Clinical trial NCT05087030: Comparative Efficacy and Safety Study of RGB-14-P and Prolia® in Women With Postmenopausal Osteoporosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postmenopausal Osteoporosis
Keywords: Biosimilars
Prolia®
Lead sponsor: Gedeon Richter Plc.
Sponsor class: INDUSTRY
First posted: 2021-10-21
Enrollment: 473
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (BMD)
timeFrame: Week 52
measure: Area Under the Effective Curve (AUEC) After the First Dose Until Day 183 of %CfB in Serum Type I Collagen C-telopeptide (sCTX)
timeFrame: Week 26
Secondary outcomes:
measure: %CfB in Total Hip BMD
timeFrame: Weeks 26, 52 and 78
measure: %CfB in Lumbar Spine BMD
timeFrame: Weeks 26 and 78
measure: %CfB in Femoral Neck BMD
timeFrame: Weeks 26, 52 and 78
measure: Number of Participants With Vertebral Fragility Fracture
timeFrame: Weeks 52 and 78
measure: Number of Participants With Non-vertebral Fragility Fracture
timeFrame: Weeks 52 and 78
measure: %CfB in Serum Procollagen Type 1 N Terminal Propeptide (P1NP)
timeFrame: Weeks 4, 26, 52 and 78
measure: %CfB in Serum Type I Collagen C-telopeptide (sCTX)
timeFrame: Weeks 4, 26, 52 and 78
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Main Period: From screening (Weeks -5 to 0) to Week 52; Transition Period: From Week 52 to Week 78
measure: Number of Participants With Anti-drug Antibodies (ADAs)
timeFrame: Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
measure: Number of Participants With Neutralizing Antibodies
timeFrame: Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
measure: Titre of ADAs
timeFrame: Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78
Other outcomes:
Locations:
city: Miami Lakes
country: United States
facility: Global Health Research Center
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta, LLC
state: Georgia
city: Las Vegas
country: United States
facility: Excel Clinical Research - Internal Medicine
state: Nevada
city: Sofia
country: Bulgaria
facility: Medical Center Hera EOOD - Rheumatology Office
state: Sofia-Grad
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven
city: Plovdiv
country: Bulgaria
facility: UMHAT Kaspela
city: Plovdiv
country: Bulgaria
facility: DKC "Sveti Georgi"
city: Plovdiv
country: Bulgaria
facility: UMHAT Kaspela (Endocrinology/metabolic disease)
city: Plovdiv
country: Bulgaria
facility: UMHAT Pulmed - Reumathology
city: Plovdiv
country: Bulgaria
facility: UMHAT Plovdiv
city: Ruse
country: Bulgaria
facility: Medical Center - Teodora EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior
city: Sofia
country: Bulgaria
facility: "DCC XVII-Sofia" EOOD
city: Ostrava
country: Czechia
facility: APAVAR Lekarna
state: Ostrava-město
city: Hradec Králové
country: Czechia
facility: FN Hradec Kralove
city: Klatovy
country: Czechia
facility: Klatovska nemocnice, a.s.
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen
city: Praha 11
country: Czechia
facility: Affidea Praha s.r.o.
city: Praha 2
country: Czechia
facility: Revmatologicky ustav
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Miskolc
country: Hungary
facility: BAZM KKH EOK Szt Ferenc Tagkh
state: Borsod-Abaúj-Zemplén
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
state: Hajdú-Bihar
city: Budapest
country: Hungary
facility: Qualiclinic Kft.
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Szentes
country: Hungary
facility: Csongrad Megyei Dr Bugyi Istvan Korhaz
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo, Università degli studi di Pavi
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia - Ospedale Santa Maria della
city: Veneto
country: Italy
facility: Azienda Ospedaliero Universitaria Integrata Verona
city: Lublin
country: Poland
facility: Zespol Poradni Specjalistycznych REUMED, Filia nr 1 Wallenroda
state: Lubelskie
city: Świdnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne
state: Lubelskie
city: Krakow
country: Poland
facility: Barbara Rewerska Diamond Clin.
state: Malopolskie
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
state: Mazowieckie
city: Bialystok
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych
state: Podlaskie
city: Bialystok
country: Poland
facility: ClinicMed Daniluk, Nowak Sp. J
state: Podlaskie
city: Białystok
country: Poland
facility: Komisja Bioetyczna przy OIL w Bialymstoku
state: Podlaskie
city: Bydgoszcz
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Oswiecim
country: Poland
facility: Oswiecimskie Centrum Badan Klinicznych
city: Sochaczew
country: Poland
facility: RCMed Oddzial Sochaczew
city: Sochaczew
country: Poland
facility: RCMed
city: Warszawa
country: Poland
facility: Medycyna Kliniczna
city: Warszawa
country: Poland
facility: RCMed Oddział Warszawa
city: Warszawa
country: Poland
facility: Centrum Medyczne Reuma Park
city: Santiago De Compostela
country: Spain
facility: H. Ntra. Sra. de la Esperanza
state: A Coruña
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli de Sabadell - Servicio de reumatologia
state: Barcelona
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Centro Medico Instituto Palacios
city: Santiago De Compostela
country: Spain
facility: Clinica Gaias Santiago
city: Kyiv
country: Ukraine
facility: Medychnyi tsentr tovarystva z obmezhenoyu vidpovidalnistyu "Medbud-Klinik"
state: Kyïv
city: Kyiv
country: Ukraine
facility: Derzhavna ustanova "Instytut herontolohii imeni D.F. Chebotarova Natsionalnoi akademii medychnykh nauk Ukrainy
state: Kyïv
city: Vinnytsia
country: Ukraine
facility: Vinnytska oblasna klinichna likarnia im. M.I. Pyrohova
state: Vinnyts'ka Oblast'
city: Vinnytsia
country: Ukraine
facility: Naukovo-doslidnyi instytut reabilitatsii osib z invalidnistiu (navchalno-naukovo-likuvalnyi kompleks) Vinnytskoho natsionalnoho medychnoho universytetu im. M.I. Pyrohova
state: Vinnyts'ka Oblast'
city: Kyïv
country: Ukraine
facility: Kyivska klinichna likarnia na zaliznychnomu transporti #2 filii "Tsentr okhorony zdoroviya" AT "Ukrayinska Zaliznytsia"
city: Kyïv
country: Ukraine
facility: Med tsentr TOV "Tsentr simeinoi medytsyny plius"
Study officials:
References: