CTRI/2023/09/057671 [Registered on: 15/09/2023] Trial Registered Prospectively
Last Modified On:
14/05/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A Study to assess effectiveness and safety of Lupin’s Denosumab (IRO2201A/LUBT014) compared to Prolia®
Scientific Title of Study
A multi-center, randomized, double blind, parallel group, phase III study to evaluate efficacy, safety, and immunogenicity of Lupin’s Denosumab (IRO2201A/LUBT014) in comparison with Prolia® in postmenopausal women with osteoporosis.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
IRO2201A301 Version 2.1 Dated 12 April 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Chirag Shah
Designation
Director
Affiliation
Lupin Limited
Address
Lupin Research Park, Survey No 46A 47A Village Nande Tal Mulshi, Pune. Lupin Research Park, Survey No 46A 47A Village Nande Tal Mulshi, Pune.
Pune MAHARASHTRA 412115 India
Institutional Ethics Committee Visakha Institute of Medical Sciences
Approved
Institutional Human Ethics Committee Panimalar Medical College Hospital and Research Institute
Approved
Lifepoint Research Ethics Committee
Approved
Medilink Ethics Committe
Approved
Medstar Speciality Hospital Ethics Committee
Approved
NIMS Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: Q782||Osteopetrosis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Lupin’s Denosumab
Lupin’s Denosumab 60 mg solution for injection (60 mg/mL) in pre-filled syringe administered as subcutaneous injection at day 0 and month 6 of the study.
Comparator Agent
Prolia
Prolia® 60 mg solution for injection (60 mg/mL) in pre-filled syringe administered as subcutaneous injection at day 0 and month 6 of the study.
Inclusion Criteria
Age From
55.00 Year(s)
Age To
80.00 Year(s)
Gender
Female
Details
1. Postmenopausal women with osteoporosis. A woman is
considered postmenopausal if she meets any of the following
criteria:
• Lack of menstrual period for at least 12 months prior to screening,
for which there is no other pathological or physiological cause.
• Have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six months ago.
(Serum follicle stimulating hormone [FSH] and serum estradiol level
tests can be done at screening in case of uncertainty.)
2. Age ≥ 55 and ≤ 80 years at the time of informed consent.
3. Absolute bone mineral density consistent with T-score ≤ -2.5 and
≥ -4.0 at the lumbar spine as measured by Dual-energy X-ray
absorptiometry (DXA).
4. At least two vertebrae in the L1-L4 region and at least one hip joint are evaluable by DXA.
5. Patients willing to provide written informed consent.
ExclusionCriteria
Details
1. Body weight of ≤ 45 kg and ≥ 95 kg at screening.
2. Presence of one severe or more than two moderate vertebral
fractures as determined by spine X-ray during the screening
period.
3. Inadequate renal function at the screening defined as patient on
dialysis or estimated glomerular filtration rate (eGFR)
< 30 mL/min.
4. Presence of clinically significant leukopenia, neutropenia, or
anaemias judged by the investigator.
5. Prior denosumab and strontium or fluoride administration.
6. Ongoing and/or prior administration of the following medicines
for osteoporosis:
a. Intravenous bisphosphonates: dose received within 5 years
prior to screening.
b. Oral bisphosphonates used > 3 years cumulative use, and any
dose within 12 months of screening.
c. Teriparatide or any parathyroid hormones (PTH) analogues:
dose received within 6 weeks prior to screening.
d. Tibolone, oral, or topical (e.g., transdermal, intravaginal)
estrogen, selective estrogen receptor modulators (SERMs):
dose received within 6 weeks prior to screening.
e. Calcitonin: dose received within 6 weeks prior to screening.
f. Active Vitamin D dose received within 2 weeks prior to
screening.
7. Systemic glucocorticosteroids (≥ 5 mg prednisone equivalent per
day for ≥ 10 days or a total cumulative dose of ≥ 50 mg) within the
past 3 months before screening.
8. Other bone active drugs (i.e., drugs affecting bone metabolism)
including heparin, anti-epileptics (except for benzodiazepines and
pregabalin), systemic ketoconazole, adrenocorticotrophic
hormone (ACTH), lithium, protease inhibitors, gonadotropinreleasing
hormone (GnRH) agonists, or anabolic steroids within
the past 3 months prior to screening.
9. Receiving or has received any investigational drug (or is currently
using an investigational device) within 3 months before receiving
IMP, or at least 10 times the respective elimination half-life
(whichever period is longer).
10. Abnormal serum calcium (re-test and rescreening is permitted):
current hypocalcemia (< 8.4 mg/dL).
11. Abnormal serum calcium (re-test and rescreening is permitted):
current hypocalcemia (< 8.4 mg/dL).
12. Vitamin D deficiency (25-hydroxy vitamin D levels cut-off at
< 12 ng/mL) at screening. (Vitamin D repletion/re-test and
rescreening is permitted).
13. History and/or presence of following bone conditions: bone
metastases, renal osteodystrophy, Paget’s disease, osteogenesis
imperfect, osteopetrosis, osteomyelitis, Pott’s disease
(tuberculosis of spine), Cushing’s syndrome.
14. Current or prior use of romosozumab or antisclerostin antibody.
15. Current hypoparathyroidism or hyperparathyroidism other than
clinically not significant secondary hyperparathyroidism as judged
by the investigator.
16. Major surgery within 8 weeks before screening or planned,
anticipated major surgery during the study.
17. History and/or presence of malignancy (except completely cured
in situ cervical carcinoma or non-metastatic squamous or basal cell
carcinoma of the skin). Patient with history of malignancy without
recurrence for more than 5 years can be included.
18. History and/or presence of significant cardiac disease as judged by
the investigator.
19. Known intolerance to or malabsorption of calcium or Vitamin D.
20. Known hypersensitivity of monoclonal antibodies or history of
systemic hypersensitivity to any component of the IMPs.
21. Contraindications to denosumab therapy (e.g., hypocalcaemia), or
calcium or vitamin D supplementation before starting the IMP
administration.
22. Known allergic reactions, hypersensitivity, or intolerance to
denosumab or to any ingredients of the IMP, including latex
allergy.
23. Patient with seropositivity for human immunodeficiency virus
infections at the time of screening.
24. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as
invasive dental procedures (e.g., tooth extraction, dental implants,
oral surgery in the past 6 months), poor oral hygiene, periodontal,
and/or pre-existing dental disease as assessed by the Investigator.
25. Any other clinically significant disorder/condition/disease or lab
abnormality that in the opinion of the investigator would pose a
risk to subject safety or interfere with the study evaluation,
procedures, or completion.
26. Patients with confirmed COVID-19 infection within a month prior
to screening.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Percent change from baseline in Bone Mineral Density (BMD) at the lumbar spine at Month 12.
Note: L1-L4 region should be included.
12 months
Secondary Outcome
Outcome
TimePoints
1 Efficacy Endpoints
Percent change from baseline in BMD at the lumbar spine at Month 6
Percent change from baseline in BMD at the total hip & femoral neck at Month 6 & Month 12.
2 Safety Endpoint
Number of patients with treatment emergent adverse events (TEAEs) & Serious adverse events (SAEs).
3 Immunogenicity Endpoint
Proportion of patients with treatment emergent anti-Denosumab antibodies (binding & neutralizing) at month 3, 6, 9, & 12.
4 Pharmacokinetic Endpoint
Descriptive (pharmacokinetic [PK]) assessment of Serum Denosumab concentration.
3, 6, 9 & 12 months
Target Sample Size
Total Sample Size="400" Sample Size from India="150" Final Enrollment numbers achieved (Total)= "453" Final Enrollment numbers achieved (India)="100"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
A multi-center, randomized, double blind, parallel group, phase III study to evaluate efficacy, safety, and immunogenicity of Lupin’s Denosumab (IRO2201A/LUBT014) in comparison with Prolia® in postmenopausal women with osteoporosis. Approximately 150 patients are planned to be enrolled in the study