A study of Denosumab in patients.

Phase 3

Not yet recruiting

• Conditions: Age-related osteoporosis without current pathological fracture,

• Registration Number: CTRI/2021/09/036190
• Lead Sponsor: Intas Pharmaceutical Limited Biopharma Division

Brief Summary

This is a randomized, double-blind, active-controlled, parallel-arm, multicenter study comparing the pharmacokinetics, pharmacodynamics, and immunogenicity of Denosumab of Intas (60 mg/ml) with Prolia, in postmenopausal women with osteoporosis aged 55 to 90 years, both inclusive.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-09-13
• Last Update Posted: 2023-03-29

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: Female
• Target Recruitment: 552

Inclusion Criteria

• 1.Participant must sign an ICF to participate in the study indicating that she understands the purpose of, and procedures required for the study as described in this protocol and is willing to and will be able to adhere to requirement of the protocol.
• 2.Participant must be 55 to 90 years of age (both inclusive), at the time of signing the informed consent.
• 3.Participants who are medically/clinically stable on the basis of physical examination, medical history, vital signs, chest x-ray PA view, 12-lead ECG and clinical laboratory parameters performed at screening.
• Any abnormalities or deviation from normal, must be consistent with the underlying illness in the study population and judged by investigator to be not clinically significant.
• This determination must be recorded in the participants source documents and initialed by the investigator.
• 4.Participants whose absolute bone mineral density T-score is less than equal to -2.5 and greater than equal -4.0 at the lumbar spine as measured by DXA (dual-energy x-ray absorptiometry), confirmed by the independent central imaging team 5.At least two vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA, confirmed by the independent central imaging team 6.Body weight between 50 kg and 90 kg (both inclusive) at screening.
• 7.Postmenopausal ambulatory female and not considered to be of child-bearing potential if: a.Women are considered post-menopausal and not of child-bearing potential if, i.They have had 12 months of natural (spontaneous) amenorrhea (no vaginal bleeding or spotting) with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) OR ii.Six months of spontaneous amenorrhea with serum FSH levels greater than 40 mIU per mL OR iii.Have had surgical bilateral oophorectomy (with or without hysterectomy) at least six months ago.
• In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she is considered not of child-bearing potential.

Exclusion Criteria

• 1.Documented medical history of clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances 2.Documented medical history of known allergies, hypersensitivity, or intolerance to denosumab or its excipients (refer to the IB) 3.History of any prior use of denosumab 4.Documented medical history of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as Pagets disease, osteomalacia, osteogenesis imperfecta, osteopetrosis, rheumatoid arthritis, ankylosing spondylitis or any other joint disease limiting mobility, Cushings disease, hyperprolactinemia, malabsorption syndrome 5.Documented medical history of latex or dry natural rubber allergy 6.Contraindications to the use of denosumab or Vitamin D and Calcium as per IB/local prescribing information at screening and/or baseline 7.Documented medical history and/or current evidence of any of the following oral/dental conditions a.Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw. b.Active dental or jaw condition which requires oral surgery. c.Planned invasive dental procedure expected during study period. d.Current evidence non-healed dental or oral surgery. e.Current evidence of poor oral hygiene f.Ill-fitting denture 8.Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range at screening. Serum calcium levels may be retested once in case of an elevated/low serum calcium level as assessed by the clinical laboratory. Final decision to include the patient based on the risk of hypocalcemia to be taken by the Investigator. 9.History of frequent occurrence of hypocalcemia, history of severe hypocalcemia or presence of diseases that can precipitate hypocalcemia frequently (like malabsorption syndromes (for example celiac disease, history of excision of small intestine etc.) and severe renal impairment) 10.Current, uncontrolled hyper- or hypoparathyroidism and history of hypoparathyroidism, per participant report or chart review. PTH outside the normal range (15-65 pg/mL) as assessed by central laboratory 11.Current, uncontrolled hyper- or hypothyroidism, defined as thyroid stimulating hormone outside of the normal range (TSH-0.465 to 4.68 mIU/L) at screening. 12.25 (OH) Vitamin D lower than 20 ng/mL as assessed by the central laboratory at Screening. Vitamin D repletion will be permitted, and participants may be rescreened once. 13.History of external beam or implant radiation therapy involving the skeleton. 14.History and /or presence of 1 severe fracture or 2 moderate vertebral fractures 15.Patients with bone metastases or a history of malignancies affecting bones. 16.Smokers or who have smoked within last 06 months prior to start of the study. 17.Documented medical history of major surgery, (e.g. requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate. 18.Documented medical history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening. 19.Documented medical history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening. 20.Documented medical history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before Screening 21.Lymphoma, leukemia, or any malignancy (current or suspected) within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence 22.QTc interval Greater than 470 msec or QT interval Greater than 480 msec in participants with bundle branch block. Note: The QTc is the QT interval corrected for heart rate according to Bazetts formula (QTcB). It is either machine-read or manually over-read. 23.Administration of bisphosphonate as follows:.
• c.IV Bisphosphonate in the past 3 years d.Oral bisphosphonates treatment for osteoporosis i.More than 3 years of cumulative use ii.Any dose received within 6 months prior to randomization iii.More than 1 month of cumulative use between 6 and 12 months prior to randomization 24.Teriparatide or any PTH analogs treatment received within 12 months prior to randomization. 25.Systemic oral or transdermal estrogen, SERMs, or calcitonin treatment of more than 1 month of cumulative use within 6 months prior to randomization. 26.Androgen deprivation or hormonal ablation therapy of more than 1 month of cumulative use within 6 months prior to randomization. 27.Tibolone or cinacalcet treatment received within 3 months prior to randomization 28.Systemic glucocorticoids: Greater than equal to 5 mg prednisone equivalent per day for more than 10 days within 3 months prior to randomization. 29.Abnormal laboratory values a.General: Any laboratory abnormality which, in the opinion of the Investigator, will prevent the patient from completing the study or interfere with the interpretation of the study results. b.Liver transaminases: i.Serum aspartate aminotransferase (AST) Greater than equal to3.0 in to upper limit of normal (ULN) ii.Serum alanine aminotransferase (ALT) Greater than equal to 3.0 in to ULN c.Alkaline phosphatase and bilirubin Greater than equal to 1.5 in to ULN d.Creatinine clearance estimated using Cockcroft Gault formula is less than30 mL/min 30.Taken any prohibited therapies as noted in Section 6.8, Concomitant Therapy before the planned first dose of study IMP 31.Received any investigational IMP 30 days or 5 half-lives (whichever is longer) before the signing the consent or is currently enrolled in an investigational study 32.Unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. This includes but is not limited to hepatitis virus infections, drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilsons disease, alpha-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator. Note: Stable chronic liver disease (including Gilberts syndrome, asymptomatic gallstones) is acceptable if the participant otherwise meets entry criteria. 33.Any other clinical/social/ psychiatric condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments 34.Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. If a participants clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study IMP is given such that he or she no longer meets all eligibility criteria, then the participant should be excluded from participation in the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
- To compare the pharmacodynamic effect of treatment with denosumab and denosumab-ref on bone mineral density (BMD) and bone resorption marker in postmenopausal women with osteoporosis	- Pharmacokinetics: Cmax, AUC0-t, and AUC0-infinity after first dose of denosumab and denosumab-ref | - Mean percentage change in BMD at lumbar spine from baseline to 12 months between denosumab and denosumab-ref | - Pharmacodynamics: Emax and AUEC0-t of % reduction from baseline serum C-terminal telopeptide (CTX) after first dose of denosumab and denosumab-ref
- To compare the pharmacokinetic parameters of denosumab and denosumab-ref in postmenopausal women with osteoporosis.	- Pharmacokinetics: Cmax, AUC0-t, and AUC0-infinity after first dose of denosumab and denosumab-ref | - Mean percentage change in BMD at lumbar spine from baseline to 12 months between denosumab and denosumab-ref | - Pharmacodynamics: Emax and AUEC0-t of % reduction from baseline serum C-terminal telopeptide (CTX) after first dose of denosumab and denosumab-ref

Secondary Outcome Measures

Name	Time	Method
To compare the efficacy of treatment with denosumab and denosumab-ref in postmenopausal women with osteoporosis	Incidence of clinical fracture between denosumab and denosumab-ref over 12 months.
To compare the pharmacodynamic effects of the treatment with denosumab and denosumab-ref in postmenopausal women with osteoporosis	Mean percentage change in bone mineral density (BMD) of lumbar spine from baseline to 06 months between denosumab and denosumab-ref
To compare the immunogenicity of denosumab and denosumab-ref in postmenopausal women with osteoporosis	Incidence of anti-denosumab antibody in denosumab and denosumab-ref arm over 12 months

Trial Locations

Locations (74)

7-Orange Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Aakash Healthcare Super speciality Hospital; 🇮🇳 Delhi, DELHI, India

ADITYA MULTI SPECIALITY HOSPITAL; 🇮🇳 Guntur, ANDHRA PRADESH, India

Ahmedabad Bariatrics & Cosmetics Pvt Ltd. (Asian Bariatrics Hospital); 🇮🇳 Ahmadabad, GUJARAT, India

Alexis Multi-Speciality Hospital Pvt. Ltd; 🇮🇳 Nagpur, MAHARASHTRA, India

Aman hospital and Research center; 🇮🇳 Vadodara, GUJARAT, India

Anand Surgical Hospital PVt Ltd.; 🇮🇳 Ahmadabad, GUJARAT, India

Ananta Institute of Medical Sciences & Research Centre; 🇮🇳 Rajsamand, RAJASTHAN, India

Asopa Hospital; 🇮🇳 Jaipur, RAJASTHAN, India

Aster Prime Hospital; 🇮🇳 Hyderabad, TELANGANA, India

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7-Orange Hospital

🇮🇳Pune, MAHARASHTRA, India

Dr Girish Bhatia

Principal investigator

8983377103

drgirishbhatia@gmail.com