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Comparative Efficacy, Safety, PK, and Immunogenicity Study of LY06006 and EU-Prolia in Postmenopausal Women With Osteoporosis

Primary Purpose

Osteoporosis, Postmenopausal

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Denosumab
Sponsored by
Luye Pharma Group Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Osteoporosis, Postmenopausal focused on measuring Comparative efficacy;safety;pharmacokinetic; immunogenicity ; biosimilar

Eligibility Criteria

60 Years - 90 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Age Participant is ≥ 60 to ≤ 90 years of age inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics Participant is an ambulatory postmenopausal woman (defined as lack of menstrual period for at least 12 months prior to Screening Visit, for which there is no other obvious pathological or physiological cause). Serum FSH test can be done at the Screening Visit in case of uncertainty. Female participants who underwent bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior to the Screening Period are eligible to participate. Participant is diagnosed with osteoporosis, with absolute BMD consistent with a T-score of ≤ -2.5 and ≥ -4.0 at the lumbar spine (L1-L4 region) as measured by DXA at the Screening Visit. Participant has at least two lumbar vertebrae in L1-L4 region and one hip evaluable by DXA for BMD measurement at the Screening Visit. Weight 5. Participant has body weight ≥ 50 kg and ≤ 90 kg at Screening. Informed Consent 6. Participant is able to read and understand, and willing to provide signed informed consent as described in Appendix 1, Section 10.1.3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. - Exclusion Criteria: Medical Conditions Participant has a history and/or presence of any severe or more than two moderate vertebral fractures as determined by central reading of lateral spine X-ray at Screening Visit. Participant has a history and/or presence of hip fracture. Participant has a history and/or presence of atypical femur fracture. Participant presents with any active healing fracture, per assessment of the Investigator. Participant has a history of bilateral hip replacement (unilateral is allowed if the other hip is evaluable by DXA). Participant has history and/or presence of osteonecrosis of the external auditory canal. Evidence of any of the following conditions which may affect BMD or interfere with the interpretation of the findings: Participant has a history of bone disease e.g., osteomalacia, osteopetrosis, Paget's disease, or osteogenesis imperfecta. Participant has a history of metabolic or other endocrinologic diseases such as Cushing's disease, hyperprolactinemia, hypopituitarism, acromegaly, malabsorption syndrome (or any gastrointestinal disorders associated with malabsorption, e.g., Crohn's disease and chronic pancreatitis). Participant has a history of chronic inflammatory diseases, obvious sclerosis, osteophytosis, severe scoliosis, or other degenerative changes due to other co-morbidities. Participant has a history or current hyperparathyroidism or hypoparathyroidism. Note: Mild non-clinically significant secondary hyperparathyroidism may be acceptable upon discussion with the Medical Monitor. Participant has current uncontrolled hyperthyroidism or hypothyroidism. Note: Participants with hypothyroidism who are on stable thyroid hormone replacement therapy may be allowed per the following criteria: If TSH level is within normal range, the participant is eligible. If TSH level is elevated (> 5.5 μIU/mL and ≤ 10.0 μIU/mL) and serum free T4 is within normal range, the participant is eligible. If TSH is below the lower level of normal, the participant should be excluded. Participant has other disease conditions where there is bone/joint involvement (e.g., rheumatoid arthritis, ankylosing spondylitis, gout, multiple myeloma, achondroplasia, bone metastases, renal osteodystrophy, osteomyelitis). Participant has hypocalcemia (defined as albumin adjusted serum calcium level < 2.0 mmol/L [8.0 mg/dL] Grade 2 per Common Terminology Criteria for Adverse Events version 5.0) or hypercalcemia (defined as albumin adjusted serum calcium levels > 2.62 mmol/L [10.50 mg/dL]). Participant has vitamin D deficiency (defined as 25-hydroxy vitamin D level < 20 ng/mL [< 50 nmol/L]). Note: Oral replenishment of vitamin D is permitted at the discretion of the Investigator and in accordance with local standard of care during the Screening Period. Participants can be enrolled if a repeat test (post supplementation) prior to enrollment shows corrected 25-hydroxy vitamin D level ≥ 20 ng/mL (≥ 50 nmol/L). Participant has any malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years. Participant has known history of liver cirrhosis. Participant has known history of hepatitis B, hepatitis C, or HIV infection, or an active infection including, but not limited to SARS-CoV-2, tests positive for hepatitis B (positive HBsAg, positive anti-HBc with negative anti-HBs), hepatitis C (hepatitis C antibody), or HIV antibody during the Screening Period. Participant has oral or dental conditions: Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw. Active dental or jaw condition which requires oral surgery. Invasive dental procedure planned during the study or within the past 6 months (e.g., tooth extraction, dental implants, oral surgery). Non-healed dental or oral surgery. Active periodontal disease. Poor oral hygiene. Participant has a history of major surgery within 8 weeks prior to the Screening Period or planned, anticipated major surgery during the study. Participant has a history and/or presence of significant cardiac disease or ECG abnormalities indicating significant risk for participating in the study as judged by the Investigator. Prior/Concomitant Therapy Participant shows contraindications to denosumab therapy (e.g., hypocalcemia), or calcium or vitamin D supplementation before starting study intervention administration. Participant requires ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements). Use of any of the below medications that can affect BMD: l. Denosumab used at any time prior to Screening Visit. Oral bisphosphonates at any dose for osteoporosis treatment: Used for > 3 years cumulatively at Screening Visit. At any dose used within 1 year prior to Screening Visit (if ≤ 3 years of use cumulatively). Intravenous bisphosphonate at any dose within 5 years prior to Screening Visit. PTH or PTH analogues at any dose within 2 years prior to Screening Visit. Systemic HRT (oral or transdermal estrogen), SERMs, tibolone, aromatase inhibitors, or androgens at any dose within 1 year prior to Screening Visit. Note: Exceptionally, non-systemic vaginal estrogen treatment is permitted. Calcitonin, or its derivatives, and calcimimetics (such as cinacalcet or etelcalcetide) at any dose within 12 months prior to Screening Visit. Calcitriol, alfacalcidol, or eldecalcitol within 3 months of the Screening Visit. Fluoride or strontium at any dose at any time prior to Screening Visit. Romosozumab or cathepsin K inhibitors received at any time prior to Screening Visit. Systemic glucocorticoids (≥ 5 mg prednisone or equivalent per day for more than 10 days or cumulative ≥ 50 mg) within 3 months prior to Screening Visit. Other bone active drugs including anticonvulsants (except benzodiazepines, gabapentin, and pregabalin), heparin (including low molecular weight heparins), vitamin K (supplementation or therapeutic dose), vitamin K antagonists (e.g., warfarin, acenocumarol), emtricitabine, tenofovir, adefovir, systemic ketoconazole, adrenocorticotropic hormone, lithium, protease inhibitors, gonadotropin-releasing hormone agonist, aluminum, barbiturate, methotrexate, chemotherapeutic agents, cyclosporine, tacrolimus, or anabolic steroids at any dose within 3 months prior to Screening Visit. Prior/Concurrent Clinical Study Experience Participant is receiving or has received another investigational product within 1 month or 5 half-lives of the other investigational product, whichever is longer, before study intervention administration in this study. Diagnostic Assessments Participant has DXA measurements where: Height, weight, or girth measurements may preclude accurate DXA measurements in the Investigator's opinion. BMD absolute value is consistent with a T-score < -4.0 at the total hip or femoral neck. Participant has severe renal impairment (defined as participant in dialysis or with an eGFR < 30 mL/min per MDRD formula). Participant has inadequate hepatic function (ALT and/or AST ≥ 2 × ULN). Participant presents with clinically significant leukopenia, neutropenia, or anemia as judged by the Investigator. Other Exclusion Criteria Participant has a known intolerance to calcium or vitamin D supplements. Participant has a history of prescription drug abuse or any illicit drug use within 6 months prior to Screening Visit. Participant has a history of alcohol abuse (defined as consuming more than 3 drinks on any day or more than 7 drinks per week) according to medical history within 6 months prior to Screening Visit. Participant is a smoker or has used nicotine and nicotine-containing products within 12 months of Screening Visit. Participant has a known sensitivity to mammalian cell-derived drug products. Participant is immunosuppressed for any reason. Participant has any other conditions including clinically significant medical conditions/disorders/diseases, psychiatric status, or laboratory abnormalities that in the opinion of the Investigator might interfere with the participant's ability to participate in the study, would pose a risk to the participant's safety, or interfere with the study evaluation, procedure, or completion.

Sites / Locations

  • Shandong Boan Biotechnology Co., Ltd.Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LY06006

EU Prolia

Arm Description

to be administered 2 doses to the patients at the main treatment period and 1 dose at the transition period.

to be administered 2 doses to the patients at the main treatment period and 1 dose at the transition period.

Outcomes

Primary Outcome Measures

To demonstrate equivalent efficacy between LY06006 and EU-Prolia, in terms of BMD in female participants with postmenopausal osteoporosis;
%CfB in lumbar spine BMD at Month 12
EU Marketing Authorization only: To demonstrate similar PD between LY06006 and EU-Prolia, in terms of the bone resorption marker sCTX in female participants with postmenopausal osteoporosis
EU Marketing Authorization only: standardized AUEC0-6m (post first dose) of -%CfB in bone resorption marker sCTX over 6 months

Secondary Outcome Measures

To provide additional comparative efficacy data of LY06006 with EU-Prolia in female participants with postmenopausal osteoporosis
%CfB in lumbar spine BMD at Month 6 %CfB in total hip BMD at Months 6 and 12 %CfB in femoral neck BMD at Months 6 and 12

Full Information

First Posted
May 2, 2023
Last Updated
July 11, 2023
Sponsor
Luye Pharma Group Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05853354
Brief Title
Comparative Efficacy, Safety, PK, and Immunogenicity Study of LY06006 and EU-Prolia in Postmenopausal Women With Osteoporosis
Official Title
A Randomized, Double-blind, Parallel-group, Active-controlled Comparative Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Immunogenicity of LY06006 Compared With EU-Prolia in Postmenopausal Women With Osteoporosis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 5, 2023 (Actual)
Primary Completion Date
July 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Luye Pharma Group Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
this comparative clinical study is designed to demonstrate that LY06006 and EU-Prolia have no clinically meaningful differences in clinical efficacy, pharmacodynamic (PD), safety, PK, and immunogenicity in postmenopausal women with osteoporosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Postmenopausal
Keywords
Comparative efficacy;safety;pharmacokinetic; immunogenicity ; biosimilar

7. Study Design

Primary Purpose
Other
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This is a randomized, double-blind, parallel-group, active-controlled, comparative study (Main Period) with a Transition Period to compare the efficacy, PD, safety, PK and immunogenicity of LY06006 and EU-Prolia among female participants with postmenopausal osteoporosis.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Upon enrollment, each participant will receive a unique participant identification number.Participant numbers must not be re-used for any other participants. Prior to dosing in the Transition Period and to maintain the blind throughout the study, participants will be re-randomized and receive a second randomization number. Participants randomized to receive EU-Prolia in the Main Period will be re-randomized to receive either LY06006 or continue to receive EU-Prolia. Participants who received LY06006 in the Main Period will be re-randomized to continue to receive LY06006 in the Transition Period. All participant assignment during the Transition Period will be performed via the IRT system to maintain the blind of treatment assignment.
Allocation
Randomized
Enrollment
392 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LY06006
Arm Type
Experimental
Arm Description
to be administered 2 doses to the patients at the main treatment period and 1 dose at the transition period.
Arm Title
EU Prolia
Arm Type
Active Comparator
Arm Description
to be administered 2 doses to the patients at the main treatment period and 1 dose at the transition period.
Intervention Type
Biological
Intervention Name(s)
Denosumab
Intervention Description
Sterile, preservative-free, solution of denosumab packed in 1-mL pre-filled glass syringes for subcutaneous administration.Each syringe contains 60 mg denosumab (60 mg/mL solution) and is intended for single administration once every 6 months.
Primary Outcome Measure Information:
Title
To demonstrate equivalent efficacy between LY06006 and EU-Prolia, in terms of BMD in female participants with postmenopausal osteoporosis;
Description
%CfB in lumbar spine BMD at Month 12
Time Frame
12 months
Title
EU Marketing Authorization only: To demonstrate similar PD between LY06006 and EU-Prolia, in terms of the bone resorption marker sCTX in female participants with postmenopausal osteoporosis
Description
EU Marketing Authorization only: standardized AUEC0-6m (post first dose) of -%CfB in bone resorption marker sCTX over 6 months
Time Frame
6 months
Secondary Outcome Measure Information:
Title
To provide additional comparative efficacy data of LY06006 with EU-Prolia in female participants with postmenopausal osteoporosis
Description
%CfB in lumbar spine BMD at Month 6 %CfB in total hip BMD at Months 6 and 12 %CfB in femoral neck BMD at Months 6 and 12
Time Frame
6-12 months

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
lack of menstrual period for at least 12 months prior to Screening Visit, for which there is no other obvious pathological or physiological cause
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age Participant is ≥ 60 to ≤ 90 years of age inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics Participant is an ambulatory postmenopausal woman (defined as lack of menstrual period for at least 12 months prior to Screening Visit, for which there is no other obvious pathological or physiological cause). Serum FSH test can be done at the Screening Visit in case of uncertainty. Female participants who underwent bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior to the Screening Period are eligible to participate. Participant is diagnosed with osteoporosis, with absolute BMD consistent with a T-score of ≤ -2.5 and ≥ -4.0 at the lumbar spine (L1-L4 region) as measured by DXA at the Screening Visit. Participant has at least two lumbar vertebrae in L1-L4 region and one hip evaluable by DXA for BMD measurement at the Screening Visit. Weight 5. Participant has body weight ≥ 50 kg and ≤ 90 kg at Screening. Informed Consent 6. Participant is able to read and understand, and willing to provide signed informed consent as described in Appendix 1, Section 10.1.3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. - Exclusion Criteria: Medical Conditions Participant has a history and/or presence of any severe or more than two moderate vertebral fractures as determined by central reading of lateral spine X-ray at Screening Visit. Participant has a history and/or presence of hip fracture. Participant has a history and/or presence of atypical femur fracture. Participant presents with any active healing fracture, per assessment of the Investigator. Participant has a history of bilateral hip replacement (unilateral is allowed if the other hip is evaluable by DXA). Participant has history and/or presence of osteonecrosis of the external auditory canal. Evidence of any of the following conditions which may affect BMD or interfere with the interpretation of the findings: Participant has a history of bone disease e.g., osteomalacia, osteopetrosis, Paget's disease, or osteogenesis imperfecta. Participant has a history of metabolic or other endocrinologic diseases such as Cushing's disease, hyperprolactinemia, hypopituitarism, acromegaly, malabsorption syndrome (or any gastrointestinal disorders associated with malabsorption, e.g., Crohn's disease and chronic pancreatitis). Participant has a history of chronic inflammatory diseases, obvious sclerosis, osteophytosis, severe scoliosis, or other degenerative changes due to other co-morbidities. Participant has a history or current hyperparathyroidism or hypoparathyroidism. Note: Mild non-clinically significant secondary hyperparathyroidism may be acceptable upon discussion with the Medical Monitor. Participant has current uncontrolled hyperthyroidism or hypothyroidism. Note: Participants with hypothyroidism who are on stable thyroid hormone replacement therapy may be allowed per the following criteria: If TSH level is within normal range, the participant is eligible. If TSH level is elevated (> 5.5 μIU/mL and ≤ 10.0 μIU/mL) and serum free T4 is within normal range, the participant is eligible. If TSH is below the lower level of normal, the participant should be excluded. Participant has other disease conditions where there is bone/joint involvement (e.g., rheumatoid arthritis, ankylosing spondylitis, gout, multiple myeloma, achondroplasia, bone metastases, renal osteodystrophy, osteomyelitis). Participant has hypocalcemia (defined as albumin adjusted serum calcium level < 2.0 mmol/L [8.0 mg/dL] Grade 2 per Common Terminology Criteria for Adverse Events version 5.0) or hypercalcemia (defined as albumin adjusted serum calcium levels > 2.62 mmol/L [10.50 mg/dL]). Participant has vitamin D deficiency (defined as 25-hydroxy vitamin D level < 20 ng/mL [< 50 nmol/L]). Note: Oral replenishment of vitamin D is permitted at the discretion of the Investigator and in accordance with local standard of care during the Screening Period. Participants can be enrolled if a repeat test (post supplementation) prior to enrollment shows corrected 25-hydroxy vitamin D level ≥ 20 ng/mL (≥ 50 nmol/L). Participant has any malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years. Participant has known history of liver cirrhosis. Participant has known history of hepatitis B, hepatitis C, or HIV infection, or an active infection including, but not limited to SARS-CoV-2, tests positive for hepatitis B (positive HBsAg, positive anti-HBc with negative anti-HBs), hepatitis C (hepatitis C antibody), or HIV antibody during the Screening Period. Participant has oral or dental conditions: Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw. Active dental or jaw condition which requires oral surgery. Invasive dental procedure planned during the study or within the past 6 months (e.g., tooth extraction, dental implants, oral surgery). Non-healed dental or oral surgery. Active periodontal disease. Poor oral hygiene. Participant has a history of major surgery within 8 weeks prior to the Screening Period or planned, anticipated major surgery during the study. Participant has a history and/or presence of significant cardiac disease or ECG abnormalities indicating significant risk for participating in the study as judged by the Investigator. Prior/Concomitant Therapy Participant shows contraindications to denosumab therapy (e.g., hypocalcemia), or calcium or vitamin D supplementation before starting study intervention administration. Participant requires ongoing use of any osteoporosis treatment (other than calcium and vitamin D supplements). Use of any of the below medications that can affect BMD: l. Denosumab used at any time prior to Screening Visit. Oral bisphosphonates at any dose for osteoporosis treatment: Used for > 3 years cumulatively at Screening Visit. At any dose used within 1 year prior to Screening Visit (if ≤ 3 years of use cumulatively). Intravenous bisphosphonate at any dose within 5 years prior to Screening Visit. PTH or PTH analogues at any dose within 2 years prior to Screening Visit. Systemic HRT (oral or transdermal estrogen), SERMs, tibolone, aromatase inhibitors, or androgens at any dose within 1 year prior to Screening Visit. Note: Exceptionally, non-systemic vaginal estrogen treatment is permitted. Calcitonin, or its derivatives, and calcimimetics (such as cinacalcet or etelcalcetide) at any dose within 12 months prior to Screening Visit. Calcitriol, alfacalcidol, or eldecalcitol within 3 months of the Screening Visit. Fluoride or strontium at any dose at any time prior to Screening Visit. Romosozumab or cathepsin K inhibitors received at any time prior to Screening Visit. Systemic glucocorticoids (≥ 5 mg prednisone or equivalent per day for more than 10 days or cumulative ≥ 50 mg) within 3 months prior to Screening Visit. Other bone active drugs including anticonvulsants (except benzodiazepines, gabapentin, and pregabalin), heparin (including low molecular weight heparins), vitamin K (supplementation or therapeutic dose), vitamin K antagonists (e.g., warfarin, acenocumarol), emtricitabine, tenofovir, adefovir, systemic ketoconazole, adrenocorticotropic hormone, lithium, protease inhibitors, gonadotropin-releasing hormone agonist, aluminum, barbiturate, methotrexate, chemotherapeutic agents, cyclosporine, tacrolimus, or anabolic steroids at any dose within 3 months prior to Screening Visit. Prior/Concurrent Clinical Study Experience Participant is receiving or has received another investigational product within 1 month or 5 half-lives of the other investigational product, whichever is longer, before study intervention administration in this study. Diagnostic Assessments Participant has DXA measurements where: Height, weight, or girth measurements may preclude accurate DXA measurements in the Investigator's opinion. BMD absolute value is consistent with a T-score < -4.0 at the total hip or femoral neck. Participant has severe renal impairment (defined as participant in dialysis or with an eGFR < 30 mL/min per MDRD formula). Participant has inadequate hepatic function (ALT and/or AST ≥ 2 × ULN). Participant presents with clinically significant leukopenia, neutropenia, or anemia as judged by the Investigator. Other Exclusion Criteria Participant has a known intolerance to calcium or vitamin D supplements. Participant has a history of prescription drug abuse or any illicit drug use within 6 months prior to Screening Visit. Participant has a history of alcohol abuse (defined as consuming more than 3 drinks on any day or more than 7 drinks per week) according to medical history within 6 months prior to Screening Visit. Participant is a smoker or has used nicotine and nicotine-containing products within 12 months of Screening Visit. Participant has a known sensitivity to mammalian cell-derived drug products. Participant is immunosuppressed for any reason. Participant has any other conditions including clinically significant medical conditions/disorders/diseases, psychiatric status, or laboratory abnormalities that in the opinion of the Investigator might interfere with the participant's ability to participate in the study, would pose a risk to the participant's safety, or interfere with the study evaluation, procedure, or completion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maggie Wang, Master
Phone
0041 612068310
Ext
310
Email
maggie.wang@luyepharma.eu
Facility Information:
Facility Name
Shandong Boan Biotechnology Co., Ltd.
City
Yantai
State/Province
Shandong
ZIP/Postal Code
264670
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maggie Wang

12. IPD Sharing Statement

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Comparative Efficacy, Safety, PK, and Immunogenicity Study of LY06006 and EU-Prolia in Postmenopausal Women With Osteoporosis

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