A study to compare the use of Arimoclomol with placebo in patients with Amyotrophic Lateral Sclerosis

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2018-000137-13-NL
• Date of registration: 18/09/2018
• Prospective Registration: Yes
• Primary sponsor: Orphazyme A/S
• Public title: A study to compare the use of Arimoclomol with placebo in patients with Amyotrophic Lateral Sclerosis
• Scientific title: A Phase 3, Randomised, Placebo-Controlled Trial of Arimoclomol in Amyotrophic Lateral Sclerosis
• Date of first enrolment: 21/11/2018
• Target sample size: 231
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000137-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Senior Clinical Project Manager
• Affiliation: Orphazyme A/S

• Name: Senior Clinical Project Manager
• Affiliation: Orphazyme A/S

Key inclusion & exclusion criteria

Inclusion criteria:
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 ALS, or 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 71

Exclusion criteria:
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. EExposure to any investigational treatment within 4 weeks or <5
halflives 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 it is defined as refraining from heterosexual intercourse during the trial until 1 week after the last dose of trial medication (for female subjects of child

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis
MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Arimoclomol
Product Code: BRX-345
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ARIMOCLOMOL
CAS Number: 368860-21-3
Current Sponsor code: BRX-345
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To determine the efficacy of chronic treatment with arimoclomol 1200 mg/day (400 mg TID) compared to placebo over 76 weeks in subjects with ALS as assessed with Combined Assessment of Function and Survival (CAFS)

Primary end point(s): Combined assessment of function and survival (CAFS) over a treatment period of 76 weeks (or end-of-trial)

Secondary Objective: To evaluate the impact of arimoclomol 1200 mg/day (400 mg TID) compared to placebo on:
• Time to permanent assisted ventilation (PAV)/tracheostomy free survival
• Disease progression as measured by change from Baseline of the ALSFRS-R
• Progression of respiratory dysfunction as measured by change from Baseline of the slow vital capacity (SVC)

Timepoint(s) of evaluation of this end point: 76 weeks (or end-of-trial)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 76 weeks (or end-of-trial)

Secondary end point(s): • Time to PAV/tracheostomy/death
• Change from Baseline to Week 76 (or end-of-trial) in ALSFRS-R
• Change from Baseline to Week 76 (or end-of-trial) in SVC

Secondary ID(s)

2018-000137-13-FR

ORARIALS-01

NCT03491462

Source(s) of Monetary Support

Orphazyme A/S

Ethics review

Status: Approved
Approval date: 21/11/2018
Contact: