This study has been transitioned to CTIS with ID 2024-514082-19-00 check the CTIS register for the current data. The aim of this phase 2 study is to investigate the safety and efficacy of dazucorilant in the target ALS patient population.
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint
• Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised
(ALSFRS-R) total
score.
Primary Safety Endpoint
• Incidence of AEs, SAEs, treatment-related AEs, AEs by severity, and deaths
due to AEs.
Secondary outcome
• Change from Baseline to Week 24 in muscle strength (assessed using hand-held
dynamometer).
• Change from Baseline to Week 24 in:
* Percent Slow Vital Capacity
* EQ-5D-5L.
• Time to death.
• Time to respiratory support >22 hours per day for 7 days.
• Time to death or time to respiratory support >22 hours per day for 7 days.
• Combined Assessment of Function and Survival (CAFS).
• Plasma samples for pharmacokinetic (PK) analysis will be obtained in a
dedicated PK substudy in a subset (~20%) of patients at the Week 3 visit. The
dazucorilant AUC and Cmax will be reported.
Background summary
Amyotrophic lateral sclerosis (ALS) is a rare and fatal condition with
insufficient treatment options. It is characterized by progressive degeneration
of motor neurons in both the brain and spinal cord and leads to progressive
muscle weakness, relentless disability and, generally, death within 3-5 years
of the onset of symptoms. There are limited pharmacological options in ALS and
they are mainly aimed at symptomatic treatment. The only existing authorized
drug for the treatment of ALS in the European Union is Riluzole.
Dazucorilant has been selected for development based on promising results in
mouse models of ALS. Efficacy has been demonstrated in the Wobbler mouse, a
widely recognized model of ALS. Administration of dazucorilant for 21 days
improved many aspects of the disease in these mice, including reducing forelimb
atrophy, overcoming impaired performance in the rotarod test, and inhibiting
neurodegeneration and inflammation.
In the phase 1 studies with dazucorilant, no significant safety risks were
found and the most common side effects of dazucorilant were gastrointestinal
complaints, headache and back pain.
Study objective
This study has been transitioned to CTIS with ID 2024-514082-19-00 check the CTIS register for the current data.
The aim of this phase 2 study is to investigate the safety and efficacy of
dazucorilant in the target ALS patient population.
Study design
This is a multicenter, parallel-arm, placebo-controlled randomized,
double-blind study. Adults meeting all inclusion and exclusion criteria will be
randomized to one of three treatment arms in a 1:1:1 ratio. In the 24-week
double-blind treatment period, patients will be randomized to receive 150 mg of
CORT113176, 300 mg of CORT113176, or a corresponding placebo once daily for 24
weeks. Randomization will be stratified by prior use of ALS drugs riluzole
and/or edaravone (yes/no) and region of disease onset (bulbar/other). Study
visits will be once every three weeks. Visits in weeks 9, 15 and 21 during the
treatment period are remote and by telephone.
Patients who participated in the double-blind treatment period (i.e., completed
all visits) are eligible to participate in a 132-week open-label extension
(OLE) study. Participation in the OLE study is voluntary and a new informed
consent form must be signed. Patients that have chosen to participate in the
OLE must be enrolled within 28 days of the week 24 visit of the double-blind
period. Clinic visits will be at baseline and in OLE-week 4, 12, 20, 24, 36,
52, 84, 100 and 116. Phone visits will take place in weeks 8, 16 and 20. A
follow-up telephone visit will take place after 4 weeks at the end of the
OLE-treatment (OLE-week 136) to collect safety information.
Patients who complete the double-blind treatment period and who choose not to
participate in the OLE study enter the follow-up period of 132 weeks. Patients
are contacted by telephone 4, 12, 24, 48, 74, 96, 120 and 132 weeks
post-treatment to collect safety information and long-term follow-up
information.
If a patient participate to the randomised, double-blind study and the OLE
part, the maximal study duration for a patient would be 168 weeks.
Intervention
Patients are randomized in a 1:1:1 ratio to receive CORT113176 150 mg,
CORT113176 300 mg, or placebo once daily. All patients, regardless of the arm
to which they were randomized, will take one dose (corresponding to 4
capsules/dose) per day. Study drug is administered orally once daily with food
and 240 ml of water, at approximately the same time each day.
Study burden and risks
The study medication may have side effects. It cannot be excluded that side
effects will be serious, long lasting or permanent. All options will be used to
minimize any discomfort. These side effects were found in previous studies with
dazucorilant:
• abdominal pain (in about three in ten volunteers)
• abdominal discomfort (in about four in ten volunteers)
• back pain (in about two in ten volunteers)
• constipation (in about one in ten volunteers)
• diarrhea (in about one in ten volunteers)
• indigestion, or digestive complaints (in about one in ten volunteers)
• headache (in about seven in ten volunteers)
• decrease in platelet count in less than one in ten volunteers) during the
treatment period.
The study medication may also have side effects that we don't know yet.
Other disadvantages are possible negative consequences as a result of the
measurements during the study. In addition, the participant is asked to invest
time in the study, visit the hospital for study visits and undergo research
procedures.
Participating in this study may have medical benefits, but it is not certain.
By participating, the participant can help physicians better understand the
safety of the study drug and how well it works for the treatment of ALS. This
may be valuable in the future for new patients with ALS.
Commonwealth Drive 149
Menlo Park, California 94025
US
Commonwealth Drive 149
Menlo Park, California 94025
US
Listed location countries
Age
Inclusion criteria
1. Male and female patients >=18 years of age with ALS as defined by Gold Coast
Criteria.
2. Patients with sporadic or familial ALS with a risk of ALS progression
characterized by an ENCALS risk profile score >=-6 and <= -3.
3.Regulatory-authority-approved therapies for the treatment of ALS are
permitted. If taking riluzole and/or edaravone, and/or sodium phenylbutryte
and taurursodial, must have been on a stable dose of riluzole for >=30 days
and/or edaravone for >=60 days and/or sodium phenylbutyrate and taurursodial
maintenance dosage >=30 days prior to Screening.
4. Medically able to undergo the study procedures and to adhere to the visit
schedule at the time of study entry, as determined by the Investigator.
5. Able to understand the purpose and risks of the study; willing and able to
adhere to scheduled visits, treatment plans, laboratory tests, and other study
evaluations and procedures.
6. Provide written informed consent for participation in the study.
7. Male patients and female patients of childbearing potential must agree to
use a protocol-specified method of contraception from screening and during the
study until 28 days after last dose of study drug.
Exclusion criteria
1. History of a clinically significant non-ALS neurologic disorder, including,
but not limited to, muscular dystrophy, spinal stenosis, peripheral neuropathy,
inherited neuropathies, Alzheimer*s disease, cervical spondylosis, Parkinson*s
disease, Lewy body dementia, vascular dementia, Huntington*s disease, epilepsy,
stroke, multiple sclerosis, multifocal motor neuropathy, diabetic neuropathy,
brain tumor, or brain infection/abscess. 2. Inability to swallow capsules. 3.
Blood platelet count <150,000/mm3. 4. Renal impairment indicated by eGFR <=30
mL/min/1.73m2. 5. Human immunodeficiency virus (HIV) or current chronic/active
infection with hepatitis C virus or hepatitis B virus including patients with
chronic or active hepatitis B as diagnosed by serologic tests. 6. Women who are
pregnant, planning to become pregnant, or are breastfeeding. Women of
childbearing potential who are unwilling or unable to use highly effective
method of contraception from screening through the duration of treatment and up
to 28 days after last dose of study drug. 7. Known liver impairment (Child-Pugh
Class A, B, or C). 8. History of Class III/IV heart failure (per New York Heart
Association). 9. At the time of Screening, any use of non-invasive ventilation
(NIV), e.g., continuous positive airway pressure [CPAP], noninvasive bi-level
positive airway pressure [NPPV] or noninvasive volume ventilation [NVV] for any
portion of the day, or mechanical ventilation via tracheostomy, or on any form
of oxygen supplementation. 10. Any form of cancer within the 5 years before
first dose in this study (with the exception of basal cell and/or squamous cell
cancer of the skin that has been treated completely and is without evidence of
local recurrence or metastasis). 11. History of any other clinically
significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory,
gastrointestinal (GI), bleeding, autoimmune, neurological, psychiatric
disorder, or unstable medical condition (other than ALS), as judged by the
Investigator. 12. History and/or symptoms of adrenal insufficiency. 13.
Abnormal liver function defined as aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) >3 × upper limit of normal (ULN). 14. QTcF interval
based on the mean of 2 ECGs of >450 ms, for men and >470 ms for women. 15.
History of additional risk factors for torsades de pointes (e.g., heart
failure, hypokalemia, family history of long-QT syndrome). 16. Positive
nasopharyngeal PCR test for SARS-CoV-2 on Day -1 or within 8 weeks prior to
Screening. 17. Ongoing use of any strong CYP3A4 inhibitor/inducer or any
medication with a narrow therapeutic index that is predominantly metabolized by
CYP2C8. 18. Taking, or have taken, any strong CYP3A inducer within 30 days (or
5 half-lives if longer) before Screening, or any strong CYP3A inhibitor within
14 days before Screening. 19. Current or anticipated need, in the opinion of
the Investigator, of a diaphragm pacing system (DPS) during the study period.
20. Received any live or attenuated vaccine within 30 days, before the first
dose of study drug. Exceptions may apply on a case-by-case basis, if considered
not to interfere with the objectives of the study, as agreed by the PI and the
Corcept Medical Monitor. 21. Currently using glucocorticoids or have a history
of regular systemic glucocorticoid use at any dose within the last 12 months or
3 months for inhaled products before first dose of study drug. (Patients who
have stopped glucocorticoid use should have an alternative option if their
condition deteriorates during the study.) 22. Participation in a clinical trial
for ALS involving small molecules within 30 days of the Screening, or treatment
with another investigational drug (including through compassionate use
programs), biological agent, or device within 30 days or 5 half-lives of study
agent, whichever is longer. No prior treatment with small interfering RNA, stem
cell therapy, or gene therapy is allowed at any time in the patient*s history.
23. Unstable or poorly controlled comorbid disease process of any organ system
currently requiring active treatment or likely to require treatment adjustment
during the study. 24. Previous exposure or treatment with glucocorticoid
receptor modulators or antagonists. 25. History of hypersensitivity or severe
reaction to the study drug*s excipients. 26. In the Investigator*s opinion,
should not participate in the study or may not be capable of providing informed
consent or following the study schedule. This includes, but is not limited to,
presence of unstable psychiatric disease, cognitive impairment, dementia, or
substance abuse within 2 years prior to Screening. 27. Is a family member of
one of the Sponsor*s employees, the Investigator, or the site staff working
directly on the study.
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 | CTIS2024-514082-19-00 |
| EudraCT | EUCTR2021-005611-31-NL |
| CCMO | NL80995.041.22 |