This study has been transitioned to CTIS with ID 2023-507146-91-00 check the CTIS register for the current data. Primary Objective:• To evaluate the safety and tolerability of viltolarsen administered intravenously (IV) at weekly doses of 80 mg/kg…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints:
• Vital signs
• Physical examination
• Clinical laboratory tests: hematology and clinical chemistry, Urinalysis and
Urine cytology
• Antibodies to dystrophin and viltolarsen
• 12-lead electrocardiogram (ECG)
• Renal ultrasound
• Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Secondary outcome
Secondary Endpoints:
• Time to Stand Test (TTSTAND)
• Time to Run/Walk 10 Meters Test (TTRW)
• Six-minute Walk Test (6MWT)
• North Star Ambulatory Assessment (NSAA)
• Time to Climb 4 Stairs Test (TTCLIMB)
• Quantitative muscle strength measured by hand-held dynamometer (elbow
extension, elbow flexion, knee extension, and knee flexion on the dominant side
only)
Exploratory Endpoints:
• Pediatric Outcome Data Collection Instrument (PODCI)
• Personal Adjustment and Role Skills Scale, 3rd edition (PARS III)
Questionnaire
• Loss of ambulation
Background summary
DMD is a disorder of progressive weakness leading to severe disability and
ultimately death. Patients with DMD have mutations in dystrophin, a key muscle
protein. For making proteins our body uses a template (mRNA). DMD mutations
disrupt this template, leading to incorrect or no protein assembly with as
result a deficiency of the dystrophin protein. At present, glucocorticoid (GC)
medication is the only treatment that has been shown to slow the decline of
strength and function in DMD patients, however, this treatment can have
significant side effects. New therapies based on specific genetic makeups are
in development. Viltolarsen is designed to interact with the template used for
making the dystrophin protein and to correct for the errors introduced by these
mutations. The purpose of this study is to investigate how safe and effective
the new medicine viltolarsen is for the treatment of DMD.
Study objective
This study has been transitioned to CTIS with ID 2023-507146-91-00 check the CTIS register for the current data.
Primary Objective:
• To evaluate the safety and tolerability of viltolarsen administered
intravenously (IV) at weekly doses of 80 mg/kg in boys who have completed the
NS 065/NCNP 01-301 study.
Secondary Objective:
• To compare the efficacy of viltolarsen administered IV at weekly doses of 80
mg/kg in boys who have completed the NS 065/NCNP 01-301 study over a 96-week
treatment period versus natural history controls using strength and endurance
outcomes.
Exploratory Objectives:
• To evaluate health-related quality of life impact of viltolarsen treatment on
patient's DMD.
• To evaluate preservation of ambulation of patients with DMD.
Study design
This Phase 3 study is a multi-center, open-label extension study in ambulant
boys with DMD who have completed the 48 week treatment period of either
viltolarsen or placebo in Study NS 065/NCNP-01-301. Patients will receive
viltolarsen administered IV at weekly doses of 80 mg/kg. Study
NS-065/NCNP-01-302 will be comprised of a 96-week treatment period.
Intervention
Patients will receive IV infusions of viltolarsen injection administered once
weekly over a 96-week period. Patients will be dosed at 80 mg/kg/week.
Study burden and risks
Burden:
Participants have to visit the research center approximately 97 times, over a
period of 98 weeks. During each visit participants will receive the study drug
via infusion and additional medical test will be done. Some visits can take up
to 4 hours. (see section E4 and E6).
Risks and side effects related to the study drug and risks associated with
other study procedures.
The most common side effects of the study medicine (vitolarsen) are listed
below Diastolic blood pressure increased (5%), Changes in kidney function
(43%), Immune/allergic symptoms including rash and joint pain (7%), Impaired
ability of the heart to adequately pump blood through the body (7%), Infections
(48%). Cancer risk of Viltolarsen is unknown and is currently being
investigated in animal experiments. The potential risk in humans, however,
cannot be excluded at the present time. The study medicine may cause also side
effects that are unknown.
Risks of receiving an infusion: A rash or pain at the site of the infusion,
infection can also happen at the infusion site including redness, swelling, and
fever. Standard of care procedures for infusions will be followed to minimize
any risk of infusion specific related side effects.
Risks of port placement: The risks of the surgery to have the port placed
include bruising, scarring, prolonged bleeding from the operation site and
infection. Port placement will require anaesthesia. Additional risks of having
a port include clots forming in the port, failure of the port device so that it
needs to be removed or replaced, introduction of air between the lungs and the
chest wall such that the lungs collapse, and injury to a major blood vessel. As
with any surgery, there may be other unexpected risks or complications of this
surgery that are uncommon but serious, including death.
Risks of port use: The risks include infections, clots forming in the port or
in his vein (for example the vein that carries blood to his heart), a change in
position of the port so that it no longer works well or failure of the port
device so that it needs to be removed or replaced. Infection can become a
serious complication that in rare cases can lead to sepsis, shock, and/or
death. You and your child will be trained in the proper use and care of a port
to reduce these risks and to watch for any problems.
Risks of anaesthesia in DMD: As DMD affects the muscles, patients with DMD have
an increased risk of breathing distress from anaesthesia. General anaesthesia
may have increased risks including heart complications and death from general
anaesthesia. The study doctor will provide special instructions to the surgeon
performing the port placement, the selection of anaesthesia will be discussed
with you, and all steps to reduce risks will be taken.
Risks of blood sample collection: Risks associated with drawing blood from his
arm include momentary discomfort and/or bruising. Infection, excess bleeding,
and/or fainting are also possible, although unlikely. Rarely, a more serious
injury, such as bleeding under the skin (hematoma) may develop. To reduce
discomfort a local numbing cream may be applied. The side effects that may be
associated with the numbing cream include lack of sensation to the area where
the cream is applied
Renal Ultrasound Risks: There are no known risks. Discomfort is uncommon, but
your child will feel some pressure, and may need to drink extra fluids to have
a full bladder. Sometimes, an ultrasound may not be able to obtain the
pictures your study doctor needs, so other imaging tests may have to be
obtained.
Risk of electrocardiography: This test may cause irritation to the skin where
the electrodes are placed.
Risks of strength and function tests: It is possible that these tests could
make your child more tired than after a regular (non-research) doctor*s visit.
There is also a small risk of falling, shortness of breath, or muscle soreness.
East Ridgewood Avenue Suite 280S 140
Paramus, NJ 07652
US
East Ridgewood Avenue Suite 280S 140
Paramus, NJ 07652
US
Listed location countries
Age
Inclusion criteria
1. Patient has completed the NS-065/NCNP-01-301 study;
2. Patient*s parent(s) or legal guardian(s) has (have) provided written
informed consent and Health Insurance Portability and Accountability Act
authorization, where applicable, prior to any study-related procedures;
patients will be asked to give written or verbal assent according to local
requirements;
3. Patient and parent(s)/guardian(s) are willing and able to comply with
scheduled visits, investigational product (IP) administration plan, and study
procedures.
Exclusion criteria
1. Patient had an adverse event in Study NS 065/NCNP 01 301 that, in the
opinion of the investigator and/or the sponsor, precludes safe use of
viltolarsen for the patient in this study;
2. Patient had a treatment which was made for the purpose of dystrophin or
dystrophin-related protein induction after completion of Study
NS-065/NCNP-01-301.
3. Patient took any other investigational drug(s) during or after completion of
Study NS-065/NCNP-01-301.
4. Patient is judged by the investigator and/or the sponsor not to be
appropriate to participate in the extension study for any reason.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-507146-91-00 |
| EudraCT | EUCTR2021-000122-10-NL |
| ClinicalTrials.gov | NCT04060199 |
| CCMO | NL76990.000.21 |