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Clinical Efficacy and Safety Comparative Study Between CMAB807 Injection and Prolia® .

Primary Purpose

Postmenopausal Osteoporosis

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
CMAB807 Injection
Prolia®
Sponsored by
Shanghai Biomabs Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postmenopausal Osteoporosis

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Fully informed, understood, voluntary participate, and the patient himself or guardian agree to sign the written informed consent and patient be able to comply with the protocol;
  2. Aged from 50 years to 85 years, inclusive;
  3. Spontaneous amenorrhea time ≥ 2 years, or bilateral oophorectomy≥ 2 years. If the status of bilateral ovariectomies is unknown, the menopause status should be confirmed by follicle stimulating hormone(FSH) level≥ 40IU/L;
  4. Based on the results of dual energy X-ray absorptiometry, BMD of lumbar spine(L1~L4), femoral neck or total hip: -4.0<T-Score≤-2.5;
  5. There must be at least one of the following risk factors:

    • History of osteoporotic fracture;
    • Father's and mother's hip fracture history, or both parents';
    • Low body mass index(≤19kg/m^2);
    • Patient's age was equal or greater than 70 years old;
    • Current smoker;
    • CTX1 was one standard deviation higher than that of healthy premenopausal women within screening period(ie, CTX1>0.43ng/mL);
  6. Ability to act independently.

Exclusion Criteria:

  1. Suffering from the following diseases known to affect calcium or bone metabolism:

    • Various metabolic bone diseases, such as osteogenesis imperfecta and osteomalacia;
    • Paget's osteopathy;
    • Cushing's syndrome;
    • Hyperprolactinemia;
    • Hypopituitarism;
    • Acromegaly;
    • History of hyperparathyroidism or hypoparathyroidism;
    • History of hyperthyroidism or hypothyroidism(hypothyroidism patients can be included: only receiving stable thyroid hormone replacement therapy, if the thyroid stimulating hormone(TSH) level is normal, or 5.5μIU/mL<TSH≤10.0μIU/mL, and free thyroxine(FT4) is in normal range can be included);
    • Malabsorption syndrome or various gastrointestinal diseases associated with malabsorption, such as Crohn's disease and chronic pancreatitis;
    • Abnormal level of blood calcium: the current diagnosis of hypocalcemia or hypercalcemia or albumin corrected serum calcium levels are not within the laboratory normal range(calcium supplements should not be used for at least 8 hours prior to serum calcium testing);
    • Vitamin D deficiency: 25 hydroxyvitamin D concentration<20ng/mL. Allowed to retest after oral vitamin D2 soft capsules in the screening period. If the concentration of 25 hydroxyvitamin D is more than or equal to 20ng/mL, it can be selected;
    • Other diseases such as rheumatoid arthritis, gout, multiple myeloma, etc;
  2. Medical history of two or more vertebrae fractures;
  3. Malignant tumor(excluding skin basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ or breast ductal carcinoma in situ) in recent 5 years;
  4. Severe renal function damage(creatinine clearance rate<30mL/min), or dialysis, urinary calculi or chronic cystitis;
  5. Suffering from the following liver or biliary diseases:

    • Liver cirrhosis;
    • Biliary abnormalities(except for Gilbert syndrome or asymptomatic gallstones);
    • Positive hepatitis C virus antibody(HCV-Ab) and the titer of HCV-RNA exceeded the upper limit of norma;
    • Positive hepatitis B suface antigen(HBsAg) and peripheral blood HBV-DNA titer ≥1000 capies[CPS]/mL or 200IU/mL;
    • Unstable liver disease: defined as liver ascites, hepatic encephalopathy, coagulopathy, hypoalbuminemia, varicosis in esophagus or stomach fundus or persistent hepatic jaundice;
  6. Liver transaminase: aspartate aminotransferase≥2.0×upper limit of norma value(ULN), alanine aminotransferase≥2.0ULN, alkaline phosphatase≥1.5ULN or total bilirubin≥1.5ULN;
  7. Suffering from the following oral diseases:

    • Osteomyelitis or osteonecrosis of the jaw, previously or currently;
    • Actue dental or mandibular disease requiring stomatological surgery;
    • Planned invasive dental surgery during the trial period;
    • Dental or stomatological surgery have not healed;
  8. Conditions which can influence bone mineral density determination by dual energy X-ray absorptiometry:

    • Less than two lumbar vertebrae can be measured;
    • Height, weight or waistline may hinder accurate measurement;
    • Other conditions that may affect bone density testing
  9. Received anti-osteoporosis drugs or those drugs may affect bone metabolism:

    • Use of injectable bisphosphonates, fluoride or strontium within 2 years before screening;
    • Use of oral bisphosphonates: more than 2 years, or more than 3 months but less than 2 years and discontinued from last dosage less than 1 year, simultaneously;
    • Usage of any drugs which may affect bone metabolism within 6 weeks before screening: parathyroid hormone or parathyroid hormone analogue(such as teriparatide); assimilative hormone or testosterone; glucocorticoid(equivalent to prednisone>5mg/day for more than 10 days); systemic hormone replacement therapy; selective estrogen receptor regulator(such as reloxifene); tibolone; calcitonin; active vitamin D and ite analogues, other bone active drugs include anticonvulsant drugs(except benzodiazepines) and he[arin; long-term systemic use of ketoconazole, androgen, adrenocorticotropic hormone, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin releasing hormone agonist;
    • Patients who have received RANKL inhibitors previously;
  10. Positive HIV antibody;
  11. Known alcoholism or drug abuse(during 12 months before screening), because alcohol or drug abuse may interfere with subject's understanding or finish of trial;
  12. Known allergy to test drug, reference drug or basic drug and its excipients;
  13. Participate in interventionary clinical study(drug or device) within one month before screening;
  14. Other serious, acute or chronic diseases, mental disorders or laboratory abnormalities, which are judged by investigator to be unsuitable to participate this study.

Sites / Locations

  • Peking Union Medical College HosptialRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CMAB807

Prolia®

Arm Description

60mg, every 6 months, subcutaneously for twice. dietary supplement: elemental calcium orally, 600mg, daily, and vitamin D orally, 400IU, daily

60mg, every 6 months, subcutaneously for twice. dietary supplement: elemental calcium orally, 600mg, daily, and vitamin D orally, 400IU, daily

Outcomes

Primary Outcome Measures

BMD percentage change from baseline at lumbar spine(L1~L4)
Percentage change from baseline at lumbar spine(L1~L4) by dual-energy X-ray absorptiometry to month 12 of treatment and compare between two arms. Percentage change of lumbar spine BMD from baseline to at month 12 of treatment=(BMD at month 12 of treatment - BMD at baseline)/BMD at baseline*100%

Secondary Outcome Measures

BMD percentage change from baseline at lumbar spine(L1~L4)
Percentage change from baseline at lumbar spine(L1~L4) by dual-energy X-ray absorptiometry to month 6 of treatment and compare between two arms. Percentage change of lumbar spine BMD from baseline to at month 12 of treatment=(BMD at month 12 of treatment - BMD at baseline)/BMD at baseline*100%
BMD percentage change from baseline at total hip, trochanter and femoral neck
Pencentage change from baseline at total hip, trochanter and fremoral neck by dual-energy-X-ray absorptiometry to month 6 and month 12 of treatment, and compare between two arms. Percentage to total hip, trochanter and femoral neck BMD from baseline at month 6 or month 12 of treatment=(BMD at month 6 or month 12 of treatment - BMD at baseline)/BMD at baseline*100%
Serum CTX1 and P1NP concentration percentage change from baseline
Fasting serum CTX1 and P1NP samples should be collected. Percentage changes of serum CTX1 or P1NP concentrations from baseline at month 1, month 3, month 6, month 9 and at month 12 of treatment=(serum concentrations at month 1, month 3, month 6, month 9 and month 12 - serum concentration at baseline)/serum concentration at baseline*100%
Proporation of new osteoporotic fractures(vertebrae, total hip and non-vertebrae) occurring within the study period
Osteoporotic fracture is defined as the fracture occurred when subject suffers minor trauma or during daily activities. Common occurrence sites are vertebral body, hip, distal forearm, proximal humerus and pelvis, etc
Adeverse events and serious adverse events
Evaluation of the drug reactions, changes in physical examination findings, changes in vital signs, stomatological examination, clinical laboratory testing for systemic safety(including complete blood count, urinalysis, clinical chemistries, coagulation function, liver function, renal function, parathyroid function), and electrocardiography
Immunogenicity
Binding antibody and neutralizing antibody formation assays were used to assess number of subjects with anti-denosumab antibody
Population pharmacokinetics analysis
The pharmacokinetic parameters were described statistically, such as population typical value of clearance rate, estimation precision of typical value, confindence interval of typical value, and inter individual variation

Full Information

First Posted
October 15, 2020
Last Updated
April 26, 2023
Sponsor
Shanghai Biomabs Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04591275
Brief Title
Clinical Efficacy and Safety Comparative Study Between CMAB807 Injection and Prolia® .
Official Title
Randomized, Doubel-blinded, Parallel, Active-controlled Phase III Study, to Evaluate the Efficacy and Safety of CMAB807 Treatment Compared With Prolia® in Chinese Postmenopausal Women With Osteoporosis at High Risk of Fracture.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2021 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
November 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Biomabs Pharmaceutical Co., Ltd.

4. Oversight

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

5. Study Description

Brief Summary
evaluate the differences in effectiveness and safety between CMAB807( potential biosimilar) and Prolia(original product)
Detailed Description
this is a randomized, double-blinded, parallel, active-controlled clinical phase III study. the primary objective is to evaluate the efficacy and safety of CMAB807 treatment compared with Prolia in Chinese postmenopausal women with osteoporosis at high risk of fracture. Subjects should sequentially enrolled according to the protocol in one of two arms. Subjects who entered in test arm would receive 60mg of CMAB807 subcutaneously every 6 months for one year, while those who entered in control arm should receive 60mg of Prolia subcutaneously every 6 months for one year. Meanwhile, every subject should taking 600mg calcium and 400IU vitamin D daily from successfully screening to the end of study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal Osteoporosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
278 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CMAB807
Arm Type
Experimental
Arm Description
60mg, every 6 months, subcutaneously for twice. dietary supplement: elemental calcium orally, 600mg, daily, and vitamin D orally, 400IU, daily
Arm Title
Prolia®
Arm Type
Active Comparator
Arm Description
60mg, every 6 months, subcutaneously for twice. dietary supplement: elemental calcium orally, 600mg, daily, and vitamin D orally, 400IU, daily
Intervention Type
Drug
Intervention Name(s)
CMAB807 Injection
Other Intervention Name(s)
Denosumab Injection
Intervention Description
mAb targeting RANKL, human monoclonal antibody targeting RANKL
Intervention Type
Drug
Intervention Name(s)
Prolia®
Other Intervention Name(s)
Denosumab Injection
Intervention Description
mAb targeting RANKL, human monoclonal antibody targeting RANKL
Primary Outcome Measure Information:
Title
BMD percentage change from baseline at lumbar spine(L1~L4)
Description
Percentage change from baseline at lumbar spine(L1~L4) by dual-energy X-ray absorptiometry to month 12 of treatment and compare between two arms. Percentage change of lumbar spine BMD from baseline to at month 12 of treatment=(BMD at month 12 of treatment - BMD at baseline)/BMD at baseline*100%
Time Frame
baseline, at 12 months
Secondary Outcome Measure Information:
Title
BMD percentage change from baseline at lumbar spine(L1~L4)
Description
Percentage change from baseline at lumbar spine(L1~L4) by dual-energy X-ray absorptiometry to month 6 of treatment and compare between two arms. Percentage change of lumbar spine BMD from baseline to at month 12 of treatment=(BMD at month 12 of treatment - BMD at baseline)/BMD at baseline*100%
Time Frame
baseline, at 6 months
Title
BMD percentage change from baseline at total hip, trochanter and femoral neck
Description
Pencentage change from baseline at total hip, trochanter and fremoral neck by dual-energy-X-ray absorptiometry to month 6 and month 12 of treatment, and compare between two arms. Percentage to total hip, trochanter and femoral neck BMD from baseline at month 6 or month 12 of treatment=(BMD at month 6 or month 12 of treatment - BMD at baseline)/BMD at baseline*100%
Time Frame
baseline, at month 6, at month 12
Title
Serum CTX1 and P1NP concentration percentage change from baseline
Description
Fasting serum CTX1 and P1NP samples should be collected. Percentage changes of serum CTX1 or P1NP concentrations from baseline at month 1, month 3, month 6, month 9 and at month 12 of treatment=(serum concentrations at month 1, month 3, month 6, month 9 and month 12 - serum concentration at baseline)/serum concentration at baseline*100%
Time Frame
baseline, at month 1, at month 3, at month 6, at month 9,and at month 12
Title
Proporation of new osteoporotic fractures(vertebrae, total hip and non-vertebrae) occurring within the study period
Description
Osteoporotic fracture is defined as the fracture occurred when subject suffers minor trauma or during daily activities. Common occurrence sites are vertebral body, hip, distal forearm, proximal humerus and pelvis, etc
Time Frame
baseline, at month 12
Title
Adeverse events and serious adverse events
Description
Evaluation of the drug reactions, changes in physical examination findings, changes in vital signs, stomatological examination, clinical laboratory testing for systemic safety(including complete blood count, urinalysis, clinical chemistries, coagulation function, liver function, renal function, parathyroid function), and electrocardiography
Time Frame
baseline ,at 12 months
Title
Immunogenicity
Description
Binding antibody and neutralizing antibody formation assays were used to assess number of subjects with anti-denosumab antibody
Time Frame
baseline, at 12 months
Title
Population pharmacokinetics analysis
Description
The pharmacokinetic parameters were described statistically, such as population typical value of clearance rate, estimation precision of typical value, confindence interval of typical value, and inter individual variation
Time Frame
baseline, at 12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Fully informed, understood, voluntary participate, and the patient himself or guardian agree to sign the written informed consent and patient be able to comply with the protocol; Aged from 50 years to 85 years, inclusive; Spontaneous amenorrhea time ≥ 2 years, or bilateral oophorectomy≥ 2 years. If the status of bilateral ovariectomies is unknown, the menopause status should be confirmed by follicle stimulating hormone(FSH) level≥ 40IU/L; Based on the results of dual energy X-ray absorptiometry, BMD of lumbar spine(L1~L4), femoral neck or total hip: -4.0<T-Score≤-2.5; There must be at least one of the following risk factors: History of osteoporotic fracture; Father's and mother's hip fracture history, or both parents'; Low body mass index(≤19kg/m^2); Patient's age was equal or greater than 70 years old; Current smoker; CTX1 was one standard deviation higher than that of healthy premenopausal women within screening period(ie, CTX1>0.43ng/mL); Ability to act independently. Exclusion Criteria: Suffering from the following diseases known to affect calcium or bone metabolism: Various metabolic bone diseases, such as osteogenesis imperfecta and osteomalacia; Paget's osteopathy; Cushing's syndrome; Hyperprolactinemia; Hypopituitarism; Acromegaly; History of hyperparathyroidism or hypoparathyroidism; History of hyperthyroidism or hypothyroidism(hypothyroidism patients can be included: only receiving stable thyroid hormone replacement therapy, if the thyroid stimulating hormone(TSH) level is normal, or 5.5μIU/mL<TSH≤10.0μIU/mL, and free thyroxine(FT4) is in normal range can be included); Malabsorption syndrome or various gastrointestinal diseases associated with malabsorption, such as Crohn's disease and chronic pancreatitis; Abnormal level of blood calcium: the current diagnosis of hypocalcemia or hypercalcemia or albumin corrected serum calcium levels are not within the laboratory normal range(calcium supplements should not be used for at least 8 hours prior to serum calcium testing); Vitamin D deficiency: 25 hydroxyvitamin D concentration<20ng/mL. Allowed to retest after oral vitamin D2 soft capsules in the screening period. If the concentration of 25 hydroxyvitamin D is more than or equal to 20ng/mL, it can be selected; Other diseases such as rheumatoid arthritis, gout, multiple myeloma, etc; Medical history of two or more vertebrae fractures; Malignant tumor(excluding skin basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ or breast ductal carcinoma in situ) in recent 5 years; Severe renal function damage(creatinine clearance rate<30mL/min), or dialysis, urinary calculi or chronic cystitis; Suffering from the following liver or biliary diseases: Liver cirrhosis; Biliary abnormalities(except for Gilbert syndrome or asymptomatic gallstones); Positive hepatitis C virus antibody(HCV-Ab) and the titer of HCV-RNA exceeded the upper limit of norma; Positive hepatitis B suface antigen(HBsAg) and peripheral blood HBV-DNA titer ≥1000 capies[CPS]/mL or 200IU/mL; Unstable liver disease: defined as liver ascites, hepatic encephalopathy, coagulopathy, hypoalbuminemia, varicosis in esophagus or stomach fundus or persistent hepatic jaundice; Liver transaminase: aspartate aminotransferase≥2.0×upper limit of norma value(ULN), alanine aminotransferase≥2.0ULN, alkaline phosphatase≥1.5ULN or total bilirubin≥1.5ULN; Suffering from the following oral diseases: Osteomyelitis or osteonecrosis of the jaw, previously or currently; Actue dental or mandibular disease requiring stomatological surgery; Planned invasive dental surgery during the trial period; Dental or stomatological surgery have not healed; Conditions which can influence bone mineral density determination by dual energy X-ray absorptiometry: Less than two lumbar vertebrae can be measured; Height, weight or waistline may hinder accurate measurement; Other conditions that may affect bone density testing Received anti-osteoporosis drugs or those drugs may affect bone metabolism: Use of injectable bisphosphonates, fluoride or strontium within 2 years before screening; Use of oral bisphosphonates: more than 2 years, or more than 3 months but less than 2 years and discontinued from last dosage less than 1 year, simultaneously; Usage of any drugs which may affect bone metabolism within 6 weeks before screening: parathyroid hormone or parathyroid hormone analogue(such as teriparatide); assimilative hormone or testosterone; glucocorticoid(equivalent to prednisone>5mg/day for more than 10 days); systemic hormone replacement therapy; selective estrogen receptor regulator(such as reloxifene); tibolone; calcitonin; active vitamin D and ite analogues, other bone active drugs include anticonvulsant drugs(except benzodiazepines) and he[arin; long-term systemic use of ketoconazole, androgen, adrenocorticotropic hormone, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin releasing hormone agonist; Patients who have received RANKL inhibitors previously; Positive HIV antibody; Known alcoholism or drug abuse(during 12 months before screening), because alcohol or drug abuse may interfere with subject's understanding or finish of trial; Known allergy to test drug, reference drug or basic drug and its excipients; Participate in interventionary clinical study(drug or device) within one month before screening; Other serious, acute or chronic diseases, mental disorders or laboratory abnormalities, which are judged by investigator to be unsuitable to participate this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
weibo Xia, Doctor
Phone
13501002126
Email
weiboxia@sohu.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
weibo Xia, Doctor
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hosptial
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

Clinical Efficacy and Safety Comparative Study Between CMAB807 Injection and Prolia® .

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