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

Postmenopausal Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05087030
• Other study ID #: RGB 14 101
• Secondary ID: 2020 006017 38
• Status: Completed
• Phase: Phase 3
• Start date: September 21, 2021
• Est. completion date: November 15, 2023

Study information

• Verified date: December 2023
• Source: Gedeon Richter Plc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 473
• Est. completion date: November 15, 2023
• Est. primary completion date: October 2, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Postmenopausal Osteoporosis

Intervention

Drug:
• RGB-14-P
Participants will receive RGB-14-P into the thigh, abdomen, or upper arm as per the arm assigned.
• Prolia®
Participants will receive Prolia® into the thigh, abdomen, or upper arm as per the arm assigned.

Locations

Country	Name	City	State
Bulgaria	Medical Center Medconsult Pleven	Pleven
Bulgaria	DKC "Sveti Georgi"	Plovdiv
Bulgaria	UMHAT Kaspela	Plovdiv
Bulgaria	UMHAT Kaspela (Endocrinology/metabolic disease)	Plovdiv
Bulgaria	UMHAT Plovdiv	Plovdiv
Bulgaria	UMHAT Pulmed - Reumathology	Plovdiv
Bulgaria	Medical Center - Teodora EOOD	Ruse
Bulgaria	"DCC XVII-Sofia" EOOD	Sofia
Bulgaria	Medical Center Excelsior	Sofia
Bulgaria	Medical Center Hera EOOD - Rheumatology Office	Sofia	Sofia-Grad
Czechia	FN Hradec Kralove	Hradec Králové
Czechia	Klatovska nemocnice, a.s.	Klatovy
Czechia	APAVAR Lekarna	Ostrava	Ostrava-mesto
Czechia	Fakultni nemocnice Plzen	Plzen
Czechia	Affidea Praha s.r.o.	Praha 11
Czechia	Revmatologicky ustav	Praha 2
Czechia	Fakultni nemocnice v Motole	Praha 5
Hungary	Qualiclinic Kft.	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen	Hajdú-Bihar
Hungary	Pest Megyei Flor Ferenc Korhaz	Kistarcsa
Hungary	BAZM KKH EOK Szt Ferenc Tagkh	Miskolc	Borsod-Abaúj-Zemplén
Hungary	Csongrad Megyei Dr Bugyi Istvan Korhaz	Szentes
Italy	IRCCS Policlinico San Matteo, Università degli studi di Pavi	Pavia
Italy	Azienda Ospedaliera di Perugia - Ospedale Santa Maria della	Perugia
Italy	Azienda Ospedaliero Universitaria Integrata Verona	Veneto
Poland	ClinicMed Daniluk, Nowak Sp. J	Bialystok	Podlaskie
Poland	Komisja Bioetyczna przy OIL w Bialymstoku	Bialystok	Podlaskie
Poland	Nasz Lekarz Osrodek Badan Klinicznych	Bialystok	Podlaskie
Poland	Nasz Lekarz Osrodek Badan Klinicznych	Bydgoszcz
Poland	Centrum Medyczne Pratia Gdynia	Gdynia
Poland	Centrum Medyczne Pratia Katowice	Katowice
Poland	Barbara Rewerska Diamond Clin.	Krakow	Malopolskie
Poland	Centrum Medyczne Plejady	Kraków
Poland	Zespol Poradni Specjalistycznych REUMED, Filia nr 1 Wallenroda	Lublin	Lubelskie
Poland	Oswiecimskie Centrum Badan Klinicznych	Oswiecim
Poland	RCMed	Sochaczew
Poland	RCMed Oddzial Sochaczew	Sochaczew
Poland	Lubelskie Centrum Diagnostyczne	Swidnik	Lubelskie
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie	Warszawa	Mazowieckie
Poland	Centrum Medyczne Reuma Park	Warszawa
Poland	Medycyna Kliniczna	Warszawa
Poland	RCMed Oddzial Warszawa	Warszawa
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Centro Medico Instituto Palacios	Madrid
Spain	Corporacio Sanitaria Parc Tauli de Sabadell - Servicio de reumatologia	Sabadell	Barcelona
Spain	Clinica Gaias Santiago	Santiago De Compostela
Spain	H. Ntra. Sra. de la Esperanza	Santiago De Compostela	A Coruña
Ukraine	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	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	Naukovo-doslidnyi instytut reabilitatsii osib z invalidnistiu (navchalno-naukovo-likuvalnyi kompleks) Vinnytskoho natsionalnoho medychnoho universytetu im. M.I. Pyrohova	Vinnytsia	Vinnyts'ka Oblast'
Ukraine	Vinnytska oblasna klinichna likarnia im. M.I. Pyrohova	Vinnytsia	Vinnyts'ka Oblast'
United States	iResearch Atlanta, LLC	Decatur	Georgia
United States	Excel Clinical Research - Internal Medicine	Las Vegas	Nevada
United States	Miami Clinical Research	Miami	Florida
United States	Global Health Research Center	Miami Lakes	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gedeon Richter Plc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Hungary,  Italy,  Poland,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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