CTRI/2024/05/067203 [Registered on: 10/05/2024] Trial Registered Prospectively
Last Modified On:
21/10/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
Comparative Pharmacokinetic Study of Dr. Reddy’s Vedolizumab Administered by the Intravenous Route to Normal Healthy Male Volunteers
Scientific Title of Study
A Single Dose, Double-Blind, Parallel Arm, Comparative Pharmacokinetic Study of Dr. Reddy’s Vedolizumab (DRL_VZ), US approved Reference Vedolizumab (Entyvio®) and EU approved Reference Vedolizumab (Entyvio®), Administered by the Intravenous Route to Normal Healthy Male Volunteers
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
VZ-01-001 v2.0 dated 09 February 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Hiren Prajapati
Designation
MD (Pharmacology)
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.
2nd, 3rd & 4th Floor, Shivalik Plaza-A,
Near I.I.M., Ambawadi, Ahmedabad – 380 015, India.
Ahmadabad GUJARAT 380015 India
Phone
7967773000
Fax
Email
Hiren.P1891@veedacr.com
Details of Contact Person Scientific Query
Name
Narendra Maharaj
Designation
Head - Clinical Development
Affiliation
Dr. Reddys Laboratories Ltd.
Address
Dr. Reddys Laboratories Ltd. Biologics
Survey Nos. 47 & 44 (Part), Bachupally Village, Bachupally Mandal,
Medchal Malkajgiri District,
Telangana, India - 500 090.
www.drreddys.com
Medchal TELANGANA 500 090 India
Phone
04044644000
Fax
04023041418
Email
narendramaharaj@drreddys.com
Details of Contact Person Public Query
Name
K Ranjith
Designation
Head - Outsourced Clinical Operations
Affiliation
Dr. Reddys Laboratories Ltd
Address
Dr. Reddys Laboratories Ltd. Biologics
Survey Nos. 47 & 44 (Part), Bachupally Village,
Bachupally Mandal,
Medchal Malkajgiri District,
Telangana, India - 500 090.
www.drreddys.com"
Medchal TELANGANA 500 090 India
Phone
4044644000
Fax
4023041418
Email
ranjithk@drreddys.com
Source of Monetary or Material Support
Dr. Reddys Laboratories Ltd. Biologics
Survey Nos. 47 & 44 (Part), Bachupally Village, Bachupally Mandal,
Medchal Malkajgiri District,
Telangana, India - 500 090.
www.drreddys.com
Primary Sponsor
Name
Dr. Reddys Laboratories Ltd.
Address
Dr. Reddys Laboratories Ltd. Biologics
Survey Nos. 47 & 44 (Part), Bachupally Village, Bachupally Mandal,
Medchal Malkajgiri District,
Telangana, India - 500 090.
www.drreddys.com"
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 1
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Hiren Prajapati
Veeda Clinical Research Limited, and Sterling Hospital
Veeda Clinical Research Ltd.
2nd, 3rd & 4th Floor, Shivalik Plaza-A, Near I.I.M., Ambawadi,
Ahmedabad – 380 015, India.
Phone: +91-79-6777 3000
And
Sterling Hospital
Sterling Hospital Rd,
Near Maharaja agrasen vidyalaya, L.K society, Nilmani Society,
Memnagar, Ahmedabad,
Gujarat 380052
Contact no. 07940011662
Ahmadabad GUJARAT
Single dose 300mg dose of DRL_VZ by intravenouse administration.
Dose: 300mg
Frequency: Single dose
Route of administration: Intravenous administration
Total duration: Intervention(Intervention/comparator) is given only once (single dose)
If total duration meant the duration of infusion, then it is over 30 minutes (+5 minutes window)
Comparator Agent
Entyvio® (EU-approved product)
Single dose of Entyvio® (EU- approved product) by intravenous administration
Dose: 300mg
Frequency: Single dose
Route of administration: Intravenous administration
Total duration: comparator is given only once (single dose)
If total duration meant the duration of infusion, then it is over 30 minutes (+5 minutes window)
Comparator Agent
Entyvio® (US-approved product)
Single dose of Entyvio® (US- approved product) by intravenous administration.
Dose: 300mg
Frequency: Single dose
Route of administration: Intravenous administration
Total duration: comparator is given only once (single dose)
If total duration meant the duration of infusion, then it is over 30 minutes (+5 minutes window)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
50.00 Year(s)
Gender
Male
Details
1. Healthy male volunteers, 18 to 50 years of age (both age inclusive), at the time of signing informed consent.
2. In general, good health as determined by a qualified physician based on a comprehensive medical history (including exclusion of progressive multifocal leukoencephalopathy [PML] by specific questioning on symptoms [Appendix III]), vital signs, physical examination, clinical laboratory tests and 12-lead ECG before randomization.
3. Body mass index between 18.5-30.0 kg/m2 (both inclusive) and body weight of 50.0 – 90.0 kg (both inclusive).
4. Screening parameters (vital signs, physical examination, clinical laboratory tests, 12-lead ECG) within the normal range or if outside the normal range then assessed as clinically non-significant by the Investigator (unless the value constitutes an explicit exclusion criterion).
5. Subjects must be willing to avoid sperm donation; and subjects or their female partner (if they are women of childbearing potential [WOCBP]) must be willing to use at least 1 highly effective method of contraception (as per Clinical Trials Facilitation and coordination Group (CTFG) guidelines (adopted and implemented on 21/09/2020))
6. Capable and amenable to providing written informed consent to the study requirements.
7. Willing to stay on study restrictions and contraception for 28 weeks and abide by the study processes till the end of the study (including follow-up period if applicable).
ExclusionCriteria
Details
1. Positive test result or 3 successive indeterminate test results for Quantiferon TB Gold test or positive test result for syphilis, hepatitis B, hepatitis C, or HIV 1/ 2 Virus at screening.
2. Live organism vaccination within 3m prior to randomization or any planned vaccination with live vaccines during the entire study. Non-live vaccines within 6 weeks prior to randomization or any planned vaccination with non-live vaccines during the entire study.
3. Any prior exposure to vedolizumab or to any other agent directly acting on integrin signalling including investigational products.
4. Subject with 1 or more positive responses for the PML symptoms mentioned in the PML Questionnaire at screening or randomization.
5. History of Immunodeficiency or other clinically significant immunological disorders, or auto-immune disorders.
6. Subject with ongoing or frequent/ recurring infection defined as more than 3 infection events per year requiring treatment or prior herpes zoster infection not fully healed including the post-herpetic neuralgia period if occurring within 1 year prior to randomization.
7. Clostridioides difficile infection within 3m, diarrhea lasting for more than 24h within 2m or any other intestinal infection within 1m prior to randomization.
8. History of allergic reaction or any adverse reaction following usage of Sodium Chloride Infusion.
9. History and or current presence of clinically significant in the opinion of the Investigator atopic allergy (e.g., asthma including childhood asthma, urticaria, angioedema, eczematous dermatitis), allergic reactions.
10. Allergy or hypersensitivity to any recombinant human or humanized antibodies, other therapeutic proteins or any excipients of at least one of the tested vedolizumab products or contraindication to the administration of IV fluid including 0.9% sodium chloride.
11. Blood donation, haemorrhage requiring treatment or transfusion, participation in any trial requiring blood sampling in the past 3m, plasma donation within the last 2 weeks or longer duration as per national regulation.
12. Screening or baseline blood pressure higher than 140mm Hg systolic or higher than 90 mm Hg diastolic BP, or volunteers currently on anti-hypertensive drugs.
Note: Up to 2 repeats in different days (on the same day are also allowed if white coat hypertension is suspected) are allowed and, in this case, the mean of the measurements will be used to decide on eligibility. Blood pressure is to be measured on the same arm in the sitting position after 5minutes rest.
13. History of (in the opinion of the investigator) difficulty in obtaining peripheral IV access, history of orthostatic or postural hypotension, fainting spells, or blackouts, history of difficulties with blood sampling - situations that potentially may interfere with the study objectives, as per the opinion of the Investigator.
14. QTc longer than 450 milliseconds or other clinically relevant ECG abnormalities such as atrial fibrillation, atrial flutter, Wolf-Parkinson-White syndrome, presence of a cardiac pacemaker or any other electrocardiographic abnormality considered clinically relevant by the Investigator.
15. History or presence of any clinically relevant nervous system disease including, but not restricted to any stroke/ transient ischaemic attack or seizures other than febrile seizures before the age of 5 years
16. History and/or current presence of gastrointestinal, renal, endocrine, pulmonary including chronic obstructive pulmonary disease, hepatic, cardiovascular (including history of or presence of angina, exertional dyspnea, orthopnea, congestive heart failure or myocardial infarction and thrombotic or embolic episode requiring treatment), haematological (including pancytopenia, aplastic anaemia or blood dyscrasia and coagulopathies), neurological, psychiatric, genitourinary, metabolic (including known diabetes mellitus) disorder or condition. This criterion includes any disorder or condition that, in the investigators opinion, may interfere with the safety of the subject, the study evaluations or the subject compliance to the study procedures.
17. Impaired hepatic function (alanine transaminase / aspartate transaminase value greater than 1.5 times the upper limit of the reference range and/or serum bilirubin greater than 1.25 times the upper limit of the reference range at the screening visit). Ensure total protein and albumin levels are within the acceptable range as per Principal Investigator judgement. For abnormal ALT or AST values below 1.5 times the upper limit of normal (ULN) or serum bilirubin below 1.25 times the ULN, the subject can be included upon investigators clinical judgement. If a laboratory error or a quickly reversible intercurrent event is suspected, up to 2 repeats are allowed. Subjects who have documented evidence of presence of Gilberts disease may be included in the study if they have total bilirubin of less than 3 mg/dL (or less than 51.3micromol/L) with indirect bilirubin contributing to greater than 80 percent of the total bilirubin as per the laboratory test.
18. Acute infection including coronavirus disease of 2019 (COVID-19) ongoing, at the time of screening or randomization., or chronic infections including systemic fungal infection in the last 6m.
19. Participation in an interventional study in the last 3m, currently is on follow-up visit schedule for any study, participation in more than 3 studies of experimental drug products in the past 12m, intake of an investigational drug in another trial within 6m or 5t1/2, whichever is longer prior to administration of IP in this trial or longer duration as per national regulation. Those subjects who are in the long term extension phase for collection of immunogenicity sample will also be excluded.
20. Intake of any medication including herbal products within 3 weeks prior to dosing. Exceptions to this rule are:
a. Paracetamol at doses up to 4 grams per day and ibuprofen at doses up to 1200 mg per day as well as nonabsorbable antacids and topical heparinoids in non-occlusive application are allowed at any time.
b. Multivitamins not containing lipid soluble vitamins at supraphysiological doses are allowed at any time if considered as not potentially clinically relevant or interfering by the Investigator.
c. Topical non-steroidal anti-inflammatory drugs are allowed until 72h before dosing and from 72h after dosing onwards.
d. Medications which require longer washout:
10 weeks: Bismuth salts, digitoxin, fluoxetine, flurazepam, medazepam, mephenytoin, mephobarbital, phenprocoumone, phenylbutazone, pimozide, pirimethamine, phenobarbital, primidone, protryptiline, teicoplanin. 18 weeks: flunarizine, mefloquine, trimethadione. 26 weeks: gold salts, immunoglobulins (antitetanus and antirabies post-exposure prophylaxis allowed until 3 weeks predose) or antibodies (monoclonal or not), systemic retinoids, chloroquine, hydroxychloroquine, and amiodarone.
21. History of any cancer, including carcinoma in situ, lymphoma or leukaemia.
22. Major surgery within the past 6m, or any surgery including dental interventions planned during entire study period.
23. Current smokers or those who gave up smoking less than 3m, prior to screening, tobacco chewer or those who gave up tobacco chewing less than 3m prior to screening, or positive in the urine cotinine test at screening or at check-in or admission to clinical facility.
24. Positive test for ethanol as per the clinical facility standard at screening or at check-in to clinical facility.
25. History or current positive test for drugs of abuse (benzodiazepine, amphetamines, barbiturates, cocaine, methadone, phencyclidine,3,4methylenedioxymethamphetamine, tetrahydrocannabinol, and opiates) in urine at screening or at check-in to clinical facility.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Pharmacokinetic parameters (calculated by standard non compartmental methods on actual sampling times): AUC (0-∞)
Samples for PK analysis will be obtained throughout the study (from predose till Day 169).
Secondary Outcome
Outcome
TimePoints
• Pharmacokinetic parameters: AUC(0-t), AUC0-71d [main partial AUC], AUC0-57d and AUC0-85d [supportive partial AUCs], Cmax, tmax, apparent terminal decline rate constant λz (also known as apparent terminal elimination rate constant kel), t1/2, CL, Vss and Vz; %AUCext will be reported to evaluate the coverage of AUC by the sampling schedule but is not considered a PK endpoint. • Safety and tolerability of all treatments as assessed by vital signs, adverse events (AEs), physical examination, injection site reaction inspection, electrocardiogram (ECG), clinical laboratory safety data.
• Comparative incidence, (and if present, titer and neutralizing capacity) of anti-vedolizumab antibodies.
Samples for PK analysis will be obtained throughout the study (from predose till Day 169).
Samples for immunogenicity assessment will be collected throughout the study (from pre-dose till Day 169).
Target Sample Size
Total Sample Size="132" Sample Size from India="132" Final Enrollment numbers achieved (Total)= "132" Final Enrollment numbers achieved (India)="132"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 1 comparative study conducted by Dr. Reddy’s Laboratories Ltd in male volunteers with US approved Reference Vedolizumab (Entyvio®) and EU approved Reference Vedolizumab (Entyvio®) to compare the Pharmacokinetic parameters. Dr.Reddy’s Vedolizumab (company product code: DRL_VZ) is being developed as a biosimilar to the US approved Reference Vedolizumab (Entyvio®) and EU approved Reference Vedolizumab (Entyvio®) as a part of global development program. Normal healthy volunteers (NHV) are the population of choice (unless precluded for safety reasons) to establish PK similarity. The current study will be performed only in male subjects to avert gender-related variability. The 300mg IV singledose is known to be safe for administration to NHV as it has been tested withappropriate safety and tolerability in prior studies.