Primary:• To compare the efficacy of viltolarsen administered intravenously (IV) at weekly doses of 80 mg/kg over a 48-week treatment period vs. placebo controls in ambulant boys ages 4 to
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• TTSTAND at 48 weeks of treatment
Secondary outcome
Hierarchical analysis at 48 weeks treatment of the following strength and
endurance measures:
• TTRW
• 6MWT
• NSAA
• TTCLIMB
• Quantitative muscle strength measured by hand-held dynamometer (elbow
extension, elbow flexion, knee extension and knee flexion on the dominant side
only)
• Vital signs (blood pressure, heart rate, respiratory rate, and body
temperature [modality for determining temperature should be consistent for each
participant at all assessment time points throughout the study])
• Physical examination
• Clinical laboratory tests:
• Hematology and clinical chemistry
• Urinalysis
• Urine cytology
• Exogenous tracer glomerular filtration rate (GFR)
• Antibodies to dystrophin and viltolarsen
• 12-lead electrocardiogram (ECG)
• Clinical signs and symptoms (AEs and SAEs)
• Grading of clinical and clinical laboratory AEs will be according to the
Common Terminology Criteria for Adverse Events (CTCAE), v.4.03
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. Doctors cannot prescribe
viltolarsen yet (outside a study). The efficacy of viltolarsen will be compared
to the efficacy of a placebo. A placebo is a medicine without any active
ingredient. It is a *fake* medicine.
Study objective
Primary:
• To compare the efficacy of viltolarsen administered intravenously (IV) at
weekly doses of 80 mg/kg over a 48-week treatment period vs. placebo controls
in ambulant boys ages 4 to <8 years with DMD using the Time to Stand Test
(TTSTAND) as a measure of strength and function.
Secondary:
• To compare the efficacy of viltolarsen administered IV at weekly doses of 80
mg/kg in ambulant boys ages 4 to <8 years with DMD over a 48-week treatment
period vs. placebo controls using hierarchical strength and endurance outcomes
• To evaluate the safety and tolerability of viltolarsen administered IV at
weekly doses of 80 mg/kg in ambulant boys ages 4 to <8 years with DMD
Exploratory:
• To evaluate health-related quality of life impact of viltolarsen treatment on
participant*s DMD.
Study design
This Phase 3 study is a randomized, double-blind, placebo-controlled,
multi-center study in ambulant boys ages 4 to <8 years with DMD receiving 80
mg/kg viltolarsen administered IV weekly over a 48-week treatment period.
Participants are randomly assigned to either 80 mg/kg/week viltolarsen or
placebo in a 1:1 ratio.
Group 1:
• 37 participants
• Viltolarsen 80mg/kg/week
Group 2:
• 37 participants
• Placebo
Intervention
Intravenous administration of the study drug.
Study burden and risks
Burden: 50 visits to the clinic, 1 phone call, renal ultrasounds, performing
function and strength tests, collecting blood and urine samples and completing
2 questionnaires, undergoing ECGs and GFR assessment with an exogenous tracer
Risks: 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.
The procedures and tests performed in this study have several risks which are
listed below:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Risk of electrocardiography: This test may cause irritation to the skin
where the electrodes are placed.
8. Risk of Exogenous tracer GFR test: For this test it might be necessary
to inject a very small amount of radioactive tracer (depending of the procedure
at your child*s hospital) in order to measure your child*s GFR. The very small
risk from this is outweighed by the information that will be gained by the
measurement. It is very unlikely that your child will feel any side-effects
after the test, but if you think he has please let your child*s doctor know.
9. 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. Participant*s parent(s) or legal guardian(s) has (have) provided written
informed consent and Health Insurance Portability and Accountability Act
(HIPAA) authorization, where applicable, prior to any study-related procedures;
participants will be asked to give written or verbal assent according to local
requirements
2. Participant has a confirmed diagnosis of DMD defined as:
a. Participant is male with clinical signs compatible with DMD; and
b. Participant has a confirmed DMD mutation(s) in the dystrophin gene that is
amenable to skipping of exon 53 to restore the dystrophin mRNA reading frame
including determination of unambiguously defined exon boundaries (using
techniques such as Multiplex Ligation-dependent Probe Amplification [MLPA],
comparative genomic hybridization [CGH] array or other techniques with similar
capability)
3. Participant is >= 4 years and <8 years of age at time of first infusion in
the study
4. Participant is able to walk independently without assistive devices
5. Participant is able to complete the TTSTAND without assistance in <10
seconds, as assessed at the Screening Visit and the Pre-infusion Visit (Note:
The TTSTAND performed independently from the NSAA should be used to determine
eligibility)
6. Participant and parent(s)/guardian(s) are willing and able to comply with
scheduled visits, study drug administration plan, and study procedures
7. Participant must be on a stable dose of glucocorticoid (GC) for at least 3
months prior to first dose of study drug and is expected to remain on the
stable dose of GC treatment for the duration of the study
Exclusion criteria
1. Participant has current or history of chronic systemic fungal or viral
infections
2. Participant has had an acute illness within 4 weeks prior to the first dose
of study drug based on the Principal Investigator*s judgment/discretion
3. Participant has evidence of symptomatic cardiomyopathy (Note: Asymptomatic
cardiac abnormality on investigation would not be exclusionary)
4. Participant has an allergy or hypersensitivity to the study drug or to any
of its constituents
5. Participant has severe behavioral or cognitive problems that preclude
participation in the study, in the opinion of the investigator
6. Participant has a previous or ongoing medical condition, medical history,
physical findings or laboratory abnormalities that could affect participant
safety, make it unlikely that treatment and follow-up will be correctly
completed or impair the assessment of study results, in the opinion of the
investigator
7. Participant has had surgery within the 3 months prior to the first
anticipated administration of study drug or surgery is planned for anytime
during the duration of the study
8. Participant has positive test results for hepatitis B antigen, hepatitis C
antibody or human immunodeficiency virus (HIV) antibody at screening. (Note: A
positive hepatitis C antibody result is acceptable if accompanied by a negative
hepatitis C RNA test and normal bilirubin and gamma glutamyl transferase
results.)
9. Participant is currently taking any other investigational drug or has taken
any other investigational drug within 3 months prior to the first dose of study
drug or within 5 times the half-life of a medication, whichever is longer
10. Participant was previously enrolled in an interventional study of
viltolarsen
11. Participant is currently taking any other exon skipping agent or has taken
any other exon skipping agent within 3 months prior to the first dose of study
drug
12. Participant has taken any gene therapy
13. Participant is currently taking idebenone, anabolic steroids (e.g.,
oxandrolone), or products containing resveratrol or adenosine triphosphate, or
has taken such within 3 months prior to first dose of study drug. Coenzyme Q10
or creatine are permitted only if the participant is receiving a stable dose
for at least 3 months prior to the first dose of study drug and for the
duration of the study
14. Note: There is no exclusion criterion #14. This criterion was removed from
the protocol with Amendment 4 (version 3.0, dated 08 January 2021); however,
the numbering was maintained to avoid documentation errors;
15. Participant has hydronephrosis, hydroureter, renal or urinary tract
calculi, or ureteral stenosis by medical history or renal ultrasound.
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 |
|---|---|
| EudraCT | EUCTR2019-002076-13-NL |
| CCMO | NL70538.000.19 |