A Phase 3, Randomised, Placebo-Controlled Trial of Arimoclomol in Amyotrophic Lateral Sclerosis
- Conditions
- motor neuron disease and Lou Ghering disease10029305
- Registration Number
- NL-OMON48938
- Lead Sponsor
- Orphazyme A/S
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 19
1. Capable of- and willing to- provide written informed consent and comply with
trial procedures.
2. Subject is male or female *18 years of age.
3. Subject meets revised El Escorial criteria for clinically possible,
clinically probable / clinically probable ALS laboratory-supported, clinically
definite ALS or clinically definite familial ALS laboratory-supported.
4. 18 months or less since first appearance of weakness (e.g. limb weakness,
dysarthria, dysphagia, shortness of breath).
5. ALSFRS-R *35 and erect (seated) SVC % predicted * 70% at Screening.
6. Able and willing to travel to the site, and in the investigator*s opinion is
likely to attend visits for at least 24 weeks.
7. All sexually active female subjects of child-bearing potential
(postmenarchal)* must agree not to intend to become pregnant and use a highly
effective method of contraception** during the trial through 1 month after the
last dose of trial medication. If the subject is a sexually active male with
female partners of child-bearing potential (postmenarchal) he must use a condom
with or without spermicide in addition to the birth control used by their
partners during the trial until 3 months after the last dose of trial
medication.
8. Stable dose of riluzole (50 mg twice daily) for a minimum of 14 days prior
to Day 1 (Baseline),or has not taken it for 14 days prior to Day 1.
1. Tracheostomy or use of non-invasive ventilation for more than 2 hours during
waking hours at the time of Screening and Baseline visits.
2. Pregnant or breast-feeding.
3. Current or anticipated use of diaphragmatic pacing during the trial.
4. Exposure to any investigational treatment within 4 weeks or <5 half-lives of
the Screening visit, whichever is longest and/or advanced therapy medicinal
product (ATMP), i.e. treatments based on genes, cells or tissues and/or
participated in any prior ALS clinical trial receiving active drug treatment
(with the exception described in exclusion criterion 5).
5. Treatment with edaravone within 4 weeks of the Baseline visit. However, up
to 18 subjects on stable (i.e. minimum 6 months*) treatment with edaravone and
who otherwise fulfil the eligibility criteria are planned for enrolment
(limited to countries where edaravone has a marketing authorisation for
treatment of ALS).
6. Any of the following medically significant conditions:
a) Neurological impairment/dysfunction or unstable psychiatric illness that in
the investigator*s opinion is likely to interfere with assessment of ALS
disease progression.
b) Clinically significant unstable medical condition other than ALS, which
would present a risk to a subject to participate in the trial
c) Presence of dementia that impairs the ability of the subject to provide
informed consent, according to the PI decision.
d) Known or suspected allergy or intolerance to the IMP (arimoclomol or
constituents);
e) Chronic infection particularly HIV or Hepatitis B or C.
f) Clinically significant renal or hepatic disease
g) Aspartate aminotransferase and/or alanine aminotransferase, and/or lactate
dehydrogenase *3 times the upper limit of normal [ULN], bilirubin*2 times the
ULN, or creatinine *1.5 times the ULN). Laboratory tests may be repeated once
at Screening. Reasons to repeat laboratory tests may include that the
medication causing laboratory abnormality was suspended, any other suspected
cause may no longer exist, or to rule out laboratory error.
h) Cancer that is currently under active treatment or is likely to require
treatment during the trial that may alter the subject*s function and thereby
interfere with assessment of ALS disease progression.
i) Any other condition that in the investigator*s opinion would present a risk
to a subject to participate in the trial, interfere with the assessment of
safety or has an increased risk of causing death during the trial.
* Non child-bearing potential is defined as post-menopausal (minimum of 12
months with no menses and follicle-stimulating hormone in the post-menopausal
range) or sterilisation (hysterectomy, oophorectomy, or bilateral tubal
ligation).** Highly effective methods of contraception include combined
(oestrogen and progestogen containing) hormonal contraception associated with
inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only
hormonal contraception associated with inhibition of ovulation (oral,
injectable, or implantable); intrauterine device; intrauterine
hormone-releasing system; bilateral tubal occlusion; and vasectomised
partner.According to the recommendations from the Clinical Trial Facilitation
Group (CTFG, 2014), sexual abstinence is considered a highly effective birth
control method only if
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint<br /><br>Combined assessment of function and survival (CAFS) over a treatment period of<br /><br>76 weeks (or end-of-trial)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints<br /><br>* Time to PAV/tracheostomy/death<br /><br>* Change from Baseline to Week 76 (or end-of-trial) in ALSFRS-R<br /><br>* Change from Baseline to Week 76 (or end-of-trial) in SVC </p><br>