Osteoporosis MedDRA version: 20.0 Level: PT Classification code 10031282 Term: Osteoporosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: denosumab
Product Code: AVT03
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Denosumab
CAS Number: 615258-40-7
Current Sponsor code: AVT03
Concent
Sponsors
Alvotech Swiss AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Postmenopausal women with osteoporosis willing to sign an informed consent form and able to undergo protocol related procedures. 2.Age: =50 years. 3.Female subject is postmenopausal according to 1 of the following criteria: a.Spontaneous amenorrhea for =12 consecutive months b.Biochemical criteria of menopause, follicle-stimulating hormone, >40 IU/L except surgically sterile c.Having had bilateral oophorectomy =6 weeks prior to Screening 4.Body Mass Index: 18.5-32.0 kg/m2 5.A baseline dual-energy x-ray absorptiometry scan with a T-score =-2.5 and = -4.0 at the lumbar spine (LS) (L1 to L4) and/or total hip and/or femoral neck. A subject must have a T score within the stated range of = -2.5 and = -4.0 in at least 1 of the 3 areas: - Lumbar spine (L1 to L4) - Total hip - Femoral neck. On the contrary, subjects will be excluded from the trial if the T score is less than -4.0 in at least 1 of the 3 areas (ie, at the LS [L1 to L4], or total hip, or femoral neck). Note: The left hip should be scanned for the calculation of total hip T score. If the left hip cannot be scanned (eg, due to left hip replacement, etc), the right hip can be scanned instead. The same hip should be used for all dual-energy x-ray absorptiometry scans. 6.At least 2 consecutive evaluable lumbar vertebrae and at least 1 evaluable hip. 7.Willing to receive calcium plus vitamin D supplements. 8.No history or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the Investigator, would pose a risk to subject safety. 9.Resting supine systolic blood pressure of =150 mmHg and diastolic blood pressure of =90 mmHg. Other vital signs showing no clinically relevant deviations according to the Investigator’s judgment. 10.12-lead electrocardiogram (ECG) recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the Investigator. 11.Subject smokes =65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: 1.Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, or any uncontrolled condition that will affect bone metabolism such as, but not limited to: osteogenesis imperfecta, hyperparathyroidism, non-controlled hyperthyroidism (thyroid stimulating hormone(TSH)3 years cumulative use, and any dose within 12 months of Scr c.Parathyroid hormone or PTH derivatives(eg, teriparatide, abaloparatide), and selective estrogen receptor modulators(eg, raloxifene) within 1year of Scr d.Romozosumab within 30days prior to Scr e.Calcitonin within 6months of Scr f.Other bone metabolism drugs: administration of any of the following treatments within the last 3 months, i.anabolic steroids or testosterone ii.glucocorticoids(>5mg/day prednisone or equivalent for>10days) iii.systemic hormone replacement therapy iv.tibolone v.calcitriol vi.anticonvulsants(except benzodiazepines and pregabalin) vii.heparin viii.systemic use of ketoconazole, androgens, adrenocorticotropic hormone, cinacalcet or any cathepsin K inhib.(eg, odanacatib), aluminium, lithium, protease inhib., methotrexate, gonadotropin releasing hormone agonists 6.Osteonecrosis of the jaw or risk factors for ONJ such as invasive dental procedures(eg, tooth extraction, dental implants, oral surgery in the past 6months), periodontal, and/or pre-existing dental disease 7.Evidence of hypo/hypercalcemia at Scr defined as 10. mg/dL Note: If hypocalcaemia can be excluded based on calcium, corrected calcium, albumin, PTH, vitamin D3 values but ionized calcium is pending, the subject may be randomized, as per PI assessment and confirmation that exclusion criterion 7 has not been met. This needs to be recorded on source documents 8.Known vitamin D deficiency (25-hydroxy vitamin D level <20ng/mL[50nmol/L]) after supplementation at Screening 9.Known intolerance to Ca or vitamin D 10.Any current active infections, including localized infections, or any recent history(within 1 week prior to study drug administration) of active infections or a history of recurrent or chronic infections 11.Presence of known current infection with hepatitis B or presence of positive serology – ie, hepatitis B surface antigen(HBsAg) and/or hepatitis B core antibody(anti HBc)(hepatitis B core antigen test can be performed to conclude patient status), hepatitis C virus(HCV) antibody or human immunodeficiency virus(HIV) at Scr Note: Any subject with positive anti-HBc at Scr should be reviewed and evaluated by the PI to exclude active infection. It is at the PI’s discretion whether to extend diagnostics to exclude current infection of hepatitis B. A local HBV quantitative DNA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To demonstrate clinical similarity of AVT03 and United States-licensed Prolia® (US-Prolia, generic name: denosumab, hereafter referred to as Prolia) in terms of percent change from Baseline in bone mineral density (BMD) at 12 months •To demonstrate clinical similarity of AVT03 and Prolia in terms of area under the percent change from Baseline in serum C telopeptide of type 1 collagen up to 6 months (AUEC0 6months of %Cfb sCTX 1). Note: This objective will be considered as primary for European Medicines Agency (EMA) submission only; for all other agencies, this objective will be considered as secondary. ;Secondary Objective: •To further compare clinical similarity of AVT03 and Prolia •To assess and compare the safety of AVT03 with Prolia •To assess and compare immunogenicity of AVT03 with Prolia •To compare pharmacokinetic (PK) biosimilarity between AVT03 and Prolia •To compare pharmacodynamic (PD) parameters between AVT03 and Prolia ;Primary end point(s): Percent change from Baseline in LS BMD at 12 months Area under the percent change from Baseline in serum C-telopeptide of type 1 collagen up to 6 months (AUEC0 6months of %Cfb sCTX 1). Note: This endpoint will be considered as primary for EMA submission only; for all other agencies, this endpoint will be considered as secondary. ;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoint •Percent change from Baseline in LS BMD at 6 and 18 months •Percent change from Baseline in hip and femoral neck BMD at 6, 12, and 18 months •Incidence of new morphometric vertebral fractures at 12 and 18 months Pharmacodynamic endpoints •Percent change from Baseline in sCTX-1 at 3, 6, 9, 12, and 18 months Safety endpoints •Incidence, nature, and severity of adverse events including adverse drug reactions •Frequency and severity of injection site reactions •Frequency and severity of findings in routine safety parameters, including clinical laboratory assessments (hematology, clinical biochemistry, coagulation, urinalysis, and urine microscopy), vital signs, ECG, and physical examination Immunogenicity endpoint •Frequency and titer of anti-drug antibodies and frequency of neutralizing antibodies against AVT03 and Prolia at predose and Day 1, Day 2, Day 12, Day 30, Day 60, Day 90, Day 180, Day 270, Day 365 (Month 12), Day 365 (Month 12) +2 weeks, Month 15, and Month 18 (EoS) after treatment. Pharmacokinetic endpoint •Serum trough concentration of AVT03 and Prolia ;Timepoint(s) of evaluation of this end point: Efficacy endpoint - 6, 12 and 18 months. Pharmakodynamic endpoint - 3, 6, 9, 12 and 18 months. Immunogenicity endpoint - day 1, day 2, day 12, day 30, day 60, day 90, day 180, day 270, day 365, Day 365 (Month 12) +2 weeks, month 15, month 18. | — |
Countries
Bulgaria, Czechia, Czech Republic, Georgia, Poland, South Africa
Contacts
Public ContactSVP Clinical & Medical Affairs
Alvotech Swiss AG
Outcome results
None listed