Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000520639
Ethics application status
Approved
Date submitted
24/04/2023
Date registered
19/05/2023
Date last updated
11/01/2024
Date data sharing statement initially provided
19/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Compare the Pharmacokinetic, Pharmacodynamics, safety, Tolerability and Immunogenicity of BP16 versus Prolia (US and EU approved) in Healthy male Volunteers.
Scientific title
A Randomized, Double-Blind, Parallel group, Comparative Phase I study for the assessment of Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of BP16 versus US licensed - Prolia® and EU approved - Prolia® Following a Single dose (60mg/mL) Subcutaneous Administration in Healthy Male Volunteers
Secondary ID [1] 309057 0
BP16-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 329115 0
Condition category
Condition code
Musculoskeletal 326089 326089 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participant will be randomly assigned to one of three arms in a 1:1:1 ratio to receive single dose (60mg/mL) of either BP16 or EU-Prolia® (EU sourced Denosumab) or US-Prolia® (US sourced Denosumab)

Any information related to the participant is recorded across the source documentation and signed off by the appropriate staff member who performs specific inpatient duties and protocol-required tasks. The source records the time and the staff member who performed the duties for audit purposes.
Intervention code [1] 325498 0
Treatment: Drugs
Comparator / control treatment
EU - Prolia® (EU sourced Denosumab)

Both US and EU Prolia are reference comparators
Control group
Active

Outcomes
Primary outcome [1] 333954 0
Pharmacokinetic assessment will be done by AUC (0-inf), Cmax, AUC (0-t), % AUC ext, Tmax, T (1/2), first-order terminal elimination rate constant, Apparent systemic clearance (CL/F) and Apparent volume of distribution (Vd/F).
Yes Blood samples will be collected to assess the Pk, PD and Immunogenicity
Timepoint [1] 333954 0
Scheduled time points as per protocol PK blood samples will be collected at pre-dose (collected within 1 h prior to the study drug administration) and post dose, 1h (± 5mins), 4h (±5mins), 8h (±10mins), 12h
(±30mins), 24h (±1h), 48h (±2h), 72h (±4h), 96h (±4h), Day 6 (120h±4h), Day 8+1
(168h+24h), Day 10+1 (216h+24h), Day 12+1 (264h+24h), Day 14+1(312+24h) Day
16+1(360+24h), Day 22±1 (504h±24h), Day 29±1 (672h±24h), Day 43±2 (1008h±48h),
Day 57±2 (1344h±48h), Day 71±3 (1680h±72h), Day 85±3, Day 99±3, Day 113±3, Day
141±3, Day 169±3. Day 197±3.and Day 253±3
Primary outcome [2] 334042 0
Pharmacodynamic assessment will be done by quantification of Serum type 1 C-telopeptide (CTX1) levels

Timepoint [2] 334042 0
PD blood samples will be collected at Pre-dose (collected prior to study drug administration
on day 1) and, 24h (±1h), 48h (±2 h), 72h (±4h), 96h (±4h), Day 6 (120h±4h), Day 10+1
(216h+24h), Day 22±1 (504h±24h), Day 29±1 (672h±24h), Day 43±2 (1008h±48h), Day 57±2 (1344h±48h), Day 71±3 (1680h±72h), Day 85±3, Day 99±3, Day 113±3, Day 141±3, Day
169±3 Day 197±3, Day 225±3 and Day 253±3
Primary outcome [3] 334045 0
Safety Assessment will be done by clinical Safety Laboratory Assessments (measuring Hematology assessment, Clinical Chemistry, Coagulation Profile, Urinalysis and Urinalysis), electrocardiograms and injection site reaction
Timepoint [3] 334045 0
Planned time points for all safety assessments are provided in the schedule of events

Haematology, clinical chemistry, calcium, Vit D and ECG assessment will be performed on screening, day -1, day 3 (48h±2h), day 8, day 29 and EOS visit (day 253±3). Additional time points for calcium assessment is on post dose – day 1, 8h , day 57, day 85, day 113, day 169 and EOS visit (day 253±3). Additional time points for Vit D assessment is on post dose – day 57, day 85, day 113 and day 169 and EOS visit (day 253±3). Vital signs will be checked at Predose , post dosing at 30 mins, 2 hours , and 6 hours , on Day 1 and 24h , 48h , 72h , 96h , at each ambulatory visit , at the EOS (day 253±3) and whenever required as per the discretion of Investigator
Secondary outcome [1] 418826 0
Incidence and titer of Anti-drug antibody (ADAs) to Denosumab..
Timepoint [1] 418826 0
Samples should be collected before the SC injection of the study drug. The exact date and time of sample collection must be recorded in the source documentation and the eCRF. A detailed process for immunogenicity sampling, handling, storage, and shipping will be provided in the laboratory manual for PK, PD and immunogenicity.

Blood samples for ADA will be collected at Pre-dose (collected within 1h prior to study drug administration) on Day 1, and Post-dose at, Day 14±1, Day 29±1, Day 57±2, Day 85±3, Day 141±3, Day 197±3 and 253±3.
Secondary outcome [2] 421914 0
Incidence of Neutralizing antibody (NAb's) in all the Anti-drug antibody (ADA)-positive subjects.
Timepoint [2] 421914 0
Blood samples for ADA will be collected at Pre-dose (collected within 1h prior to study drug administration) on Day 1, and Post-dose at, Day 14+1, Day 29±1, Day 57±2, Day 85±3, Day 141±3, Day 197±3 and 253±3.

Eligibility
Key inclusion criteria
Each subject must meet all of the following criteria to be randomized in the study.

1.Male healthy volunteers of age 28-55 years (Inclusive of both) at the time of signing informed consent.

2.Body weight of 60 to 100 kg (both inclusive) and BMI of 18.5 to 30 kg/m2 (both inclusive) at screening visit and day -1 visit.

3.Subjects must understand the nature, purpose of the study including possible risks and side effects, agreed to participate in the study and is willing to sign the informed consent form before any study specific procedures.

4.Subjects are able to understand and comply with protocol requirements and instructions.

5.Subjects with no clinically relevant abnormalities detected during baseline history, physical examination and vital signs (blood pressure, pulse rate, body temperature, including respiratory rate) as judged by the Investigator at screening and day -1 visit.

6.Non-smokers or casual smokers who smoke no more than 5 cigarettes (or equivalent quantity of any other nicotine containing substance) per week. Subject must abstain from smoking 48 hours prior to day -1.
Minimum age
28 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1.Known history or presence of hypersensitivity to the active substance (Denosumab) or to any of the other excipients of investigational products.

2.History of cardiovascular, hepatic, ophthalmic, pulmonary, neurological, metabolic, hematological, gastrointestinal, endocrine, immunological, psychiatric or any other disease which in the opinion of the Investigator would make the subject inappropriate for study participation.

3.Abnormal and clinically relevant (in the opinion of the Investigator) vital signs, ECG, history of angina, exertional dyspnea, orthopnea, congestive heart failure, or myocardial infarction.

4.Have a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus, or human immunodeficiency virus (HIV) I and II at screening.

5.History of and/or current illness within 28 days prior to the study drug administration that is identified as clinically significant by the investigator.

6.Major surgery or major trauma within past six months of screening or anticipated need for any surgery during the study duration.

7.History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 21 units of alcohol per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).

8.Subject with evidence of a condition (psychological, emotional problems, any disorders or resultant therapy) that is likely to invalidate informed consent or limit the ability of the subject to comply with the protocol requirements in the opinion of the investigator.

9.Subjects with positive drug test at screening or admission.

10.Blood donation within 90 days or platelet/plasma donation within 14 days prior to dosing and during the study.

11.Difficulty in blood sampling or difficulty in accessibility of veins.

13.A serious infection (associated with housing and/or required intravenous anti-infectives) within 6 months before study drug administration and/or any active infection within 4 weeks of screening requiring oral or systemic antibiotics.

14.Subject is not likely to complete the study for whatever reason in the opinion of the investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
The statistical considerations summarized in this section outline the plan for data analysis in this study. Details of the statistical analyses, methods, and data conventions to be conducted will be specified in a statistical analysis plan (SAP),

Pharmacokinetic Analysis

Primary PK Endpoints

The log-transformed pharmacokinetic parameters (AUC0-inf, AUC0-t and Cmax) will be analyzed using ANCOVA model.

Secondary PK Analysis

Secondary PK parameters will be summarized by-treatment using n, mean, SD, %CV, minimum, median, maximum, geometric mean, and geometric %CV.

Pharmacodynamic Analyses

The PD parameters will be summarized by-treatment using n, mean, SD, %CV, minimum, median, maximum, geometric mean, and geometric %CV.

Immunogenicity Analyses

The immunogenicity assessments will be summarized for the safety population. The number and percentage of subjects who develop anti-Denosumab antibodies will be presented.

Safety Analysese

Clinical safety will be evaluated by assessing adverse events, injection site reactions, laboratory assessments, physical examination, 12-lead ECG and vital signs results in a descriptive manner.


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/06/2023
Actual
26/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
204
Accrual to date
78
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 24588 0
Nucleus Network - Melbourne
Recruitment hospital [2] 24593 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 40183 0
3004 - Melbourne
Recruitment postcode(s) [2] 40188 0
4006 - Herston
Recruitment outside Australia
Country [1] 26071 0
New Zealand
State/province [1] 26071 0
Auckland

Funding & Sponsors
Funding source category [1] 313261 0
Commercial sector/Industry
Name [1] 313261 0
CuraTeQ Biologics Private Ltd.
Country [1] 313261 0
India
Primary sponsor type
Commercial sector/Industry
Name
CuraTeQ Biologics Private Ltd.
Address
Galaxy, Floors: 22-24, Plot No. 1, Survey No. 83/1,
Hyderabad Knowledge City, Raidurg Panmaktha,
Rangareddy Dist., Hyderabad,
Telangana, India, 500 081
Country
India
Secondary sponsor category [1] 315064 0
Commercial sector/Industry
Name [1] 315064 0
PPD Australia Pty. Ltd.
Address [1] 315064 0
412 St Kilda Road, Melbourne VIC 3004
Country: Australia
Country [1] 315064 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312492 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 312492 0
The Alfred Hospital Ethics Committee
The Alfred Hospital Ethics Committee ,55 Commerical Rd, Melbourne VIC 3004
Ethics committee country [1] 312492 0
Australia
Date submitted for ethics approval [1] 312492 0
06/04/2023
Approval date [1] 312492 0
13/04/2023
Ethics approval number [1] 312492 0
HREC/91633Alfred-2022
Ethics committee name [2] 314454 0
Northern A Health and Disability Ethics Committee
Ethics committee address [2] 314454 0
Ministry of Health
133 Molesworth Street,
PO Box 5013
Wellington
6011
Ethics committee country [2] 314454 0
New Zealand
Date submitted for ethics approval [2] 314454 0
28/09/2023
Approval date [2] 314454 0
16/11/2023
Ethics approval number [2] 314454 0
2023 FULL 18838

Summary
Brief summary
A Randomized, Double-Blind, Parallel group, Comparative Phase I study for the assessment of Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of BP16 versus US licensed - Prolia® and EU approved - Prolia® Following a Single dose (60mg/mL) Subcutaneous Administration in Healthy Male Volunteers

This is a phase 1 , multi centre randomized double blinded clinical trial in healthy male volunteers Primary objective is to assess the Pharmacokinetic similarity and to establish the Bioequivalence between the BP16 versus US licensed - Prolia® and EU approved - Prolia® Following a Single dose (60mg/mL) Subcutaneous Administration in Healthy Male Volunteers
Secondary objective is to assess the Pharmacodynamic similarity , to monitor the safety ,tolerability and to assess the immunogenicity between the BP16 versus US licensed - Prolia® and EU approved - Prolia® Following a Single dose (60mg/mL) Subcutaneous Administration in Healthy Male Volunteers
204 Subjects will be enrolled and randomized in 1:1:1 ratio to receive the single dose subcutaneous injection of BP16/EU Prolia /US Prolia .


Trial website
Trial related presentations / publications
Public notes
We have added 2 new sites in New Zealand,

a. PCRN
PCRN Trials Limited, trading as PCRN Auckland
Level 2, 2 Fred Thomas Drive, Takapuna, Auckland, 0622, New Zealand

b. NZCR
New Zealand Clinical Research OPCO Ltd
Ground Floor 3, Ferncroft Street, Grafton, Auckland, 1010, New Zealand

Contacts
Principal investigator
Name 124854 0
Dr Sam Francis
Address 124854 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Rd,
Melbourne 3004

Address: Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Rd,
Melbourne 3004, VIC
Country 124854 0
Australia
Phone 124854 0
+61 0466640801
Fax 124854 0
Email 124854 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 124855 0
Dr Paul Hamilton
Address 124855 0
PCRN Trials Limited, trading as PCRN Auckland
Level 2, 2 Fred Thomas Drive, Takapuna, Auckland, 0622, New Zealand
Country 124855 0
New Zealand
Phone 124855 0
+64 22 585 0357
Fax 124855 0
Email 124855 0
paulhamilton@pcrn.co.nz
Contact person for scientific queries
Name 124856 0
Dr Arpitkumar Prajapati
Address 124856 0
CuraTeQ Biologics Private Ltd,
Plot No. 1, Survey No. 83/1, Hyderabad Knowledge City,
Raidurg Panmaktha, Rangareddy Dist.,
Hyderabad 500081, Telangana
Country 124856 0
India
Phone 124856 0
+91 8455255222
Fax 124856 0
Email 124856 0
Arpitkumar.Prajapati@curateqbio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18474Ethical approval    385449-(Uploaded-21-04-2023-16-09-00)-Study-related document.pdf
21362Ethical approval    385449-(Uploaded-16-11-2023-16-11-09)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.