| CTRI Number |
CTRI/2010/091/000254 [Registered on: 09/09/2010] |
| Last Modified On: |
05/03/2013 |
| Post Graduate Thesis |
|
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Efficacy and Safety of Daclizumab High Yield Process Versus Interferon β 1a in Patients With Relapsing-Remitting Multiple Sclerosis
|
|
Scientific Title of Study
|
Multicenter, Double-blind, Randomized, Parallel-group, Monotherapy, Active-control Study to Determine the Efficacy and Safety of Daclizumab High Yield Process (DAC HYP) versus Avonex® (Interferon β 1a) in Patients with Relapsing-Remitting Multiple Sclerosis |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2009-012500-11 |
EudraCT |
| 205-MS-301 |
Protocol Number |
| NCT01064401 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Shilpi Ray |
| Designation |
|
| Affiliation |
|
| Address |
Biogen Idec Biotech India Pvt. Ltd.
Vatika Towers, B Block, 14th Floor, Sec 54, Golf Course Sector Road,
Gurgaon
HARYANA
122001
India |
| Phone |
+91-124-4572300 |
| Fax |
+91-124-4572333 |
| Email |
shilpi.ray@biogenidec.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr. Anjali Nagpal |
| Designation |
|
| Affiliation |
Senior Advisor, Scientific Affairs |
| Address |
Biogen Idec Biotech India Pvt. Ltd
Vatika Towers, B Block, 14th Floor, Sec 54, Golf Course Sector Road,
Gurgaon
HARYANA
Haryana
India |
| Phone |
+91-124-4572300 |
| Fax |
+91-124-4572333 |
| Email |
anjali.nagpal@biogenidec.com |
|
Details of Contact Person
Public Query
|
| Name |
Shilpi Ray |
| Designation |
|
| Affiliation |
|
| Address |
Biogen Idec Biotech India Pvt. Ltd.
Vatika Towers, B Block, 14th Floor, Sec 54, Golf Course Sector Road,
Gurgaon
HARYANA
122001
India |
| Phone |
+91-124-4572300 |
| Fax |
+91-124-4572333 |
| Email |
shilpi.ray@biogenidec.com |
|
|
Source of Monetary or Material Support
|
| Biogen Idec Innovation House 70 Norden Road Maidenhead Berkshire SL4 6AY, United Kingdom |
|
Primary Sponsor
Modification(s)
|
| Name |
Biogen Idec Inc |
| Address |
14 Cambridge Center
Cambridge, MA 02142
USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. Sanjay Ramteke |
Jasleen Hospital |
Opp Big Bazaar,Pnachsheel Square-440012
Nagpur
MAHARASHTRA |
+917122458303
ssrt95@yahoo.co.in |
| Dr. R Srinivasa |
MS Ramiah Hospital |
New B E L Road, ,M S Ramaiah Nagar, MSRIT Post,-560 054
Bangalore
KARNATAKA |
080-22183126
drrsrinivasa@hotmail.com |
| Dr. Neeta Mehta |
Neeta Mehta Clinic, |
D-502, 5th Floor, Rizvi Nagar, Milan Subway Junction, S.V. Road,,-400054
Mumbai
MAHARASHTRA |
drneetamehta@gmail.com |
| Dr. P. Satish Chandra |
NIMHANS Department of Neurosciences |
,-
|
|
| Dr. AK Meena |
Nizams Institute of Medical Sciences |
Punjagutta,-500082
Hyderabad
ANDHRA PRADESH |
040-66461365
040-66461365
akmeena@hotmail.com |
| Dr. Roop Gursahani |
PD Hinduja National Hospital and Medical Research Center |
V.S. Marg,Mahim-400016
Mumbai
MAHARASHTRA |
|
| Dr. Muralidharan Nair |
Sree Chitra Tirunal Institute of Medical Science and Technology |
Ganga Bhavan,General Post Office Lane-695011
|
0471-2524450
nairmuralidharan@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| Central India Medical Research Ethics Committee |
Approved |
| Independant Ethics Committee |
Approved |
| Institutional Ethics Committee |
Approved |
| MSRMC Ethical Review Board |
Approved |
| NIMHANS Ethics Committee |
Approved |
| P.D Hinduja National Hospital & Medical Research Centre, Clinical Research Ethics Committee |
Approved |
| Sree Chitra Tirunal Institute of Medical Science and Technology Institutional Ethics Committee |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Relapsing Remitting Multiple Sclerosis, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
Avonex (IFN β-1a) |
30 mcg intramuscular (IM) injection once weekly for 96 to 144 weeks |
| Intervention |
Daclizumab High Yield Process (DAC HYP) |
150 mg sub-cutenous (SC) once every 4 weeks for 96 to 144 weeks |
|
|
Inclusion Criteria
|
| Age From |
|
| Age To |
|
| Gender |
|
| Details |
Inclusion Criteria
To be eligible for this study, candidates must meet the following
eligibility criteria prior to randomization or at the timepoint specified in
the individual criteria listed below:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Must be 18 to 55 years of age, inclusive, at the time of consent.
3. Must have a confirmed diagnosis of RRMS according to McDonald
criteria, numbers 1 through 4 (Polman et al, 2005), and a cranial
MRI demonstrating lesion(s) consistent with MS (it is not necessary to obtain a current scan if a scan performed previously is available; if a previous scan is not available, then the baseline scan may be used).
4. Must have a baseline EDSS between 0.0 and 5.0, inclusive.
5. Must meet one of the following disease activity-related criteria:
a) Two or more clinical relapses within the previous 3 years with
at least 1 clinical relapse in the 12 months prior to
randomization.
OR
b) One or more clinical relapses and 1 or more new MRI lesions
(Gd+ and/or T2 hyperintense lesion) within the previous 2 years
with at least one of these events in the 12 months prior to
randomization. The new MRI lesion must be distinct from one
associated with the clinical relapse. The baseline MRI may be
used to satisfy this criterion.
Note: For inclusion purposes, a clinical relapse is defined as neurologic
signs and/or symptoms documented in the medical record of at least 24
hours duration that are determined by the Investigator or the Treating
Neurologist as consistent with an MS relapse. Time since relapse should be
measured from the time of relapse onset. When inclusion is based on a new
MRI lesion, activity must be verified by the central MRI reading center.
6. Male subjects and female subjects of childbearing potential must be
willing to practice effective contraception during the study and be
willing and able to continue contraception for 4 months after their
last dose of study treatment. |
|
| ExclusionCriteria |
| Details |
Exclusion Criteria
Candidates will be excluded from study entry if any of the following
exclusion criteria exist at randomization or at the timepoint specified in the
individual criteria listed below:
Medical History
1. Diagnosis of primary progressive, secondary progressive, or
progressive relapsing MS (as defined by Lublin and Reingold,
2001). These conditions require the presence of continuous clinical
disease worsening over a period of at least 3 months. Patients with
these conditions may also have superimposed relapses, but are
distinguished from relapsing remitting patients by the lack of
clinically stable periods or clinical improvement.
2. Known intolerance, contraindication to, or history of non-compliance with Avonex 30 mcg.
Note: Current or prior use of an approved IFN β preparation for MS,
including Avonex, is allowed as long as the subject is currently appropriate
for Avonex treatment according to local prescribing information.
3. History of malignancy; however, subjects with a history of excised
or treated basal cell carcinoma or fewer than 3 squamous cell
carcinomas are eligible to participate in this study.
4. History of severe allergic or anaphylactic reactions.
5. Known hypersensitivity to study drugs or their excipients.
6. History of abnormal laboratory results that, in the opinion of the
Investigator, are indicative of any significant cardiac, endocrine,
hematological, hepatic, immunologic, metabolic, urologic,
pulmonary, gastrointestinal, dermatologic, psychiatric, renal,
neurological (other than MS), and/or other major disease that would
preclude administration of DAC HYP or Avonex.
7. History of human immunodeficiency virus (HIV) or other
immunodeficient conditions.
8. History of drug or alcohol abuse (as defined by the Investigator)
within the 2 years prior to randomization.
9. History of seizure disorder or unexplained blackouts OR history of
a seizure within 6 months prior to Baseline.
10. History of suicidal ideation or an episode of clinically severe
depression (as determined by the Investigator) within 3 months
prior to Day 1. Subjects receiving ongoing antidepressant therapy
will not be excluded from the study unless the medication has been
increased within the 6 months prior to Baseline.
11. An MS relapse that has occurred within the 50 days prior to
randomization AND/OR the subject has not stabilized from a
previous relapse prior to randomization.
12. Known history of, or positive screening test result for hepatitis C
virus or hepatitis B virus.
13. Varicella or herpes zoster virus infection or any severe viral
infection within 6 weeks before screening.
14. Exposure to varicella zoster virus within 21 days before screening.
15. Any of the following abnormal blood tests at screening:
? hemoglobin ≤9.0 g/dL
? platelets ≤100 x 109/L
? lymphocytes ≤1.0 x 109/L
? neutrophils ≤1.5 x 109/L
? alanine aminotransferase/serum glutamate pyruvate
transaminase (ALT/SGPT), aspartate aminotransferase/serum
glutamic oxaloacetic transaminase (AST/SGOT), or
gamma-glutamyl-transferase ≥2 times the upper limit of normal
(ULN)
? serum creatinine ≥ULN
Treatment History
16. Any previous treatment with daclizumab or other anti-CD25
monoclonal antibody.
17. Any type of live virus vaccine from 4 weeks before randomization,
including but not limited to, measles/mumps/rubella vaccine,
varicella zoster virus vaccine, oral polio vaccine, and nasal
influenza vaccine.
18. Infection (viral, fungal, bacterial) requiring hospitalization or
intravenous (IV) antibiotics within 8 weeks before randomization.
19. Elective surgery performed from 2 weeks prior to randomization or
scheduled through the end of the study.
20. Treatment with another investigational drug or approved therapy for
investigational use within the 6 months prior to randomization.
21. Prior treatment with the any of the following:
? total lymphoid irradiation
? cladribine
? T cell or T cell receptor vaccination
? any therapeutic monoclonal antibody, except natalizumab
22. Prior treatment with mitoxantrone, cyclophosphamide, fingolimod,
or natalizumab within 1 year prior to randomization.
23. Prior treatment with any of the following medications or procedures
within the 6 months prior to randomization:
? cyclosporine
? azathioprine
? methotrexate
? mycophenolate mofetil
? intravenous immunoglobulin
? plasmapheresis or cytapheresis.
24. Treatment with any of the following medications within the 30 days
prior to randomization:
? IV corticosteroid treatment
? oral corticosteroid treatment
? glatiramer acetate
Note: Subjects who are currently receiving an approved IFN β preparation
are not required to washout from IFN β prior to randomization, but IFN β
treatment must be discontinued prior to randomization.
25. Initiation of treatment or dose adjustment of commercially-available
Fampridine-SR within the last 90 days.
Note: Subjects who have been on a stable dose of commercially-available
Fampridine-SR for longer than 90 days are not excluded. Use of
compounded or other formulations of 4-aminiopyridine is excluded.
Miscellaneous
26. Female subjects who are currently pregnant or breastfeeding.
27. Female subjects considering becoming pregnant while in the study.
28. Previous participation in this study.
29. Subjects for whom MRI is contraindicated, i.e., have pacemakers or
other contraindicated implanted metal devices, are allergic to
gadolinium, or have claustrophobia that cannot be medically
managed.
30. Unwillingness or inability to comply with the requirements of the
protocol, including the presence of any condition (physical, mental,
or social) that is likely to affect the subject?s ability to comply with
the protocol.
31. Other medical reasons that, in the opinion of the Investigator and/or
Biogen Idec, make the subject unsuitable for enrollment. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Annualized relapse rate (ARR) |
96 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| The secondary endpoints (rank ordered) for this study are:
1) Number of new or newly-enlarging T2 hyperintense lesions on brain MRI over 96 weeks
2) Change in Multiple Sclerosis Functional Composite (MSFC) score
3) Sustained disability progression defined by at least a 1.0-point increase on EDSS from baseline EDSS ≥1.0 that is sustained for 12 weeks or at least a 1.5-point increase on the EDSS from baseline EDSS <1.0 that is sustained for 12 weeks
4) Change in Multiple Sclerosis Impact Scale 29 (MSIS-29) physical score
5) The proportion of subjects who are relapse-free |
96 weeks |
|
Target Sample Size
Modification(s)
|
Total Sample Size="1500"
Sample Size from India="50"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
Date Missing |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
30/09/2010 |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This is a multicentric global trial with a sample size of 1500 patients
The primary study objective is to test the superiority of DAC HYP compared to IFN-b-1a in preventing MS relapse in subjects with RRMS. We have obtained approval to recruit upto 50 patients in India and the anticipated date to start recruitment in India is as on 30-Sep-2010.
|