The purpose of this study is to evaluate whether the new drug reldesemtiv is effective and safe in patients with ALS. The primary objective is to assess the effect of reldesemtiv versus placebo on functional outcomes in ALS.The secondary objectives…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study outcome is the change from baseline to Week 24 in ALSFRS-R
total score.
Secondary outcome
The secondary outcomes of study are:
• Combined assessment of change in ALSFRS-R total score, time to onset of
respiratory insufficiency, and survival time up to Week 24
• Change from baseline to Week 24 in the percent predicted FVC
• Change from baseline to Week 24 in the
ALSAQ-40 total score
• Change from baseline to Week 24 in handgrip strength (average of both hands).
Background summary
Reldesemtiv, a fast skeletal muscle troponin activator (FSTA), is being
investigated as a potential therapy to slow the decline of skeletal muscle
function in patients with ALS. This pivotal trial with reldesemtiv is being
conducted in ALS patients and is designed to assess the effect of reldesemtiv
on functional outcomes during treatment up to 48 weeks. The first trial with
reldesemtiv in ALS patients (FORTITUDE-ALS [CY 5022]) after 12 weeks of dosing,
showed that patients on all doses of reldesemtiv tended to decline less than
patients on placebo for slow vital capacity (SVC) and ALS Functional Rating
Scale-Revised (ALSFRS-R), with larger and clinically meaningful differences
emerging over time. The results support progression in a further clinical trial
with a longer dosing duration.
Study objective
The purpose of this study is to evaluate whether the new drug reldesemtiv is
effective and safe in patients with ALS.
The primary objective is to assess the effect of reldesemtiv versus placebo on
functional outcomes in ALS.
The secondary objectives are:
• To assess the effect of reldesemtiv versus placebo on combined functional and
survival outcomes in ALS
• To assess the effect of reldesemtiv versus placebo on ventilatory function
• To assess the effect of reldesemtiv versus placebo on quality of life
• To assess the effect of reldesemtiv versus placebo on handgrip strength.
Study design
This is a Phase 3, double-blind, randomized, placebo-controlled trial of
reldesemtiv in patients aged 18 to 80 with ALS.
The screening and qualification period for the trial will be no more than 14
days in duration. Approximately 555 eligible ALS patients will be randomized
(2:1) to receive the following dose of reldesemtiv or placebo (stratified by
riluzole use/non-use and edaravone use/non-use) for the first 24 weeks
(double-blind, placebo-controlled period):
• 300 mg reldesemtiv twice a day for a 600 mg total daily dose (TDD)
• Placebo twice daily
At the end of the 24-week double-blind, placebo-controlled period, patients
will transition to the active drug period, where all patients will receive the
following dose of reldesemtiv for the next 24 weeks:
• 300 mg reldesemtiv twice a day for a 600 mg TDD for patients who were not
down titrated during the 24 weeks of blinded dosing
• 150 mg reldesemtiv twice a day for a 300 mg TDD for patients who were down
titrated for any reason during the 24 weeks of blinded dosing
Intervention
• 300 mg reldesemtiv twice a day for a 600 mg total daily dose (TDD)
• Placebo twice daily
At the end of the 24-week double-blind, placebo-controlled period, patients
will transition to the active drug period, where all patients will receive the
following dose of reldesemtiv for the next 24 weeks:
• 300 mg reldesemtiv twice a day for a 600 mg TDD for patients who were not
down titrated during the 24 weeks of blinded dosing
• 150 mg reldesemtiv twice a day for a 300 mg TDD for patients who were down
titrated for any reason during the 24 weeks of blinded dosing
Study burden and risks
physical examination 2x
weight, BMI 8x
neurological examination 3x
ecg 5x
blood and urine sampling 17x
lung function tests16x
muscle strength tests 8x
questionnaires 15x
when participating in potential PK sub study: 7 additional blood samples
East Grand Avenue 280
South San Francisco CA 94080
US
East Grand Avenue 280
South San Francisco CA 94080
US
Listed location countries
Age
Inclusion criteria
Males or Females between the ages of 18 and 80 years of age, inclusive
• Diagnosis of familial or sporadic ALS (defined as meeting the
laboratory-supported probable, probable, or definite criteria for ALS according
to the World Federation of Neurology El Escorial criteria published in 2000
[Brooks 2000]). Patients who meet the possible criteria are eligible if they
have lower motor neuron findings; those who have purely upper motor neuron
findings are ineligible.
• First symptom of ALS <= 24 months prior to screening. The qualifying first
symptoms of ALS are limited to manifestations of weakness in extremity, bulbar,
or respiratory muscles. Cramps, fasciculations, or fatigue should not be taken
in isolation as a first symptom of ALS.
• ALSFRS-R total score <= 44 at screening. Patients with a total score of 45 or
higher may be rescreened 60±7 days following the original screening date and be
deemed eligible if their ALSFRS-R total score is <= 44 or if their score is 2 or
more points less than at initial screening.
Such patients must continue to meet all other inclusion/exclusion criteria at
the time of rescreening.
• Upright FVC >= 65.0% of predicted for age, height, sex and ethnicity at
screening according to
Global Lung Initiative equation
• Able to perform reproducible pulmonary function tests defined as being able
to perform FVC at screening with variability of the 2 highest raw values of
less than 10% with a maximum of 5 trials permitted. Screening FVC results must
be reviewed and approved by the central review process prior to randomization.
• Must be either on riluzole for >= 30 days prior to screening or have not taken
it for at least 30 days
prior to screening
• Must have completed at least 2 cycles of edaravone at the time of screening
or have not received it for at least 30 days prior to screening
• Able to swallow whole tablets at the time of screening
. Clinical laboratory findings within the normal range, or if outside the
normal range, not deemed clinically significant by the Investigator, except as
specifically indicated as laboratory exclusion
Exclusion criteria
• eGFRCr and eGFRCysC < 45.0 mL/min/1.73 m2 at screening
• Urine protein/creatinine ratio > 1 mg/mg (113 mg/mmol) at screening
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 3-times
the upper limit of normal (ULN)
• Total bilirubin (TBL), direct or indirect bilirubin above the ULN.
• Cognitive impairment, related to ALS or otherwise that impairs the patient*s
ability to understand and/or comply with study procedures and provide informed
consent
• Other medically significant neurological conditions that could interfere with
the assessment of ALS
symptoms, signs or progression.
• Presence at screening of any medically significant cardiac, pulmonary,
gastrointestinal, musculoskeletal, or psychiatric illness that might interfere
with the patient*s ability to comply with study procedures or that might
confound the interpretation of clinical safety or efficacy data
• Has a tracheostomy
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 | EUCTR2020-004040-29-NL |
| CCMO | NL77133.041.21 |