Clinical Trial Results:
A Phase 2 Open-label Study to Assess the Safety, Tolerability, and Efficacy of Viltolarsen in Ambulant and Non-Ambulant Boys with Duchenne Muscular Dystrophy (DMD) Compared to Natural History Controls
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Summary
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EudraCT number |
2020-003653-30 |
Trial protocol |
IT ES |
Global end of trial date |
13 Jul 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Mar 2024
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First version publication date |
06 Mar 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NS-065/NCNP-01-211
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04956289 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
US IND: 127474 | ||
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Sponsors
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Sponsor organisation name |
NS Pharma, Inc.
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Sponsor organisation address |
140 East Ridgewood Ave, Suite 280S Paramus, NJ , NJ, United States, NJ 07652
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Public contact |
Clinical Trial Management, Medpace, 001 51357999111270, regsubmissions@medpace.com
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Scientific contact |
Clinical Trial Management, Medpace, 001 51357999111270, regsubmissions@medpace.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-002853-PIP01-20 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Dec 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Jul 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jul 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety and tolerability of viltolarsen administered intravenously (IV) at weekly doses of 80 mg/kg in ambulant and non ambulant boys >= 8 years of age with DMD
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Protection of trial subjects |
All considerations regarding the protection of human subjects were carried out in accordance with the protocol, GCP, ICH Guidelines, the ethical principles that have their origin in the Declaration of Helsinki, and all applicable regulatory requirements. The investigator (according to applicable regulatory requirements) or a person designated by the investigator and under the investigator’s responsibility fully informed patients of all pertinent aspects of the clinical trial.
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Background therapy |
Not applicable. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
05 Apr 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Italy: 3
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Country: Number of subjects enrolled |
China: 4
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Country: Number of subjects enrolled |
Russian Federation: 5
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Country: Number of subjects enrolled |
Türkiye: 5
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Country: Number of subjects enrolled |
United States: 2
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Worldwide total number of subjects |
20
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EEA total number of subjects |
4
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
13
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Adolescents (12-17 years) |
4
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Adults (18-64 years) |
3
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Twenty-one (21) patients were screened. Five patients were screen failed (4 patients due to reasons related to COVID-19 and 1 patient due to failure to satisfy exclusion criterion 1) and were rescreened and dosed. One patient was screen failure due to failure to satisfy exclusion criterion 5 and was not dosed. Twenty (20) patients were dosed. | ||||||
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Pre-assignment
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Screening details |
Ambulant and non-ambulant boys ≥8 years of age with a confirmed diagnosis of Duchenne Muscular Dystrophy (DMD), who had a Brooke scale rating of 3 or better OR an upright Forced Vital Capacity (FVC) 30% or greater at Screening, on a stable dose of glucocorticoid (GC) or were not treated with GC for at least 3 months prior to the first dose. | ||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not applicable.
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Arms
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Arm title
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Viltolarsen 80 mg/kg | ||||||
Arm description |
Patients received IV infusions of viltolarsen injection administered once weekly over a 48-week period. Patients were dosed at 80 mg/kg/week. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Viltolarsen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Viltolarsen injection 250 mg aqueous infusion was supplied as a 5 mL glass vial containing 50 mg/mL of drug substance solution in saline.
Patients received IV infusions of viltolarsen injection administered once weekly over a 48-week period. Patients were dosed at 80 mg/kg/week.
Viltolarsen is a novel antisense oligonucleotide for the treatment of DMD. Viltolarsen is designed to interact with the dystrophin gene ribonucleic acid (RNA) and alter the exon/intron splicing patterns. The mechanism of action for viltolarsen is to bind to a specific sequence in or near exon 53 of the dystrophin pre-RNA transcript and block the exon/intron splicing of exon 53, leading to mature mRNA transcripts that lack exon 53. The loss of exon 53 restores the mRNA reading frame, thus converting a DMD (out-of-frame) deletion mutation to a Becker-like (in frame) deletion mutation.
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Baseline characteristics reporting groups
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Reporting group title |
Viltolarsen 80 mg/kg
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Reporting group description |
Patients received IV infusions of viltolarsen injection administered once weekly over a 48-week period. Patients were dosed at 80 mg/kg/week. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Safety Population consisted of all patients who received at least 1 dose of IP (Investigational Product). This was the primary analysis population for the evaluation of safety. It includes all patients treated with viltolarsen both ambulant (10) and non-ambulant (10).
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End points reporting groups
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Reporting group title |
Viltolarsen 80 mg/kg
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Reporting group description |
Patients received IV infusions of viltolarsen injection administered once weekly over a 48-week period. Patients were dosed at 80 mg/kg/week. | ||
Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The Safety Population consisted of all patients who received at least 1 dose of IP (Investigational Product). This was the primary analysis population for the evaluation of safety. It includes all patients treated with viltolarsen both ambulant (10) and non-ambulant (10).
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End point title |
Treatment Related Adverse Events [1] | ||||||
End point description |
Number of participants with treatment related Adverse Events as assessed by CTCAE v4.03.
19 (95.0%) patients experienced a total of 66 TEAEs.
The maximum severity of TEAEs was mild for 7 (35.0%) patients and moderate in 12 (60.0%) patients. No patients experienced a severe TEAE.
2 (10.0%) patients experienced a TEAE which led to interruption in dosing. Most (17 [85.0%]) patients experienced TEAEs that were considered recovered or resolved. Two (10.0%) patients experienced TEAEs that were considered not recovered or resolved.
4 (20.0%) patients experienced a total of 4 IP-related TEAEs.
The maximum severity of IP related TEAEs was mild for 3 (15.0%) patients and moderate in 1 (5.0%) patient. No patients experienced a severe IP-related TEAE.
One (5.0%) patient experienced an IP-related TEAE that resulted in interruption in dosing. All IP related TEAEs were considered recovered or resolved.
Five (25.0%) patients experienced a total of 6 AESIs (Adverse event of special interest).
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End point type |
Primary
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End point timeframe |
Baseline to up to 48 weeks of treatment.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was performed for this endpoint. The information has been introduced in the section "Adverse Events". |
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
TEAEs were defined as any adverse events (AEs) that started on or after first dose of IP through 30 days after completion of study participation.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Safety Population
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Reporting group description |
The Safety Population consisted of all patients who received at least 1 dose of IP. This was the primary analysis population for the evaluation of safety. It includes all patients treated with viltolarsen both ambulant (10) and non-ambulant (10). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Mar 2022 |
The original Protocol (Version 1.0) was dated 21 January 2021. There was 1 global Amendment and 2 China-specific Amendments to the original Protocol. There were 4 Administrative Letters.
This amendment was developed to specify the minimum number of ambulant patients to be enrolled in the study (a minimum of 8); to clarify a location of blood sampling during the investigational product infusion and post-infusion; to specify the blood draw volumes; to clarify time points when viltorasen levels in plasma will be assessed; and to add necessary clarifications to the home infusion option. In addition, the details of the Performance of Upper Limb 2.0 assessment were added, as was clarification of referencing the United States package insert for the purpose of expedited reporting to the United States Food and Drug Administration and the United States sites. The general considerations of planned statistical methods were updated. A section describing disclosure of data was added to the protocol appendices. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
