Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00706147
Recruitment Status : Completed
First Posted : June 27, 2008
Last Update Posted : January 11, 2019
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Michael Benatar, University of Miami

Tracking Information
First Submitted Date  ICMJE June 24, 2008
First Posted Date  ICMJE June 27, 2008
Last Update Posted Date January 11, 2019
Study Start Date  ICMJE January 2009
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2015)
Time to death, tracheostomy or permanent assisted ventilation will be the primary outcome measure. [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 26, 2008)
The primary objective of this study is to assess the safety and tolerability of arimoclomol, at a dosage of 100 mg three times per day, as compared with placebo over 6 months of treatment in 30 patients with SOD1 positive familial ALS. [ Time Frame: Seven months ]
Change History Complete list of historical versions of study NCT00706147 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2015)
  • Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of up to 12 months. [ Time Frame: 12 months ]
  • Disease progression as measured by the rate of decline of FEV6. [ Time Frame: 12 months ]
  • Safety and tolerability of arimoclomol will be evaluated by using vital signs and weight, clinical laboratory measures, physical examination, report of adverse events, and the proportion of subjects completing the study on assigned treatment. [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2008)
  • Demonstrate the feasibility of a new approach to the design of a clinical trial for a rare disease by having the coordinator travel to the patient's home to collect data, after the Baseline and Month-2 visits have been completed at the study site. [ Time Frame: Seven months ]
  • Formally evaluate the rate of disease progression in untreated participants using several standard outcome measures. [ Time Frame: Seven months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis
Official Title  ICMJE Phase II/III Randomized, Placebo-Controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis (ALS)
Brief Summary

The purpose of this study will be to demonstrate the safety, tolerability, and efficacy of arimoclomol in subjects with SOD1 positive familial Amyotrophic Lateral Sclerosis (ALS). This type of ALS is HEREDITARY (runs in families), and at least one other person in the family must have had ALS.

Study hypotheses: Arimoclomol, taken at a dose of 200 mg three times daily will improve survival as defined by time to death, tracheostomy or permanent assisted ventilation. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS.

Funding Source - FDA-OOPD

Detailed Description Using a seamless, adaptive, phase II/III design, the investigators will determine the safety and efficacy of arimoclomol in patients with SOD1 positive familial ALS. Both stage-1 and stage-2 are randomized, double-blind and placebo-controlled in a population of patients with rapidly progressive SOD1 positive familial ALS. Patients with ALS, a history of a relative affected with ALS (i.e. familial ALS) and the presence of a demonstrable mutation in the SOD1 gene that is known to be associated with rapidly progressive disease, will be eligible for inclusion in this study. Potentially eligible subjects will undergo screening via telephone and, if necessary, review of outside medical records. The intervention will continue for up to 12 months. In the event that a participant reaches a study endpoint (e.g. tracheostomy or permanently assisted ventilation) study drug will be terminated. Subjects who meet all eligibility criteria will travel a study site for final eligibility determination, baseline evaluation and will then be randomized 1:1 to receive either placebo or arimoclomol at a dose of 200 mg t.i.d. Participants will then be evaluated again in person at a study site at Month-2. Telephonic evaluations at Month-1, 3, 4, 5, 6, 8, and 10 will be performed in participants' homes. Safety and tolerability evaluations will be performed at each of these visits. Collection of blood samples for safety laboratory analyses and measurement of blood pressure, heart rate, respiratory rate, temperature and weight will be performed at Months-1, 3, 4, 5, 6, 8, and 10 in the participant's home by a representative of a medical monitoring company. A study coordinator may perform an in-person visit at Month-12, or this visit may occur telephonically. A final evaluation will be performed via telephone at Month-13 (30 days after the last dose of study medication).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Drug: Arimoclomol
    Drug: Arimoclomol capsules given three times per day
    Other Name: Arimoclomol (BRX-345)
  • Drug: Placebo
    Drug: Placebo capsules given three times per day
Study Arms  ICMJE
  • Placebo Comparator: 1
    Intervention: Drug: Placebo
  • Active Comparator: 2
    Intervention: Drug: Arimoclomol
Publications * Benatar M, Wuu J, Andersen PM, Atassi N, David W, Cudkowicz M, Schoenfeld D. Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS. Neurology. 2018 Feb 13;90(7):e565-e574. doi: 10.1212/WNL.0000000000004960. Epub 2018 Jan 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 10, 2017)
38
Original Estimated Enrollment  ICMJE
 (submitted: June 26, 2008)
30
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Type of ALS that is hereditary (runs in families) only.
  • El Escorial criteria for familial ALS and a family history of a pathogenic mutation in a gene known to be associated with ALS, such as the SOD1 gene.
  • Willingness to undergo genetic testing and to learn the results.
  • Demonstrable mutation in the SOD1 gene that is reported to be associated with a rapid rate of disease progression (i.e. A4V, A4T, C6F, C6G, V7E, L8Q, G10V, G41S, H43R, H48Q, D90V, G93A, D101H, D101Y, L106V, I112M, I112T, R115G, L126X, G127X, A145T, V148G, V148I) or possibly associated with rapidly progressive disease (E21G, G37R, L38V, D76Y, L84F, L84V, N86S, D90A het, G93R, I104F, I113T, L144F, L144S).
  • Age 18 years or older; male or female.
  • Capable of providing informed consent and complying with trial procedures.
  • Diagnosis within less than 9 months of the anticipated date of the baseline visit AND study participants' subjective evaluation that they expect their physical condition to permit travel to the study site for both the baseline and 2-month study visits.
  • Women must not be able to become pregnant (e.g. post menopausal for at least one year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Adequate contraception includes: oral contraception, implanted contraception, intrauterine device in place for at least 3 months, or barrier method in conjunction with spermicide.
  • Women of childbearing potential must have a negative pregnancy test at screening visit and be non-lactating.
  • Willing to remain on a stable dose of Riluzole or to remain off Riluzole for the duration of the trial.
  • Identifiable local medical doctor to assist with urgent care of any medical complications that may arise.
  • Absence of any of the exclusion criteria.

Exclusion Criteria:

  • History of known sensitivity or intolerability to Arimoclomol or to any other related compound.
  • Exposure to any investigational drug within 30 days of the screening visit.
  • Presence of any of the following clinical conditions:

    • Substance abuse within the past year.
    • Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease.
    • AIDS or AIDS-related complex.
    • Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression within 90 days of the screening visit.
    • Positive pregnancy test at screening visit.
  • Screening laboratory values:

    • Creatinine greater than 1.5.
    • Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST). greater than 3.0 times the upper limit of normal.
    • Total bilirubin greater than 2.0 times the upper limit of normal.
    • White blood cell (WBC) count less than 3,500/mm3.
    • Platelet concentration less than 100,000/ul.
    • Hematocrit level less than 33 for female or less than 35 for male.
  • Female patients who are breast-feeding.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00706147
Other Study ID Numbers  ICMJE 20100758
3517 ( Other Grant/Funding Number: OOPD )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Michael Benatar, University of Miami
Study Sponsor  ICMJE University of Miami
Collaborators  ICMJE Massachusetts General Hospital
Investigators  ICMJE
Principal Investigator: Michael Benatar, MBChB, DPhil University of Miami
Principal Investigator: Merit Cudkowicz, MD, MSc Massachusetts General Hospital
PRS Account University of Miami
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP