Clinical trial NCT05395091: Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND
Official title: A Randomized, Double-Blind, Parallel Design, Repeat Dose, 2-arm, Multicenter Study Comparing the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profiles of AVT03 and US-Prolia® in Postmenopausal Women With Osteoporosis, ALVOBOND
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis, Postmenopausal
Keywords: Postmenopausal Osteoporosis, Denosumab, Alvotech
Lead sponsor: Alvotech Swiss AG
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 532
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, parallel design, repeat dose, 2 arm, multicenter study comparing the efficacy, safety, immunogenicity, pharmacodynamic (PD) and pharmacokinetic (PK) profiles of AVT03 and US-Prolia in postmenopausal women with osteoporosis.

Detailed description: After the screening activities, eligible subjects were randomized to receive either AVT03 60 mg or Prolia® 60 mg, administered as a subcutaneous (s.c.) injection on Day 1 and at Month 6. At Month 12, subjects in AVT03 treatment group will received a third dose of AVT03 60 mg administered s.c. while subjects in Prolia® treatment group will were be re-randomized 1:1 to receive either Prolia 60 mg or AVT03 60 mg administered as a subcutaneous injection.

Afterwards, the subjects will be followed until the End of Study (EoS) Visit.

Eligibility criteria: 1. Postmenopausal women with osteoporosis willing to sign an informed consent form (ICF)and able to undergo protocol related procedures.
2. A baseline dual-energy x-ray absorptiometry (DXA) scan with a T score ≤-2.5 and

   * 4.0 at the LS (L1 to L4)and/or, total hip, and/or femoral neck.
3. Age: ≥50 years.
4. Female subject is postmenopausal according to 1 of the following criteria:

   1. Spontaneous amenorrhea for ≥12 consecutive months
   2. Biochemical criteria of menopause, follicle-stimulating hormone, \>40 IU/L except surgically sterile
   3. Having had bilateral oophorectomy ≥6 weeks prior to Screening
5. Willing to receive calcium plus vitamin D supplements.
6. At least 2 consecutive evaluable lumbar vertebrae and at least 1 evaluable hip.

Exclusion Criteria

1. Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, or any uncontrolled condition that will affect bone metabolism
2. History and/or presence of 1 severe or more than 1 moderate vertebral fractures confirmed by x-ray.
3. History of hip fracture
4. Presence of active healing fractures
5. Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures
6. Evidence of hypo/hypercalcemia at Screening
7. Known vitamin D deficiency
8. Known intolerance to calcium and vitamin D supplement.

Primary outcomes:
measure: Percent Change From Baseline in LS BMD at Month 12 to Demonstrate Comparable Efficacy of AVT03 and Prolia®.
timeFrame: Baseline to Month 12
measure: To Demonstrate Comparable Profile of AVT03 and Prolia in Terms of Area Under the Percent Change From Baseline in Serum C-telopeptide of Type 1 Collagen (AUEC of %Cfb sCTX-1)
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: Percent Change From Baseline in LS BMD
timeFrame: Month 6, Month18
measure: Percent Change From Baseline in Hip and Femoral Neck BMD
timeFrame: Month 6, Month 12, Month 18
measure: Incidence of New Morphometric Vertebral Fractures
timeFrame: Month 12 and 18
measure: Percent Change From Baseline in sCTX-1
timeFrame: Month 3, Month 6, Month 9, Month 12 and Month 18
measure: Incidence, Nature and Severity of Adverse Events Including Adverse Drug Reactions
timeFrame: Month 18
measure: Frequency and Severity of Injection Site Reactions
timeFrame: Month 12
measure: Frequency and Severity of Findings in Routine Safety Parameters
timeFrame: Month 18
measure: Frequency and Titer of Anti-drug Antibodies and Frequency of Neutralizing Antibodies Against AVT03 and Prolia
timeFrame: Month 18
measure: Serum Trough Concentration of AVT03 and Prolia
timeFrame: Month 18
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Investigational Site 3501
city: Plovdiv
country: Bulgaria
facility: Investigational Site 3503
city: Stara Zagora
country: Bulgaria
facility: Investigational Site 3502
city: Praha
country: Czechia
facility: Investigational Site 4201
city: Uherské Hradiště
country: Czechia
facility: Investigational Site 4202
city: Tbilisi
country: Georgia
facility: Investigational Site 9901
city: Tbilisi
country: Georgia
facility: Investigational Site 9902
city: Tbilisi
country: Georgia
facility: Investigational Site 9903
city: Tbilisi
country: Georgia
facility: Investigational Site 9904
city: Tbilisi
country: Georgia
facility: Investigational Site 9905
city: Tbilisi
country: Georgia
facility: Investigational Site 9906
city: Białystok
country: Poland
facility: Investigational Site 4803
city: Białystok
country: Poland
facility: Investigational Site 4804
city: Kraków
country: Poland
facility: Investigational Site 4802
city: Kraków
country: Poland
facility: Investigational Site 4807
city: Lublin
country: Poland
facility: Investigational Site 4811
city: Poznań
country: Poland
facility: Investigational Site 4812
city: Skierniewice
country: Poland
facility: Investigational Site 4801
city: Warsaw
country: Poland
facility: Investigational Site 4809
city: Zamość
country: Poland
facility: Investigational Site 4810
city: Łódź
country: Poland
facility: Investigational Site 4806
city: Świdnik
country: Poland
facility: Investigational Site 4805
city: Bloemfontein
country: South Africa
facility: Investigational Site 2705
city: Cape Town
country: South Africa
facility: Investigational Site 2714
city: Centurion
country: South Africa
facility: Investigational Site 2707
city: Centurion
country: South Africa
facility: Investigational Site 2708
city: Groenkloof
country: South Africa
facility: Investigational Site 2710
city: Johannesburg
country: South Africa
facility: Investigational Site 2712
city: Kwadukuza
country: South Africa
facility: Investigational Site 2702
city: Parow
country: South Africa
facility: Investigational Site 2711
city: Port Elizabeth
country: South Africa
facility: Investigational Site 2701
city: Pretoria
country: South Africa
facility: Investigational Site 2706
city: Pretoria
country: South Africa
facility: Investigational Site 2713
city: Worcester
country: South Africa
facility: Investigational Site 2703
Study officials:
affiliation: Alvotech Swiss AG
name: Felicitas Bullo
role: STUDY_DIRECTOR
References: