Clinical Trial of Ceftriaxone in Subjects with Amyotrophic Lateral Sclerosis

Institutional Review Board, Hospital for Special Surgery

July 27, 2010

The safety of study participants is our top priority. The trial is approved and periodically reviewed by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.

Before enrolling in a clinical trial, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions! If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.

For further information, see Understanding Clinical Trials.

Principal Investigator

Dale J. Lange, M.D.

Summary

This is a double-blind, placebo controlled clinical trial of ceftriaxone in 600 subjects with
ALS. The study uses a sequential, non-stop drug development design. This design was chosen as a method to expedite drug development, while safely testing a new therapeutic agent in ALS.  This is a 3 stage study, we are currently recruiting for Stage 3 of this study which has 3 arms, 2 of which will receive active drug and the 3rd will receive placebo. 600 randomized subjects at approximately 70 centers in US and Canada will be enrolled in this study. Subjects in the STAGE 1 and 2 studies will roll-over into the larger phase, with the two active treatment groups receiving ceftriaxone. Subjects will remain in the study until 52 weeks after the last subject is randomized.

Inclusion/Exclusion Criteria

Inclusion Criteria

1. Participants with familial or sporadic ALS diagnosed as laboratory supported
   probable, probable or definite according to the World Federation of Neurology El
   Escorial criteria [142], Appendix 2
2. Age 18 years or older
3. Capable of providing informed consent and complying with trial procedures.
4. Vital capacity (VC) at least 60% predicted value for gender, height and age at
   screening
5. Women must not be able to become pregnant (e.g. post menopausal, surgically sterile,
   or using adequate birth control methods) for the duration of the study. Adequate
   contraception includes: abstinence, hormonal contraception (oral contraception,
   implanted contraception, injected contraception or other hormonal (patch or
   contraceptive ring, for example) contraception), intrauterine device (IUD) in place for
   = 3 months, barrier method in conjunction with spermicide, or another adequate
   method (as determined by steering committee member review). Women of
   childbearing potential must have a negative pregnancy test at screening and be nonlactating.
6. First ALS symptoms occurred no more than 3 years prior to screening visit
7. Not taking riluzole, or on a stable dosage for at least thirty days prior to the screening
   visit
8. Subject has a competent caregiver who can and will be responsible for administration
   of study drug. If there is no caregiver, another qualified individual must be available
   to administer the study drug.
9. Geographic accessibility to the study site
10.Subjects medically able to undergo placement of central venous catheter as
   determined by the investigator (to include absence of systemic infection, a medical
   disorder which precludes catheter placement)

Exclusion Criteria

1. Dependence on mechanical ventilation (invasive or non-invasive, including Continuous
   Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPap) for any
   part of the day or night prior to the screening visit.
2. Exposure to ceftriaxone or any cephalosporin within 30 days prior to the screening visit.
3. History of known sensitivity or intolerability to ceftriaxone or to any other cephalosporin.
4. History of known sensitivity or intolerability to penicillin or any beta lactam (including
   mild rash).
5. Exposure to any other investigational agent within 30 days prior to screening visit.
6. Known immune compromising illness or therapy
7. Active gastrointestinal disease within 30 days of the screening visit
8. History of antibiotic-induced colitis
9. Active biliary disease, including gallstones
10. Presence of any of the following clinical conditions
 a. Drug abuse or alcoholism
 b. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active
    infectious disease, including current malignancy
 c. AIDS or AIDS-related complex
 d. Unstable psychiatric illness defined as psychosis or untreated major depression
    within 90 days of the Screening Visit.
11. Laboratory values: Screening alanine aminotransferase (ALT) greater than 3.0 times the upper limit of normal or, total bilirubin greater than 1.5 times
    the upper limit of normal,absolute neutrophil count of < or 1000/ul, platelet concentration of <100,000/ul, hematocrit level of <33 for female or <35 for
    male, Or coagulation tests > 1.5 times upper limit of normal.
12. Women of childbearing potential not practicing adequate contraception
13. History of known sensitivity to bile acids or ursodiol
    Riluzole. The use of riluzole will be permitted during the study. Subjects taking riluzole must be on a stable dosage for 30 days prior to screening.|
    Subjects are not allowed to start taking riluzole during the trial.

Contact Information

Mona Shahbazi, RN, OCN, MSN
shabbazim@hss.edu
212.774.2361