Denosumab Biosimilar Injection in Post Menopausal Women With Osteoporosis

NCT05419427 | Unknown Phase 3 FDA Drug

• 2 other identifiers: 0774-19CTRI/2021/09/036190
• Study Type: interventional
• Target: 552
• Locations: 1 country
• Sites: 1

Brief Summary

Denosumab of Intas is biosimilar denosumab candidate under development by Intas Pharmaceutical Limited (Biopharma Division). Denosumab of Intas is already approved by Indian drug licensing authority- Drug Controller General (India) for marketing in Indian population since 2018.As per regulatory requirement, a comparative clinical study to establish Pharmacokinetic, Pharmacodynamic and Immunogenicity equivalence is required to conclude therapeutic equivalence to obtain marketing authorization of a biosimilar investigational product. This is a multicenter, randomized, double-blind, active controlled study in approximately 552postmenopausal women with osteoporosis. An extension of the study is planned after completion of the initial 1 year of treatment. This extension is with the objective of submitting data on safety, and Immunogenicity, after switching of Prolia treatment arm to either Prolia or Intas denosumab for 6 months. This switching data is applicable only for FDA submission. Only patients who have undergone PK assessment will be eligible for the extension phase.

Conditions

Osteoporosis, Postmenopausal

Outcome Measures

Primary Outcomes (3)

• Maximum measured concentration after first dose of denosumab and denosumab-ref., ,

  Day 1 to Day 181

• Area under the concentration versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method between denosumab and denosumab-ref postmenopausal women with osteoporosis

  Day 1 to Day 181

• Area under the concentration versus time curve from time zero to infinity. Where AUC 0-∞= AUC0-t + Ct2, Ct is the last measurable concentration and t2 is the terminal rate constant

  Day 1 to Day 181

Secondary Outcomes (2)

• Maximum percent reduction from baseline Emax percent reduction from baseline serum C-terminal telopeptide (CTX) after first dose of denosumab and denosumab-ref*

  Day 1 to Day 181

• Area under the percent reduction from baseline versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method

  Day 1 to Day 181

Study Arms (2)

Denosumab Solution for injection in single use prefilled syringe 60 mg permL

EXPERIMENTAL

Unit Dose Strength 60 mg per mL,Dosage Level 60 mg once every 6 months, Route of Administration-Subcutaneous injection

Drug: Denosumab

Prolia® Solution for injection in single use prefilled syringe 60 mg per mL

ACTIVE COMPARATOR

Unit Dose Strength 60 mg per mL,Dosage Level 60 mg once every 6 months,Route of Administration-Subcutaneous injection

Drug: Denosumab-Ref

Interventions

Denosumab DRUG

Denosumab 60 MG/ML

Also known as: INTP23

Denosumab Solution for injection in single use prefilled syringe 60 mg permL

Denosumab-Ref DRUG

Denosumab 60 MG/ML

Also known as: Prolia

Prolia® Solution for injection in single use prefilled syringe 60 mg per mL

Eligibility Criteria

• Age: 55 Years - 90 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Participant must be 55 to 90 years of age (both inclusive), at the time of signing the informed consent.
• 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
• 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.
• 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

You may not qualify if:

• Documented medical history of clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• Documented medical history of known allergies, hypersensitivity, or intolerance to denosumab or its excipients (refer to the IB)
• 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
• Contraindications to the use of denosumab or Vitamin D and Calcium as per IB/local prescribing information at screening and/or baseline
• Documented medical history and/or current evidence of any of the following oral/dental conditions
• Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw.
• Active dental or jaw condition which requires oral surgery.
• Planned invasive dental procedure expected during study period.
• Current evidence non-healed dental or oral surgery.
• Current evidence of poor oral hygiene
• Ill-fitting denture
• Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range at screening.
• 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
• 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.
• (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.

Sponsors & Collaborators

• Lambda Therapeutic Research Ltd.: lead
• Intas Pharmaceutical Limited (Biopharma Division): collaborator

Study Sites (1)

S. R. Kalla Memorial Gastro & General Hospital

Jaipur, Rajasthan, 302001, India

RECRUITING

MeSH Terms

Conditions

Osteoporosis, Postmenopausal

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Mr Prashant Modi

CONTACT

917940202375; prashantmodi@lambda-cro.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: double-blinded. Participant, Investigator and Outcomes Assessor are masked
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: June 15, 2022
• Study Start: November 11, 2021
• Primary Completion: September 11, 2024
• Study Completion: November 24, 2024
• Last Updated: October 13, 2023

Record last verified: 2023-10

Locations

IN (1)