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

Sponsor:	University of Miami
Collaborators:	ALS Association FDA Office of Orphan Products Development Massachusetts General Hospital
Information provided by (Responsible Party):	Michael Benatar, University of Miami
ClinicalTrials.gov Identifier:	NCT00706147

Purpose

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 reduce by at least 30% the rate of progression of disease. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS.

Condition	Intervention	Phase
Amyotrophic Lateral Sclerosis 1 Acquired Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis	Drug: Arimoclomol	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Phase II/III Randomized, Placebo-Controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:

Genetics Home Reference related topics: amyotrophic lateral sclerosis Help Me Understand Genetics

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

Drug Information available for: Arimoclomol

U.S. FDA Resources

Further study details as provided by University of Miami:

Primary Outcome Measures:

Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of 12 months will be the primary outcome measure. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease progression as measured by the rate of decline of FEV6 and MUNE. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Time to death, tracheostomy or permanent assisted ventilation will be the secondary endpoint. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	January 2009
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: 1	Drug: Arimoclomol Drug: Placebo capsules given three times per day Drug: Arimoclomol capsules given three times per day Other Name: Arimoclomol (BRX-345)
Active Comparator: 2	Drug: Arimoclomol Drug: Placebo capsules given three times per day Drug: Arimoclomol capsules given three times per day Other Name: Arimoclomol (BRX-345)

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. 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. Subsequent telephonic evaluations at Month-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, -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).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.
Not taking riluzole, or on a stable dose for at least thirty days prior to the baseline visit.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706147

Contacts

Contact: Margaret Walker, PhD	305-951-9326	mwalker@med.miami.edu
Contact: Michael Benatar, MBChB, DPhil	305-243-6480	mbenatar@med.miami.edu

Locations

United States, California
University of California, Irvine	Recruiting
Orange, California, United States, 92868
Contact: Tahseen Mozaffar, MD 714-456-2332 mozaffar@uci.edu
Contact: Veronica Martin, BA 714-469-8422 vero@uci.edu
Principal Investigator: Tahseen Mozaffar, MD
United States, Florida
University of Miami Miller School of Medicine	Recruiting
Miami, Florida, United States, 33136
Contact: Margaret Walker, PhD 305-951-9326 mwalker@med.miami.edu
Contact: Michael Benatar 305-243-6480 mbenatar@med.miami.edu
Principal Investigator: Michael Benatar, MBChB, DPhil
United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Nazem Atassi, MD, MSc 617-643-0842 natassi@partners.org
Contact: Robert J. Lawson 617-726-0563 rjlawson@partners.org
Principal Investigator: Nazem Atassi, MD

Sponsors and Collaborators

University of Miami

ALS Association

FDA Office of Orphan Products Development

Massachusetts General Hospital

Investigators

Principal Investigator:	Michael Benatar, MBChB, DPhil	University of Miami
Principal Investigator:	Merit Cudkowicz, MD, MSc	Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Michael Benatar, Associate Professor, Department of Neurology, University of Miami
ClinicalTrials.gov Identifier:	NCT00706147 History of Changes
Other Study ID Numbers:	Arimoclomol in SOD1 fALS
Study First Received:	June 24, 2008
Last Updated:	December 7, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami:

Hereditary ALS
Hereditary neurological disease
Lou Gehrig's Disease
Motor Neuron Disease
Amyotrophic Lateral Sclerosis (ALS)
Familial ALS

Neuromuscular disease
SOD1 mutation
Superoxide dismutase
SOD1 positive ALS
inherited ALS

Additional relevant MeSH terms:

Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases

Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on February 09, 2012