CTRI/2024/03/063701 [Registered on: 06/03/2024] Trial Registered Prospectively
Last Modified On:
22/08/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of Cladribine 10 mg tablet in relapsing forms of multiple sclerosis patients
Scientific Title of Study
A Prospective, Randomized, Open Label, Balanced, Single Dose, Two Stage, Two-Treatment, Two-Period, Two-Sequence, Crossover Bioequivalence Study of Cladribine Tablet (Intas
Pharmaceuticals Ltd.) Compared with Mavenclad® (EMD Serono, Inc.) in Patients with Relapsing
Forms of Multiple Sclerosis.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
iVRS-CD-23-069_Version 01, Dated 29 Dec 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pande Amitkumar Vardhaman
Designation
MBBS, MD(Medicine), DM Neurology
Affiliation
Medipoint Hospitals Pvt. Ltd.,
Address
Medipoint Hospitals Pvt. Ltd., Room number 01, 1st floor, Department of Neurology, OPD
Building, 241/1, New D.P. Road, Aundh,
Pune MAHARASHTRA 411007 India
Phone
9860918000
Fax
2027298081
Email
dramitkumarpande.pentagon@gmail.com
Details of Contact Person Scientific Query
Name
Dr Channabasavanna G Halasagi
Designation
Medical Monitor
Affiliation
Invitro Research Solutions Pvt. Ltd.,
Address
Invitro Research Solutions Pvt. Ltd., Clinical Development Department, Medical Monitoring Division, Room No 301, 3rd Floor, No. 22 & 23, Kodigehalli Main Road, Sahakar Nagar Post, Hebbal,
Bangalore KARNATAKA 560092 India
Phone
6366947473
Fax
Email
channa@ivrs.org.in
Details of Contact Person Public Query
Name
T Vijaya Bhaskar
Designation
Director Clinical Development
Affiliation
Invitro Research Solutions Pvt. Ltd.,
Address
Invitro Research Solutions Pvt. Ltd, Clinical Development
Department, Clinical Operations Division, 2nd Floor No. 22 & 23, Kodigehalli Main Road, Sahakar Nagar Post, Hebbal,
Bangalore KARNATAKA 560092 India
Phone
6366575282
Fax
Email
vijay@ivrs.org.in
Source of Monetary or Material Support
Intas Pharmaceuticals Limited,
Corporate House, Near Sola Bridge, S.G. Highway, Thaltej, Ahmedabad – 380054, Gujarat, India.
Department of Neurology, Room No. 02, Ground Floor, OPD Building, City Neurology Centre, Behind Gautam Upvan, Maqbool Alam Road, Khajuri, Varanasi-221002 Varanasi UTTAR PRADESH
7753936002
drzafar4@gmail.com
Dr Bashir Ahmad Sanaie
Government Medical College
Department of Neurology, Room No. 02, Ground Floor, OPD Building, Shireen Bagh, Srinagar, Jammu And Kashmir - 190010, India Srinagar JAMMU & KASHMIR
9419063190
drb_ahmad@yahoo.com
Dr Pande Amitkumar Vardhaman
Medipoint Hospitals Pvt. Ltd.,
Department of Neurology, Room number 01, Ground floor, OPD
Building, Medipoint Hospitals Pvt. Ltd., 241/1, New
D.P. Road, Aundh,
Pune – 411007,
Maharashtra, India Pune MAHARASHTRA
Department of Neurology, Room number 01, Ground floor, OPD Building, Punjagutta, Hyderabad, Telangana - 500082 India Hyderabad TELANGANA
9246589899
surmukh99@gmail.com
Dr Janardhan D C
Rajalakshmi Hospital and Research Center
Department of Neurology, 3rd Floor, OPD Building, Rajalakshmi Hospital and Research Center, 21/1, Lakshmi Pura, Main Road, Opp. Lakshmipura Lake, Vidyaranyapura Post, Bangalore Bengaluru (Bangalore) Urban Karnataka - 560097 India Bangalore KARNATAKA
9986046906
dcjanardhan@yahoo.com
Dr Rahul Dhoot
Saideep Healthcare and Research Pvt Ltd
Room No. 4, Floor No.1, OPD Building, Saideep Healthcare and research Pvt Ltd,
Viraj Estate, Yashwant Colony, Near DSP Chowk, Ahmednagar-414003 Ahmadnagar MAHARASHTRA
8007010808
rahulrdhoot@yahoo.co.uk
Dr Rajesh B Iyer
Sparsh Super Speciality Hospital
ROOM NO.02,2ND FLOOR, Sparsh Super Speciality Hospital.#146, Infantry Road, Opposite to Police commissioner s office, Banglore, Karnataka,
India-560001 Bangalore KARNATAKA
Manufactured by: Intas
Pharmaceuticals Limited India
The recommended cumulative dosage of cladribine tablet is 3.5 mg per kg body
weight administered orally and divided into 2 yearly treatment courses (1.75 mg per
kg per treatment course). Each treatment course is divided into 2 treatment cycles: Each cycle lasting 4 to 5 consecutive days. Do not administer more
than 20 mg/day.
Comparator Agent
MAVENCLAD® (Cladribine) tablets
10 mg
Manufactured for: : EMD Serono, Inc., Rockland, MA 02370.
The recommended cumulative dosage of cladribine tablet is 3.5 mg per kg body weight administered orally and divided into 2 yearly treatment courses (1.75 mg per kg per treatment course). Each treatment course is divided into 2 treatment cycles: Each cycle lasting 4 to 5 consecutive days. Do not administer more than 20 mg/day.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1 Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study and in this protocol and is willing to participate in the study.
2 Man or woman participant must be greater than or equal to 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), at the time of signing the informed consent.
3 Body weight greater than or equal to 40 Kg
4 Participants with relapsing forms of multiple sclerosis including relapsing-remitting disease and active secondary progressive disease as per McDonald’s criteria, who are eligible and planned
to receive for the first cycle of either first or second treatment course of oral cladribine tablet as per investigator judgement.
NOTE: If a participant is receiving their Second Course/First Cycle of oral cladribine under
current study, then it must be at least 43 weeks after the last dose of First Course/Second Cycle.
5 A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP)
OR
a. Is a WOCBP and agrees to remain on an acceptable contraceptive method that is highly
effective (with a failure rate of less than 1% per year), with low user dependency when used
consistently and correctly
b. during the intervention phase and for at least 6 months after the last dose of study
intervention and agrees not to donate eggs (ova, oocytes) for the purpose of
reproduction during the study and for a period of at least 6 months after the last dose
of study intervention. The investigator should evaluate the effectiveness and the
potential for contraceptive method failure (e.g., noncompliance, recently initiated) of
the contraceptive method in relationship to the first dose of study intervention.
c. A WOCBP must have a negative highly sensitive serum pregnancy test at screening
and urine pregnancy test before each dosing.
d. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum
pregnancy test is required. In such cases, the participant must be excluded from
participation if the serum pregnancy result is positive
The investigator is responsible for review of medical history, menstrual history, and recent
sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
6 Male participants are eligible to participate if they agree to the following during the intervention phase and for at least 6 months after the last dose of study intervention:
a. Must agree not to donate sperm for the purpose of reproduction
PLUS EITHER:
b. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent
on a long-term and persistent basis) and agree to remain abstinent
OR
a. Must agree to use contraception /barrier as detailed below
b. A male participant must wear a condom when engaging in any activity that allows for
passage of ejaculate to another person.
c. Male participants should also be advised of the benefit for a female partner to use a
highly effective method of contraception as condom may break or leak when having
sexual intercourse with a woman of childbearing potential who is not currently
pregnant
7 Participant with adequate hematologic, and renal function at screening visit
a. Absolute lymphocyte count between 1000-4000 cells/microliter before initiating the first treatment course OR greater than 800 cells/microliter before initiating the second treatment course at screening visit.
b. Estimated creatinine clearance Greater than or equal to 60 mL/min as estimated by the Cockcroft-Gault formula
8 Willing and able to adhere to the lifestyle restrictions specified in this protocol.
9 Participants who are seronegative to VZV must be vaccinated with varicella vaccine (live or live attenuated) prior to initiation of study intervention. If participant has received varicella vaccine (live or live attenuated) in the past or seropositive to VZV at screening, they must agree to be vaccinated with recombinant, adjuvanted vaccine during screening phase and throughout the study period if applicable.
Participants must have completed vaccinations and immunizations including most current
COVID 19 vaccination according to the local immunization guidelines prior to administration
of the study intervention. Investigators must review and confirm vaccinations and
immunizations status. Participants may be rescreened in case of any pending vaccination(s).
ExclusionCriteria
Details
1 Documented medical history of uncontrolled, clinically significant intercurrent cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
2 Known allergies, hypersensitivity, or intolerance to any of the study interventions, or components/excipients thereof (refer to the US prescribing information of Mavenclad), or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
3 Contraindications to the use of study intervention per latest US prescribing information of Mavenclad
4 Current unstable liver or biliary disease with Child-Pugh score less than 6 at screening visit.
5 Participant with clinically significant current cardiac conditions like serious cardiac arrhythmia not controlled by adequate medication, electrocardiographic evidence of acute ischemic abnormalities, or any other cardiac illness that could lead to a safety risk to the participant in the opinion of the investigator.
6 Positive for HIV, or positive Hepatitis C antibody test or Hepatitis B surface antigen test and/or core antibody test for IgG and/or IgM.
7 Evidence of active or latent tuberculosis (TB) as detected by local standard of practice such as imaging and/or positive QuantiFERON-TB Gold test.
8 Presence of any clinically significant active systemic bacterial, viral or fungal infections (acute or chronic) as assessed by investigator at randomization. Randomization can be delayed till resolution or control of infection as assessed by investigator allowing use of cladribine tablet.
9 Live or live-attenuated vaccine(s) within 6 weeks prior to randomization, or plans to receive such vaccines during the study. Participants must agree to avoid live or live-attenuated vaccine(s) after study till white blood cell counts are within normal limits.
10 Current evidence or history of malignancy within the past 3 years except for (a) basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of disease for 3 years; or (b) any malignancy which is considered cured with minimal risk of recurrence AND whose natural history or treatment does not have the potential as judged by the investigator to interfere with the safety of the study intervention are eligible for this study.
11 Participants with neurological findings consistent with progressive multifocal leukoencephalopathy (PML), or confirmed PML. Baseline MRI is required during screening period if not done in past 3 months prior to administration of study intervention if it is the participant’s first treatment course.
12 Received a study intervention or used an invasive investigational medical device within 30 days or 5 half-lives prior to randomization, whichever is longer.
13 Participant’s clinical condition would not be feasible for pharmacokinetic assessment as determined by investigator.
14 Unable to swallow solid, oral dosage forms whole with the aid of water (participants must not chew, divide, dissolve, or crush the study intervention)
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Following primary pharmacokinetic parameters
will be assessed:
a. Cmax and AUC0-t
After First Dose
Secondary Outcome
Outcome
TimePoints
Following secondary pharmacokinetic
parameters will be assessed:
a. AUC0-∞, Tmax, AUC_% Exp, R2
adjusted, λz,
t1/2
After First Dose
Frequency and/or incidence of adverse
events (AE) and Serious Adverse Events
(SAE)
For entire study
Target Sample Size
Total Sample Size="30" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "30" Final Enrollment numbers achieved (India)="30"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is a Prospective, Randomized, Open Label, Balanced, Single Dose, Two Stage, Two Treatment, Two-Period, Two-Sequence, Crossover Bioequivalence Study of Cladribine Tablet (Intas
Pharmaceuticals Ltd.) Compared with Mavenclad® (EMD Serono, Inc.) in Patients with Relapsing
Forms of Multiple Sclerosis. This study will be conducted in 2 phases: a 21 day
screening phase, approximate 2-3 months of intervention phase extending from Day 1 (baseline) barring
the delay if any as allowed by the protocol. The duration of individual participation will be approximately
111 days. These are estimated approximate duration calculated based on ideal scenario. Additional safety
follow-up visit(s) may be required at monthly interval till month 6 from Day 1 only if the absolute
lymphocyte count at EOS visit is below 200 cells/microliter to monitor and record. Each participant will receive study intervention on the Day 1 of each cycle within
one treatment course. Participant will be taking Mavenclad on Day 2 to 4/5 (based on individual patient’s
dose requirement) of each cycle in the study at home. Sponsor will provide participants with the
prescribed reference product. Primary Endpoint is Cmax and AUC0-t, Secondary Endpoint is AUC0-∞, Tmax, AUC_% Exp, R2
adjusted, λz,
t1/2 Safety endpoint of the study is Frequency and/or incidence of adverse
events (AE) and Serious Adverse Events
(SAE).