Comparative Efficacy and Safety Study of RGB-14-P and Prolia® in Women With Postmenopausal Osteoporosis
- Registration Number
- NCT05087030
- Lead Sponsor
- Gedeon Richter Plc.
- Brief 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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 473
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RGB-14-P (Main period) RGB-14-P Randomized participants will receive subcutaneous (SC) injection of RGB-14-P, on Day 1 of Treatment periods 1 and 2. RGB-14-P (Transition period) RGB-14-P Re-randomized participants will receive SC injection of RGB-14-P, on Day 1 of Treatment period 3. Prolia® (Transition period) Prolia® Re-randomized participants will receive SC injection of Prolia®, on Day 1 of Treatment period 3. RGB-14-P (Continued till transition period) RGB-14-P Randomized participants will continue to receive SC injection of RGB-14-P from the main period till Day 1 of Treatment period 3. Prolia® (Main period) Prolia® Randomized participants will receive SC injection of Prolia®, on Day 1 of Treatment periods 1 and 2.
- Primary Outcome Measures
Name Time Method Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (BMD) Week 52 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.
Area Under the Effective Curve (AUEC) After the First Dose Until Day 183 of %CfB in Serum Type I Collagen C-telopeptide (sCTX) Week 26 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.
- Secondary Outcome Measures
Name Time Method %CfB in Total Hip BMD Weeks 26, 52 and 78 %CfB in total hip BMD was assessed.
%CfB in Lumbar Spine BMD Weeks 26 and 78 %CfB in lumbar spine BMD was assessed.
%CfB in Femoral Neck BMD Weeks 26, 52 and 78 %CfB in femoral neck BMD was assessed by DXA.
Number of Participants With Vertebral Fragility Fracture Weeks 52 and 78 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.
Number of Participants With Non-vertebral Fragility Fracture Weeks 52 and 78 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.
%CfB in Serum Procollagen Type 1 N Terminal Propeptide (P1NP) Weeks 4, 26, 52 and 78 %CfB in serum P1NP was assessed as part of pharmacodynamics parameter with US-licensed Prolia® in female participants with postmenopausal osteoporosis.
%CfB in Serum Type I Collagen C-telopeptide (sCTX) Weeks 4, 26, 52 and 78 %CfB in sCTX was assessed as part of pharmacodynamics parameter with US-licensed Prolia® was assessed in female participants with postmenopausal osteoporosis.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Main Period: From screening (Weeks -5 to 0) to Week 52; Transition Period: From Week 52 to Week 78 The safety and tolerability of RGB-14-P with US-licensed Prolia® in female participants with postmenopausal osteoporosis was assessed.
Number of Participants With Anti-drug Antibodies (ADAs) Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78 Number of participants with positive ADAs was assessed.
Number of Participants With Neutralizing Antibodies Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78 Number of participants with positive neutralizing antibodies was assessed.
Titre of ADAs Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78 The immunogenicity of RGB -14- P with US-licensed Prolia® in female participants with postmenopausal osteoporosis was assessed.
Trial Locations
- Locations (58)
Zespol Poradni Specjalistycznych REUMED, Filia nr 1 Wallenroda
🇵🇱Lublin, Lubelskie, Poland
RCMed Oddział Warszawa
🇵🇱Warszawa, Poland
Global Health Research Center
🇺🇸Miami Lakes, Florida, United States
Miami Clinical Research
🇺🇸Miami, Florida, United States
iResearch Atlanta, LLC
🇺🇸Decatur, Georgia, United States
Medical Center Medconsult Pleven
🇧🇬Pleven, Bulgaria
DKC "Sveti Georgi"
🇧🇬Plovdiv, Bulgaria
"DCC XVII-Sofia" EOOD
🇧🇬Sofia, Bulgaria
Affidea Praha s.r.o.
🇨🇿Praha 11, Czechia
Revmatologicky ustav
🇨🇿Praha 2, Czechia
Azienda Ospedaliero Universitaria Integrata Verona
🇮🇹Veneto, Italy
Centrum Medyczne Pratia Katowice
🇵🇱Katowice, Poland
RCMed
🇵🇱Sochaczew, Poland
Nasz Lekarz Osrodek Badan Klinicznych
🇵🇱Bydgoszcz, Poland
Derzhavna ustanova "Instytut herontolohii imeni D.F. Chebotarova Natsionalnoi akademii medychnykh nauk Ukrainy
🇺🇦Kyiv, Kyïv, Ukraine
Medychnyi tsentr tovarystva z obmezhenoyu vidpovidalnistyu "Medbud-Klinik"
🇺🇦Kyiv, Kyïv, Ukraine
Excel Clinical Research - Internal Medicine
🇺🇸Las Vegas, Nevada, United States
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Medical Center Hera EOOD - Rheumatology Office
🇧🇬Sofia, Sofia-Grad, Bulgaria
UMHAT Kaspela
🇧🇬Plovdiv, Bulgaria
UMHAT Pulmed - Reumathology
🇧🇬Plovdiv, Bulgaria
UMHAT Kaspela (Endocrinology/metabolic disease)
🇧🇬Plovdiv, Bulgaria
Medical Center - Teodora EOOD
🇧🇬Ruse, Bulgaria
UMHAT Plovdiv
🇧🇬Plovdiv, Bulgaria
Medical Center Excelsior
🇧🇬Sofia, Bulgaria
FN Hradec Kralove
🇨🇿Hradec Králové, Czechia
APAVAR Lekarna
🇨🇿Ostrava, Ostrava-město, Czechia
Klatovska nemocnice, a.s.
🇨🇿Klatovy, Czechia
Fakultni nemocnice Plzen
🇨🇿Plzen, Czechia
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hajdú-Bihar, Hungary
Qualiclinic Kft.
🇭🇺Budapest, Hungary
Csongrad Megyei Dr Bugyi Istvan Korhaz
🇭🇺Szentes, Hungary
Pest Megyei Flor Ferenc Korhaz
🇭🇺Kistarcsa, Hungary
Azienda Ospedaliera di Perugia - Ospedale Santa Maria della
🇮🇹Perugia, Italy
IRCCS Policlinico San Matteo, Università degli studi di Pavi
🇮🇹Pavia, Italy
Lubelskie Centrum Diagnostyczne
🇵🇱Świdnik, Lubelskie, Poland
Barbara Rewerska Diamond Clin.
🇵🇱Krakow, Malopolskie, Poland
Centralny Szpital Kliniczny MSWiA w Warszawie
🇵🇱Warszawa, Mazowieckie, Poland
ClinicMed Daniluk, Nowak Sp. J
🇵🇱Bialystok, Podlaskie, Poland
Komisja Bioetyczna przy OIL w Bialymstoku
🇵🇱Białystok, Podlaskie, Poland
Centrum Medyczne Pratia Gdynia
🇵🇱Gdynia, Poland
RCMed Oddzial Sochaczew
🇵🇱Sochaczew, Poland
Centro Medico Instituto Palacios
🇪🇸Madrid, Spain
Corporacio Sanitaria Parc Tauli de Sabadell - Servicio de reumatologia
🇪🇸Sabadell, Barcelona, Spain
H. Ntra. Sra. de la Esperanza
🇪🇸Santiago De Compostela, A Coruña, Spain
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Clinica Gaias Santiago
🇪🇸Santiago De Compostela, Spain
Hospital de La Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Vinnytska oblasna klinichna likarnia im. M.I. Pyrohova
🇺🇦Vinnytsia, Vinnyts'ka Oblast', Ukraine
Oswiecimskie Centrum Badan Klinicznych
🇵🇱Oswiecim, Poland
Medycyna Kliniczna
🇵🇱Warszawa, Poland
Centrum Medyczne Plejady
🇵🇱Kraków, Poland
Centrum Medyczne Reuma Park
🇵🇱Warszawa, Poland
BAZM KKH EOK Szt Ferenc Tagkh
🇭🇺Miskolc, Borsod-Abaúj-Zemplén, Hungary
Naukovo-doslidnyi instytut reabilitatsii osib z invalidnistiu (navchalno-naukovo-likuvalnyi kompleks) Vinnytskoho natsionalnoho medychnoho universytetu im. M.I. Pyrohova
🇺🇦Vinnytsia, Vinnyts'ka Oblast', Ukraine
Kyivska klinichna likarnia na zaliznychnomu transporti #2 filii "Tsentr okhorony zdoroviya" AT "Ukrayinska Zaliznytsia"
🇺🇦Kyïv, Ukraine
Med tsentr TOV "Tsentr simeinoi medytsyny plius"
🇺🇦Kyïv, Ukraine