A multi-center, randomized, double blind, parallel group, phase III study to evaluate efficacy, safety and immunogenicity of Lupins Denosumab in comparison with Prolia in postmenopausal women with osteoporosis.
Evaluation of efficacy, safety and immunogenicity of Lupins Denosumab compared to Prolia in postmenopausal women with osteoporosis.
Sakine Michitoshi
ID Pharma Co., Ltd.
2-10-2, Fujimi, Tiyoda-ku, Tokyo
+81-92-406-8278
michitoshi-sekine@iromgroup.co.jp
Sakine Michitoshi
ID Pharma Co., Ltd.
2-10-2, Fujimi, Tiyoda-ku, Tokyo
+81-92-406-8278
michitoshi-sekine@iromgroup.co.jp
Recruiting
June. 07, 2023
400
Interventional
randomized controlled trial
double blind
active control
parallel assignment
other
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.
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>3years 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(>=5mg prednisone equivalent per day for>=10 days or a total cumulative dose of=>50mg)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, gonadotropin-releasing 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.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).
12.History and/or presence of following bone conditions:bone metastases,renal osteodystrophy,Pagets disease,osteogenesis imperfect,osteopetrosis,osteomyelitis,Potts disease(tuberculosis of spine),Cushings syndrome.
13.Current or prior use of romosozumab or antisclerostin antibody.
14.Current hypoparathyroidism or hyperparathyroidism other than clinically not significant secondary hyperparathyroidism as judged by the investigator.
15.Major surgery within 8 weeks before screening or planned, anticipated major surgery during the study.
16.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.
17.History and/or presence of significant cardiac disease as judged by the investigator.
18.Known intolerance to or malabsorption of calcium or Vitamin D.
19.Known hypersensitivity of monoclonal antibodies or history of systemic hypersensitivity to any component of the IMPs.
20.Contraindications to denosumab therapy(e.g.,hypocalcaemia),or calcium or vitamin D supplementation before starting the IMP administration.
21.Known allergic reactions,hypersensitivity,or intolerance to denosumab or to any ingredients of the IMP,including latex allergy.
22.Patient with seropositivity for human immunodeficiency virus infections at the time of screening.
23.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.
24.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.
25.Patients with confirmed COVID-19 infection within a month prior to screening.
55age old over
80age old under
Female
Osteoporosis
A:Each pre-filled syringe contains 60 mg of denosumab in 1 mL of solution (60 mg/mL) administered once in every six months subcutaneously
B:Each pre-filled syringe contains 60 mg of denosumab in 1 mL of solution (60 mg/mL) administered once in every six months subcutaneously
Percent change from baseline in Bone Mineral Density (BMD) at the lumbar spine at Month 12.
Note: L1-L4 region should be included.
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 and femoral neck at Month 6 and Month 12.
Safety Endpoint
Number of patients with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs).
Immunogenicity Endpoint
Proportion of patients with treatment emergent anti-denosumab antibodies (binding and neutralizing) at month 3, 6, 9, and 12.
Pharmacokinetic Endpoint (To be conducted only in Japan)
Descriptive (pharmacokinetic [PK]) assessment of Serum denosumab concentration.
ID Pharma Co., Ltd.
HURECS (Review Board of Human Rights and Ethics for Clinical Studies)
2-2-1, Kyoubasi, Cyuou-ku, Tokyo, Japan, Tokyo
April. 22, 2023
Yes
We are planning to share individual subject data coded with patient identification code.
