CTRI/2024/02/063265 [Registered on: 28/02/2024] Trial Registered Prospectively
Last Modified On:
18/11/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
This is a randomized, double-blind, two-arm, single-dose, parallel-group study in normal healthy adult male volunteers.
Scientific Title of Study
A Randomized, Double-blind, Two-arm, Single-dose, Parallel Group Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Bmab 1000 and EU-approved Xgeva® in Normal Healthy Male Volunteers
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
BIO-BMl000-103, Ver 2.0 dated 08-Dec-2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Ankitkumar Ranpura
Designation
SENIOR DIRECTOR
Affiliation
Biocon Biologics Limited
Address
Biocon Biologics Limited, Biocon House, Semicon Park, Electronics City, Phase - II Bengaluru (India) - 560100
Biocon Biologic Limited, Electronic City, Bangalore 560100
Bangalore KARNATAKA 560100 India
Phone
08028082808
Fax
Email
ankitkumar.ranpura@biocon.com
Details of Contact Person Public Query
Name
Rajesh CN
Designation
Senior Director
Affiliation
Biocon Biologic Limited
Address
Biocon Biologic Limited, Electronic City, Bangalore 560100
Bangalore KARNATAKA 560100 India
Phone
08028082808
Fax
Email
rajesh.cn@biocon.com
Source of Monetary or Material Support
Biocon Biologics UK Limited
6, Great Queen Street, Covent Garden,
London, WC2B 5AH, United Kingdom
Primary Sponsor
Name
Biocon Biologics UK Limited
Address
6, Great Queen Street, Covent Garden
London, WC2B 5AH,United Kingdom
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Biocon Biologics Limited
Biocon House, Semicon Park, Electronics City, Phase - II Bengaluru (India) - 560100
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Shrikrishna Kolte
Lambda Therapeutic Research Ltd.,
Lambda House, Plot No. 38, Survey No. 388,
Near Silver Oak Club, S. G. Highway, Gota, Ahmedabad - 382481, Gujarat, India.
Ahmadabad GUJARAT
079-40202020
shrikrishnakotle@lambda-cro.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Riddhi Medical Nursing Home, Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Normal Healthy Volunteer
Intervention / Comparator Agent
Type
Name
Details
Intervention
Bmab 1000
single dose of 35 mg subcutaneous injection.
Comparator Agent
EU-approved Xgeva
Single dose of 35 mg subcutaneous injection.
Inclusion Criteria
Age From
28.00 Year(s)
Age To
55.00 Year(s)
Gender
Male
Details
1. Gender: Male
2. Age: 28-55 years, both inclusive, at screening
3. Weight: 50.0-95.0 kg, both inclusive, at screening
4. Body mass index between 18.0 kg/m2 and 30.0 kg/m2, both inclusive, at screening
5. Willingness to participate in the 9-month study and follow all study-related procedures/restrictions by signing or providing thumb impression on the written informed consent form
6. Resting supine systolic blood pressure (SBP) of <140/>90 mmHg and diastolic blood pressure of <90/>60 mmHg. Other vital signs showing no clinically relevant deviations in the Principal Investigator’s (PI’s) judgment.
7. 12-lead ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the PI
8. Ability and willingness to abstain from alcohol from 48 hrs prior to drug administration and 48 hrs prior to ambulatory visits, and during the stays in the clinical research center until discharge from the in-house period
9. Fertile males participating in heterosexual relations: willingness to use adequate contraception (i.e., two effective methods, one of which must be a physical barrier method) from screening until 36 weeks after dosing or must be sexually inactive by abstinence, which is consistent with the preferred and usual lifestyle of the subject.
Note: Effective forms of contraception are a condom, an established form of hormonal contraception, a diaphragm or cervical/vault cap, or an intrauterine device. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Sterile men, and subjects who have same-sex sexual relations, do not have to use contraception
10. White blood cells, platelet count, hemoglobin, other hematology, and biochemistry tests of blood and urine within the reference ranges of the safety laboratory. Minor deviations considered to lack any clinical relevance by the PI can be accepted.
ExclusionCriteria
Details
1. Any past or concurrent medical conditions potentially increasing the subject’s risks during participation in the study. Examples of these include medical history with evidence of clinically relevant pathology (e.g., malignancies, demyelinating disorders)
2. Unable to follow protocol instructions in the opinion of the PI
3. History of relevant drug and/or food allergies (including hypersensitivity to any recombinant protein drug, latex, or any of the constituents of Bmab 1000/Xgeva)
4. Known history of exposure to denosumab (even in trial setting)
5. Prior diagnosis of bone disease, or any condition that will affect bone metabolism such as, but not limited to, osteoporosis, osteogenesis imperfecta, hyperparathyroidism, hyperthyroidism, hypothyroidism, osteomalacia, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, current flare-up of osteoarthritis and/or gout, active malignancy, renal disease (defined as glomerular filtration rate <60 mL/min), Paget’s disease of the bone, recent bone fracture (within 6 months), malabsorption syndrome
6. Any prior use of bone-modifying medications. This includes medications such as, but not limited to, bisphosphonates, fluoride, calcitonin, strontium, parathyroid hormone or derivatives, anabolic steroids, calcitriol, diuretics, over the counter medications, herbal supplements within the last 3 months before screening
7. Use of systemic glucocorticosteroids (≥5 mg prednisone equivalent per day for ≥10 days) within the past 3 months before screening. Topical and nasal corticosteroids will be allowed
8. Any current active infections, including localized infections, or any recent history of active infections, cough, or fever, or a history of recurrent or chronic infections that require systemic antibiotic therapy (within 1 week prior to study drug administration)
9. Treatment with non-topical medications (including over the counter medication and herbal remedies such as St. John’s Wort extract) within 7 days prior to study drug administration, with the exception of topical medications, multivitamins, Vitamin C, Vitamin D, calcium, food supplements, and a limited amount of acetaminophen, which can be used throughout the study
10. Personal/family history suggestive of prolonged QT interval syndrome or family history of sudden death
11. Having received live vaccines during the 4 weeks prior to study drug administration or has the intention to receive live vaccination during the study
12. Have previously been exposed to a monoclonal antibody or fusion protein (other than denosumab) within 270 days (or five half-lives, whichever is the longest) prior to randomization and/or there is clinical suspicion or confirmed evidence of immunogenicity from previous exposure to a monoclonal antibody or fusion protein
13. Have previously been exposed to an immunosuppressive agent or biological agent (other than a monoclonal antibody or fusion protein) within 120 days (or five half-lives, whichever is the longest) prior to randomization, except COVID-19 vaccine
14. 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 judged by the PI
15. Participant having Vitamin D total deficiency
16. Current hypocalcemia (albumin-adjusted serum calcium less than lower limits of normal reference range), history of allergy to Vitamin D or calcium supplements, intolerant to long-term calcium or Vitamin D supplementation, or malabsorption of calcium or Vitamin D supplements
17. Participation in a drug study within 90 days or five half-lives of the previous drug (if known), whichever is longer, prior to drug administration
18. Donation of blood (1 unit or 350 mL) within a period of 90 days prior to study drug administration
19. A recent history of harmful use of alcohol (<2 years), i.e., alcohol consumption of >14 standard drinks per week (a standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40% distilled spirits, such as rum, whisky, brandy, etc.) or consumption of alcohol or alcoholic products within 48 hrs prior to receiving study drug
20. Us
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
On-site computer system
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Cmax, maximum observed denosumab concentration
AUC0-t, area under the curve from 0 h to the last measurable concentration calculated by the linear-log trapezoidal method
• AUC0-∞, area under the curve from 0 h to infinity
0-253 day
Secondary Outcome
Outcome
TimePoints
CL/F, apparent clearance.
0-253 days
kel, elimination rate constan
0-253 days
t1/2, half-life
0-253 days
Vd/F, apparent volume of distribution
0-253 days
Tmax, time to reach Cmax
0-253 days
Target Sample Size
Total Sample Size="220" Sample Size from India="220" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is aimed to
determine the PK and PD comparability, safety, and tolerability of Bmab 1000
versus Xgeva (denosumab) in healthy, adult male volunteers for demonstrating
biosimilarity in accordance with the Japanese Pharmaceuticals and Medical
Devices Agency (PMDA), United States Food and Drug Administration (FDA),
European Medicines Agency (EMA), and New Drugs and Clinical Trials Rules, 2019
of the CDSCO (Central Drugs Standard Control Organization) guidance documents.
Bmab 1000 is being
developed as a proposed biosimilar to Xgeva. This study is aimed to determine
the PK and PD comparability, safety, and tolerability of Bmab 1000 versus Xgeva
(denosumab) in healthy, adult male volunteers for demonstrating biosimilarity
in accordance with the PMDA, US FDA, EMA, and CDSCO guidance documents. This
will be a single-dose, bioequivalence study following subcutaneous injection in
normal healthy male subjects.