Extension study of Arimoclomol in patients with amyotrophic lateral sclerosis.

• Register: EUCTR
• Last refreshed on: 11 May 2020
• Main ID: EUCTR2019-000374-39-GB
• Date of registration: 09/05/2019
• Prospective Registration: Yes
• Primary sponsor: Orphazyme A/S
• Public title: Extension study of Arimoclomol in patients with amyotrophic lateral sclerosis.
• Scientific title: Open-label, Non-randomised Extension Trial to Assess the Long-Term Safety and Efficacy of 1200 mg/day Arimoclomol 400 mg Three Times a Day (t.i.d.) in Subjects with Amyotrophic Lateral Sclerosis (ALS) who have Completed the ORARIALS-01 Trial
• Date of first enrolment: 15/07/2019
• Target sample size: 231
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000374-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• 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, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures.
2. Subject has completed the ORARIALS-01 trial (i.e., met one of the surrogate survival endpoints of tracheostomy or PAV or has completed the 76 weeks randomised treatment period).
3. Subject completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit. (whether at week 76 or prior).
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) yes
F.1.3.1 Number of subjects for this age range 71

Exclusion criteria:
1. Known or suspected allergy or intolerance to the IMP (arimoclomol or constituents).
2. Exposure to any other investigational treatment, advanced therapy medicinal product(ATMP) or use of any other prohibited concomitant medications.
3. Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication. Acceptable methods of birth control are:
a. Hormonal methods associated with inhibition of ovulation such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the subject’s usual menstrual cycle period) before IMP administration.
b. Total abstinence from sexual intercourse since the last menses before IMP administration. (The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence methods [calendar, symptothermal, post-ovulation methods] are not acceptable methods of contraception).
c. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS).
4. Any of the following medically significant conditions:
a. Clinically significant renal or hepatic disease OR clinical laboratory assessment (results = 3 times the upper limit of normal [ULN] for aspartate aminotransferase, and/or alanine aminotransferase, bilirubin = 2 times the ULN, or creatinine = 1.5 times the ULN).
b. Any new condition or worsening of existing condition which, in the opinion of the investigator would put the subject at undue risk.
5. Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP.


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

Health Condition(s) or Problem(s) studied

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

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

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-

Primary Outcome(s)

Secondary Objective: To evaluate the long-term efficacy of arimoclomol treatment of ALS.

Main Objective: To assess the long-term safety of arimoclomol treatment of ALS.

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

Primary end point(s): 1. Incidence and severity of TEAEs over a treatment period of 76 weeks
2. Mean and change from Baseline (of the present trial) to Week 76 (or end of trial) in clinical safety laboratory tests and vital signs
3. Incidence of potentially clinically significant abnormalities in clinical safety laboratory tests and vital signs over a treatment period of 76 weeks
4. C-SSRS over a treatment period of 76 weeks

Secondary Outcome(s)

Secondary end point(s): 1. Time to PAV/tracheostomy/death (for subjects entering this trial having completed 76 weeks of randomised treatment in ORARIALS-01)
2. Change in ALSFRS-R from Baseline (of the present trial) to the end of the trial
3. Change in SVC from Baseline (of the present trial) to the end of the trial (for subjects who did not meet the survival endpoint in the ORARIALS-01 trial)

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

Secondary ID(s)

ORARIALS-02

NCT03836716

Source(s) of Monetary Support

Orphazyme A/S

Ethics review

Status: Approved
Approval date: 15/07/2019
Contact: