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

• Sponsor: Gedeon Richter Plc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05087030
• Collaborator: (none)
• Enrollment: 434
• Locations: 58
• Arms: 5
• Anticipated Duration (Months): 25.3
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Osteoporosis	Drug: RGB-14-P; Drug: Prolia®	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 434 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Masking Description: A double-blind design will be used during the main and transition periods.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 21, 2021
• Anticipated Primary Completion Date: Jun 30, 2023
• Anticipated Study Completion Date: Oct 30, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Percentage change from baseline in lumbar spine bone mineral density (BMD) [Baseline, Week 52]

   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.

2. Area under the effective curve after the first dose until Day 183 of percentage change from baseline in serum type I collagen C-telopeptide up to month 6 (AUEC of %CfB in sCTX00-m6) until Week 26 [Baseline, until Week 26 (Predose)]

   Similar pharmacodynamics (AUEC of %CfB in sCTX) of RGB-14-P with US-licensed Prolia® in female participants will be demonstrated with postmenopausal osteoporosis.

Secondary Outcome Measures

1. Percentage change from baseline in total hip BMD [Baseline, Weeks 26, 52 and 78]

   Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis.

2. Percentage change from baseline in lumbar spine BMD [Baseline, Weeks 26 and 78]

   Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis.

3. Percentage change from baseline in femoral neck BMD [Baseline, Weeks 26, 52 and 78]

   Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis.

4. Vertebral fragility fracture incidence [Weeks 52 and 78]

   Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis.

5. Non-vertebral fragility fracture incidence [Weeks 52 and 78]

   Additional comparative efficacy data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis.

6. Percentage change from baseline in serum procollagen type 1 N terminal propeptide (P1NP) [Baseline, Weeks 4, 26, 52 and 78]

   Additional comparative pharmacodynamic data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis.

7. Percentage change from baseline in serum type I collagen C-telopeptide (sCTX) [Baseline, Weeks 4, 26, 52 and 78]

   Additional comparative pharmacodynamic data of RGB-14-P with US-licensed Prolia® will be evaluated in female participants with postmenopausal osteoporosis.

8. Number of participants with adverse events (AEs) [From Screening (Weeks -5 to 0) until Week 78]

   The safety and tolerability of RGB-14-P with US-licensed Prolia® will be compared in female participants with postmenopausal osteoporosis will be compared.

9. Number of participants with anti-drug antibodies (ADAs) and neutralizing antibodies [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 will be compared.

10. Titre of ADAs against RGB-14-P [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 will be compared.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 90 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Gedeon Richter Plc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gedeon Richter Plc.
• ClinicalTrials.gov Identifier: NCT05087030
• Other Study ID Numbers: RGB 14 101; 2020 006017 38
• First Posted: Oct 21, 2021
• Last Update Posted: Mar 9, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gedeon Richter Plc.: Biosimilars; Prolia®
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Denosumab

Study Results

No Results Posted as of Mar 9, 2022