This is a randomized, double-blind study to
demonstrate similar efficacy and safety of TVB-009P compared to PROLIA US over 78 weeks
administered sc at doses of 60 mg every 26 weeks (3 injections) in patients with PMO.
This study will consist of 3 periods:
screening period of up to 4 weeks
double-blind main treatment period of 52 weeks
double-blind transition period of 26 weeks
After informed consent is obtained, eligibility criteria will be reviewed and screening evaluations
will be performed.
At baseline, patients will be randomized in a 1:1 ratio to receive the first 2 doses of TVB-009P or
PROLIA US (“main treatment period”). The first dose of TVB-009P or PROLIA US will be
administered following randomization. The second dose will be administered 26 weeks after the
first dose.
Criteria:
The patient provides a signed and dated written informed consent.
b. The patient is a clinically stable, ambulatory, female postmenopausal adult (≥60 and
≤90 years) with a diagnosis of osteoporosis.
c. The patient is of postmenopausal status, defined as:
Spontaneous amenorrhea for >12 months, or
Spontaneous amenorrhea >6 months and serum follicle stimulating hormone
(FSH) and estradiol (E2) in menopausal range, or
Surgical menopause at least 6 weeks before the start of screening.
d. The patient has a body weight ≥50 kg and ≤90 kg (≥110 lb and ≤198 lb) at screening.
e. The patient agrees to be supplemented with 1000 mg calcium and at least 400 IU
vitamin D daily from screening until the last visit.
f. The patient has a bone mineral density (BMD)-measurement T-score of less than -2.5
but not less than -4.0 by dual energy X-ray absorptiometry (DXA) at the lumbar spine
at screening based on central reader assessment.
g. The patient has at least 3 (three) vertebrae in the L1-L4 region that are evaluable by
DXA.
h. The patient has serum 25 (OH) vitamin D level >20 ng/mL at screening and no
current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside
the normal range, as assessed by the central laboratory. Vitamin D and calcium
supplements will be provided and patients may be rescreened once to re-evaluate
calcium and/or vitamin D level post repletion.
i. The patient must be willing and able to comply with study restrictions and to remain
at the investigational center for the required duration during the study period, and
willing to return to the investigational center for further visits, as applicable, and the
follow-up procedures and assessments as specified in this protocol.
Exclusion Criteria: Patients will be excluded from participating in this study if they meet any of
the following criteria:
a. The patient has a known malabsorption of calcium or vitamin D supplements.
b. The patient has a metabolic or bone disease (except osteoporosis) such as Paget’s
disease, Cushing’s disease, rheumatoid arthritis, sclerosteosis, osteomalacia,
osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, hyperprolactinemia,
malabsorption syndrome, osteomyelitis, multiple myeloma or related
lymphoproliferative disorder, or bone metastases.
c. The patient has a current, uncontrolled hyperthyroidism or hypothyroidism, per
patient report or chart review.
d. The patient has hypoparathyroidism or hyperparathyroidism (irrespective of current
controlled or uncontrolled status).
e. The patient has a history and/or presence of risk factors of osteonecrosis of the jaw, as
determined by the principal investigator, (eg, unhealed open soft tissue lesions in the
mouth, poor oral hygiene, periodontal disease, poorly fitting dentures, history of
dental disease, recent or planned invasive dental procedures such as tooth extractions
within the next 18 months), presence of anemia or coagulopathy at screening, and/or
inability to maintain oral hygiene during the study.
f. The patient has a history and/or presence of 1 severe or more than 2 moderate
vertebral fractures (as determined by central reading of lateral spine X-ray during the
screening period).
g. The patient has a history and/or presence of hip fracture or atypical femur fracture.
h. The patient has participated in another study of an IMP (or a medical device) within
the previous 30 days or 5 half-lives of the IMP (whichever is longer) or longer if
required by local regulations, or is currently participating in another study of an IMP
(or a medical device).
i. The patient has a known hypersensitivity to any components of the IMPs stated in this
protocol or to calcium or vitamin D.
j. The patient has a renal impairment manifested with an estimated glomerular filtration
rate (eGFR) <45 mL/min.
k. The patient has cardiac disease as per investigator's discretion, including
electrocardiogram (ECG) abnormalities at screening indicating significant risk of
safety for patients participating in the study.
l. The patient has a malignancy or past malignancy (except for local non-melanoma
skin cancer fully resected).
m. The patient has a current skin infection(s).
n. The patient has infectious disease:
Acute infection and/or antibiotic treatment must be resolved 28 days prior to the
first dose of IMP.
Any relevant chronic infection.
Ongoing hepatitis B, hepatitis C, human immunodeficiency virus (HIV) Types 1
or 2 infection.
Positive test for coronavirus disease 2019 (COVID-19) during screening or
patient reporting a recent history of confirmed COVID-19 which had not fully
recovered more than 14 days before screening.
o. The patient has any medical condition that (treated or untreated), in the opinion of the
investigator, could jeopardize or would compromise the patient’s safety or ability to
participate in this study.
p. The patient has had any prior treatment with denosumab (PROLIA or XGEVA or
biosimilars of denosumab products).
q. The patient has used intravenous bisphosphonates within less than 5 years prior to
screening.
r. The patient has used oral bisphosphonates within the 12 months prior to start of
screening and/or cumulative use >3 years before the start of screening.
Efficacy/Safety Study–Postmenopausal Osteoporosis
s. The patient has ongoing use of any osteoporosis treatment (other than calcium and
vitamin D supplements). The following rules for prior use of osteoporosis treatments
have to be adhered to:
Drugs being investigated for osteoporosis, eg romosozumab: dose received at any
time.
Strontium or fluoride (for osteoporosis): dose received at any time.
Teriparatide or any parathyroid hormone (PTH) analogs: dose received within
12 months before the start of screening.
Calcitonin: dose received within 6 months before the start of screening.
Cinacalcet: dose received within 3 months before the start of screening.
t. The patient has ongoing use of any bone active drugs which can affect BMD
including:
Heparin (except topical), anti-convulsives (with the exception of
benzodiazepines), systemic ketoconazole, adrenocorticotropic hormone, lithium,
gonadotropin releasing hormone agonists, or anabolic steroids; dose received
within 3 months before the start of screening.
Systemic glucocorticosteroids: total cumulative dose of ≥50 mg within 3 months
prior to randomization.
Systemic oral or transdermal estrogen or selective estrogen receptor modulators:
more than 1 month of cumulative use within 6 months prior to randomization.
u. The patient is a pregnant or lactating woman, or plans to become pregnant during the
study.
v. The patient has a history of chronic alcohol or drug abuse within the previous
6 months.
w. The patient is vulnerable (eg, people kept in detention).