Center Excelsior
  • Sofia, Bulgaria, 1505
    • "DCC XVII-Sofia" EOOD
  • Sofia-Grad
    • Sofia, Sofia-Grad, Bulgaria, 1510
      • Medical Center Hera EOOD - Rheumatology Office
• Czechia
  • Hradec Králové, Czechia, 500 05
    • FN Hradec Králové
  • Klatovy, Czechia, 339 01
    • Klatovska nemocnice, a.s.
  • Plzen, Czechia
    • Fakultni nemocnice Plzen
  • Praha 11, Czechia, 148 00
    • Affidea Praha s.r.o.
  • Praha 2, Czechia, 128 50
    • Revmatologicky Ustav
  • Praha 5, Czechia, 305 99
    • Fakultni nemocnice v Motole
  • Ostrava-město
    • Ostrava, Ostrava-město, Czechia, 702 00
      • Apavar Lekarna
• Hungary
  • Budapest, Hungary, 1036
    • Qualiclinic Kft.
  • Budapest, Hungary
    • Semmelweis Egyetem
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flor Ferenc Korhaz
  • Szentes, Hungary, 6600
    • Csongrad Megyei Dr Bugyi Istvan Korhaz
  • Borsod-Abaúj-Zemplén
    • Miskolc, Borsod-Abaúj-Zemplén, Hungary, 3529
      • BAZM KKH EOK Szt Ferenc Tagkh
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Debreceni Egyetem Klinikai Kozpont
• Italy
  • Pavia, Italy, 27100
    • Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
  • Perugia, Italy, 06125
    • Azienda Ospedaliera di Perugia - Ospedale Santa Maria della
  • Veneto, Italy, 37126
    • Azienda Ospedaliero Universitaria Integrata Verona
• Poland
  • Bydgoszcz, Poland, 85-065
    • Nasz Lekarz Osrodek Badan Klinicznych
  • Gdynia, Poland, 81-338
    • Centrum Medyczne Pratia Gdynia
  • Katowice, Poland, 40-081
    • Centrum Medyczne Pratia Katowice
  • Kraków, Poland, 30-363
    • Centrum Medyczne Plejady
  • Oswiecim, Poland, 32-600
    • Oswiecimskie Centrum Badan Klinicznych
  • Sochaczew, Poland, 96-500
    • RCMed Oddzial Sochaczew
  • Sochaczew, Poland, 96-500
    • RCMed
  • Warszawa, Poland, 00-874
    • Medycyna Kliniczna
  • Warszawa, Poland, 00-892
    • RCMed Oddział Warszawa
  • Warszawa, Poland, 02-691
    • Centrum Medyczne Reuma Park
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-607
      • Zespol Poradni Specjalistycznych REUMED, Filia nr 1 Wallenroda
    • Świdnik, Lubelskie, Poland, 21-040
      • Lubelskie Centrum Diagnostyczne
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-559
      • Barbara Rewerska Diamond Clin.
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-507
      • Centralny Szpital Kliniczny MSWiA w Warszawie
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-082
      • Nasz Lekarz Osrodek Badan Klinicznych
    • Bialystok, Podlaskie, Poland, 15-879
      • ClinicMed Daniluk, Nowak Sp. J
    • Białystok, Podlaskie, Poland, 15-082
      • Komisja Bioetyczna przy OIL w Bialymstoku
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruna
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain, 28009
    • Centro Medico Instituto Palacios
  • Santiago De Compostela, Spain, 15703
    • Clínica Gaias Santiago
  • A Coruña
    • Santiago De Compostela, A Coruña, Spain, 15705
      • H. Ntra. Sra. de la Esperanza
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli de Sabadell - Servicio de reumatologia
• Ukraine
  • Kyïv, Ukraine, 03049
    • Kyivska klinichna likarnia na zaliznychnomu transporti #2 filii "Tsentr okhorony zdoroviya" AT "Ukrayinska Zaliznytsia"
  • Kyïv, Ukraine, 04210
    • Med tsentr TOV "Tsentr simeinoi medytsyny plius"
  • Kyïv
    • Kyiv, Kyïv, Ukraine, 0 3037
      • Medychnyi tsentr tovarystva z obmezhenoyu vidpovidalnistyu "Medbud-Klinik"
    • Kyiv, Kyïv, Ukraine, 04114
      • Derzhavna ustanova "Instytut herontolohii imeni D.F. Chebotarova Natsionalnoi akademii medychnykh nauk Ukrainy
  • Vinnyts'ka Oblast'
    • Vinnytsia, Vinnyts'ka Oblast', Ukraine, 21018
      • Vinnytska oblasna klinichna likarnia im. M.I. Pyrohova
    • Vinnytsia, Vinnyts'ka Oblast', Ukraine, 21029
      • Naukovo-doslidnyi instytut reabilitatsii osib z invalidnistiu (navchalno-naukovo-likuvalnyi kompleks) Vinnytskoho natsionalnoho medychnoho universytetu im. M.I. Pyrohova
• United States
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Clinical Research
    • Miami Lakes, Florida, United States, 33016
      • Global Health Research center
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research - Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (BMD)	Percentage change from baseline in lumbar bone BMD was assessed. BMD at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). This outcome measure was assessed for main period.	Week 52
Area Under the Effective Curve (AUEC) After the First Dose Until Day 183 of %CfB in Serum Type I Collagen C-telopeptide (sCTX)	The AUEC of %CfB in sCTX of RGB-14-P was assessed as part of pharmacodynamics parameter with US-licensed Prolia® in female participants was demonstrated with postmenopausal osteoporosis. This outcome measure was assessed for main period only.	Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
%CfB in Total Hip BMD	%CfB in total hip BMD was assessed.	Weeks 26, 52 and 78
%CfB in Lumbar Spine BMD	%CfB in lumbar spine BMD was assessed.	Weeks 26 and 78
%CfB in Femoral Neck BMD	%CfB in femoral neck BMD was assessed by DXA.	Weeks 26, 52 and 78
Number of Participants With Vertebral Fragility Fracture	Number of participants with vertebral fragility fracture was assessed. Information on vertebral fractures was centrally collected through the evaluation of lateral thoraco-lumbar spine X-ray.	Weeks 52 and 78
Number of Participants With Non-vertebral Fragility Fracture	Number of participants with non-vertebral fragility fracture was assessed. Information on non-vertebral fractures was centrally collected through the evaluation of lateral thoraco-lumbar spine X-ray.	Weeks 52 and 78
%CfB in Serum Procollagen Type 1 N Terminal Propeptide (P1NP)	%CfB in serum P1NP was assessed as part of pharmacodynamics parameter with US-licensed Prolia® in female participants with postmenopausal osteoporosis.	Weeks 4, 26, 52 and 78
%CfB in Serum Type I Collagen C-telopeptide (sCTX)	%CfB in sCTX was assessed as part of pharmacodynamics parameter with US-licensed Prolia® was assessed in female participants with postmenopausal osteoporosis.	Weeks 4, 26, 52 and 78
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	The safety and tolerability of RGB-14-P with US-licensed Prolia® in female participants with postmenopausal osteoporosis was assessed.	Main Period: From screening (Weeks -5 to 0) to Week 52; Transition Period: From Week 52 to Week 78
Number of Participants With Anti-drug Antibodies (ADAs)	Number of participants with positive ADAs was assessed.	Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
Number of Participants With Neutralizing Antibodies	Number of participants with positive neutralizing antibodies was assessed.	Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
Titre of ADAs	The immunogenicity of RGB -14- P with US-licensed Prolia® in female participants with postmenopausal osteoporosis was assessed.	Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78

Collaborators and Investigators

• Sponsor: Gedeon Richter Plc.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): November 15, 2023

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 21, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Biosimilars; Prolia®
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: RGB 14 101; 2020 006017 38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No