Biosimilar denosumab injection for postmenopausal women with osteoporosis

A Randomized,Double Blind,Active Controlled Parallel Arm Multicenter Study Comparing Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Denosumab of Intas Pharmaceutical Limited (60 mg/mL) With Prolia® in Postmenopausal Women With Osteoporosis

This study is testing a new version of a medication for osteoporosis in postmenopausal women to see if it works as well as the original treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 552 (estimated)
• Ages: 55 Years to 90 Years
• Sex: Female
• Sponsor: Lambda Therapeutic Research Ltd. (Industry-sponsored)
• Drugs / interventions: denosumab, prednisone
• Locations: 1 site (Jaipur, Rajasthan)
• Trial ID: NCT05419427 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates a biosimilar version of denosumab, developed by Intas Pharmaceutical Limited, in postmenopausal women diagnosed with osteoporosis. The study is a multicenter, randomized, double-blind, active-controlled trial involving approximately 552 participants. It aims to establish pharmacokinetic, pharmacodynamic, and immunogenicity equivalence to the original denosumab treatment. Following the initial year of treatment, an extension phase will assess safety and immunogenicity after switching treatment arms. This research is crucial for obtaining marketing authorization for the biosimilar in the U.S.

Who should consider this trial

Good fit: Ideal candidates for this study are postmenopausal women aged 55 to 90 with a bone mineral density T-score between -2.5 and -4.0.

Not a fit: Patients who are not postmenopausal or those with a T-score above -2.5 or below -4.0 will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide an effective and potentially more affordable treatment option for postmenopausal women suffering from osteoporosis.

How similar studies have performed: Other studies on biosimilars have shown success in establishing therapeutic equivalence, suggesting a positive outlook for this approach.

Eligibility criteria

Key Inclusion Criteria

* 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

Key Exclusion Criteria:

* 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

  1. Prior history or current evidence of osteomyelitis or osteonecrosis of the jaw.
  2. Active dental or jaw condition which requires oral surgery.
  3. Planned invasive dental procedure expected during study period.
  4. Current evidence non-healed dental or oral surgery.
  5. Current evidence of poor oral hygiene
  6. 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.
* 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.
* History and /or presence of 1 severe fracture or 2 moderate vertebral fractures
* Smokers or who have smoked within last 06 months prior to start of the study.
* 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
* Teriparatide or any PTH analogs treatment received within 12 months prior to randomization.
* Systemic oral or transdermal estrogen, SERMs, or calcitonin treatment of more than 1 month of cumulative use within 6 months prior to randomization.
* Androgen deprivation or hormonal ablation therapy of more than 1 month of cumulative use within 6 months prior to randomization.
* Tibolone or cinacalcet treatment received within 3 months prior to randomization
* Systemic glucocorticoids: Greater than equal to 5 mg prednisone equivalent per day for more than 10 days within 3 months prior to randomization.

Where this trial is running

Jaipur, Rajasthan

• S. R. Kalla Memorial Gastro & General Hospital — Jaipur, Rajasthan, India (Recruiting)

Study contacts

• Study coordinator: Mr Prashant Modi

Conditions Osteoporosis, Postmenopausal