| CTRI Number |
CTRI/2022/09/045929 [Registered on: 27/09/2022] Trial Registered Prospectively |
| Last Modified On: |
06/12/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants with Duchenne Muscular Dystrophy (DMD) |
|
Scientific Title of Study
|
A Double-Blind, Placebo-Controlled, Multicenter Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy |
| Trial Acronym |
ESSENCE |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 4045-301, Version 12 (Amendment 11) dated 14/May/2021 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
|
| Phone |
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| Fax |
|
| Email |
|
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Details of Contact Person
Scientific Query
|
| Name |
Rashmi Chitgupi |
| Designation |
Country Head - Clinical Management |
| Affiliation |
PPD Pharmaceutical development India Private Limited |
| Address |
PPD Pharmaceutical development Pvt ltd India
101, A Wing, Fulcrum, Hiranandani Business Park
PPD Pharmaceutical development Pvt ltd India
101, A Wing, Fulcrum, Hiranandani Business Park
Mumbai
MAHARASHTRA
400099
India |
| Phone |
912266022900 |
| Fax |
|
| Email |
rashmi.chitgupi@ppd.com |
|
Details of Contact Person
Public Query
|
| Name |
Rashmi Chitgupi |
| Designation |
Country Head - Clinical Management |
| Affiliation |
PPD Pharmaceutical development India Private Limited |
| Address |
PPD Pharmaceutical development Pvt ltd India
101, A Wing, Fulcrum, Hiranandani Business Park
PPD Pharmaceutical development Pvt ltd India
101, A Wing, Fulcrum, Hiranandani Business Park
Mumbai
MAHARASHTRA
400099
India |
| Phone |
02266022900 |
| Fax |
|
| Email |
rashmi.chitgupti@ppd.com |
|
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Source of Monetary or Material Support
|
| Sarepta Therapeutics Inc
215 First Street Cambridge,
MA 02142 USA |
|
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Primary Sponsor
|
| Name |
Sarepta Therapeutics Inc |
| Address |
215 First Street Cambridge, MA 02142 USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
| Name |
Address |
| Sarepta Therapeutics Inc |
215 First Street
Cambridge, MA 02142 USA |
|
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Countries of Recruitment
|
Argentina
Belgium
Bulgaria
Canada
Czech Republic
Denmark
France
Germany
Greece
Hungary
India
Ireland
Israel
Italy
Mexico
Poland
Russian Federation
Serbia
Spain
Sweden
Taiwan
United Kingdom
United States of America
Australia
Republic of Korea |
|
Sites of Study
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Shefali Gulati |
All India Institute of Medical Sciences |
Dept of Paediatrics Neurology, Teaching Block, 3rd Floor, Room # 3056, Ansari Nagar, New-Delhi - 110029, India
New Delhi
DELHI
New Delhi
DELHI |
919810386847
sheffaligulati@gmail.com |
| Dr Ann Agnes Mathew |
Aster RV Hospital |
4th Floor, Department of Paediatrics, CA, #37, 24th main road, ITI Layout, 1st Phase, J.P Nagar, Bengaluru, Karnataka -560078, India
Bangalore
KARNATAKA
Bangalore
KARNATAKA |
919008360858
annagnesmathew@yahoo.co.in |
| Dr Sangeetha Yoganathan |
Christian Medical College |
Pediatric Neurology Unit, 1st Floor, Room number 14, West Block, IDA Scudder Rd, Vellore, Tamil Nadu 632004, India
Vellore
TAMIL NADU
Vellore
TAMIL NADU |
919442611622
doc_ys@yahoo.co.in |
| Dr Umesh Kalane |
Deenanath Mangeshkar Hospital and Research Centre |
Room No 18, Neuro Research Department, 2nd Floor New Building, Deenanath Mangeshkar Hospital Road, Near Mhatre Bridge, Erandwane, Pune, Maharashtra-411004, India
Pune
MAHARASHTRA
Pune
MAHARASHTRA |
919324316759
umeshkalane@yahoo.com |
| Dr Siddharth Shah |
Royal Institute of Child NeuroSciences |
Clinical Research Department, Basement Area, 2, Sumanglam Society, Drive In Rd, Thaltej, Ahmedabad, Gujarat 380054, India
Ahmadabad
GUJARAT
Ahmadabad
GUJARAT |
919909960555
sidh909@hotmail.com |
|
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Details of Ethics Committee
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Aster CMI Hospital Institutional Ethics Committee |
Approved |
| Institute Ethics Committee All India Institute of Medical Sciences |
Submittted/Under Review |
| Institutional Ethics Committee Deenanath Mangeshkar Hospital And Research Centre |
Submittted/Under Review |
| Institutional Review Board (IRB),Christian Medical College |
Submittted/Under Review |
| Sangini Hospital Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: G710||Muscular dystrophy, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo Comparator: Placebo followed by SRP-4045 or SRP-4053 |
Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study). |
| Intervention |
SRP-4045
Drug: SRP-4045
SRP-4045 solution for IV infusion
Other Names:Casimersen
AMONDYS 45 |
Participants amenable to exon 45 skipping will receive SRP-4045 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study). |
| Intervention |
SRP-4053
Drug: SRP-4053
SRP-4053 solution for IV infusion
Other Names:
Golodirsen
VYONDYS 53 |
Participants amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
|
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Inclusion Criteria
|
| Age From |
6.00 Day(s) |
| Age To |
13.00 Day(s) |
| Gender |
Male |
| Details |
1. Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
2. Stable dose of oral corticosteroids for at least 24 weeks prior to Week 1, and the dose is expected to remain constant throughout the study
(except for modifications to accommodate changes in weight).
3. Intact right and left biceps or 2 alternative upper muscle groups
4. Mean 6MWT ≥300 meters and ≤450 meters
5. Stable pulmonary function: forced vital capacity (FVC) ≥50% predicted |
|
| ExclusionCriteria |
| Details |
1.Treatment with gene therapy at any time
2. Previous treatment with SMT C1100 within 1 week prior to Week 1 and previous treatment with PRO045 (BMN 045), PRO053 (BMN 053), or PRO051 (BMN 051) within 24 weeks prior to Week 1
3. Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1
4. Major surgery within 3 months prior to Week 1
5. Presence of other clinically significant illness
6. Other inclusion/exclusion criteria may apply. |
|
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Method of Generating Random Sequence
|
Stratified randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Participant and Investigator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
| The primary objective of this study is to evaluate the effect of SRP-4045 and SRP-4053 (combined-active group) compared with placebo on ambulation, endurance, and muscle function as measured by the 6-minute walk test (6MWT). |
Change from Baseline at Week 96 in 6MWT |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
1. Change from Baseline in the Total Distance Walked During 6MWT at Week 144 (Week 48 of the Open-Label Extension Period)
2. Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96
3. Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96
4. Participants Ability to Rise Independently From the Floor, as indicated by a North Star Ambulatory Assessment (NSAA) Subscore
5. The Time to Loss of Ambulation (LOA)
6. Change From Baseline in the NSAA Total Score at Week 96 and Week 144
7. Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 96 and Week 144 |
1) Change from Baseline at week 144 ( week 48 of the open label extension period)
2) Change from Baseline at week 48 or 96
3) Change from Baseline at week 48 or 96
4) Week 96, Week 144
5) Baseline, Week 96, and Week 144
6) Change from Baseline at week 96 and 144
7) Change from Baseline at week 96 and 144
|
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Target Sample Size
|
Total Sample Size="222"
Sample Size from India="20"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
05/10/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
21/09/2016 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
None Yet |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible participants with out-of-frame deletion mutations amenable to exon 45 or 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 30 milligrams/kilograms (mg/kg) SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group) or placebo for up to 96 weeks (the placebo-controlled period of the trial). This will be followed by an open-label extension period in which all participants will receive open-label active treatment for 48 weeks (up to Week 144 of study). The study will enroll approximately 222 participants. Twice as many participants will be randomized to receive active treatment as will receive placebo (2:1 randomization).Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests, such as the 6-minute walk test (6MWT). All participants will undergo a muscle biopsy at baseline and a second muscle biopsy either at Week 48 or Week 96. Safety will be assessed through the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study. Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of both drugs.
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