Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment

• ClinicalTrials.gov Identifier: NCT00422981
• Recruitment Status: Completed
• First Posted: January 17, 2007
• Last Update Posted: October 24, 2012
• Sponsor: Allon Therapeutics
• Information provided by (Responsible Party): Allon Therapeutics

Tracking Information

• First Submitted Date: January 16, 2007
• First Posted Date: January 17, 2007
• Last Update Posted Date: October 24, 2012
• Study Start Date: January 2007
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 10, 2012): Change from baseline to Week 12 on the Composite Memory Variable [ Time Frame: 12 weeks ]
• Original Primary Outcome Measures (submitted: January 16, 2007): The primary outcome measure is the change from baseline (Day 1) to Week 12 on the Composite Memory Variable
• Change History: Complete list of historical versions of study NCT00422981 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 10, 2012)

• Changes in the Composite Memory Variable from baseline to weeks 4, 8, and 16 [ Time Frame: 16 weeks ]
• Changes in test battery individual items from baseline to endpoints (weeks 4, 8, 12, and 16). [ Time Frame: 16 weeks ]

Original Secondary Outcome Measures (submitted: January 16, 2007)

• Changes in the Composite Memory Variable from baseline to weeks 4, 8, and 16
• Changes in test battery individual items from baseline to endpoints (weeks 4, 8, 12, and 16).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment
• Official Title: A Phase 2, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Effect on Cognitive Function of AL-108 After 12 Weeks of Intranasal Administration in Subjects With Mild Cognitive Impairment
• Brief Summary: The purpose of this study is to find out if different doses of Investigational Drug are safe, tolerable, and if they have an effect on Mild Cognitive Impairment (MCI).

Detailed Description

Pre-Clinical experiments indicate the AL-108 compound has neuroprotective, cognitive protective and neurotrophic properties; therefore, the compound could be tested in a variety of human diseases. Human diseases include Cognitive impairment associated with aging or neurodegenerative diseases such as Alzheimer's Disease.

This clinical trial aims at providing the dose rationale as well as safety and tolerability information for AL-108 as evaluated after 12 weeks of intranasal administration in subjects with Mild Cognitive Impairment (MCI).

There are currently no drugs approved for the treatment of MCI nor accepted treatment or standard treatment approach.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Mild Cognitive Impairment, So Stated

Intervention

• Drug: AL-108
  5 mg QD
• Drug: AL-108
  15 mg BID
• Drug: Placebo
  Placebo

Study Arms

• Active Comparator: AL-108 5 mg
  5 mg QD
  Intervention: Drug: AL-108
• Active Comparator: AL-108 15 mg
  15 mg BID
  Intervention: Drug: AL-108
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• Publications *: Morimoto BH, Schmechel D, Hirman J, Blackwell A, Keith J, Gold M; AL-108-211 Study. A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Dement Geriatr Cogn Disord. 2013;35(5-6):325-36. doi: 10.1159/000348347. Epub 2013 Apr 13.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 10, 2012): 144
• Original Enrollment (submitted: January 16, 2007): 120
• Actual Study Completion Date: January 2008
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Is male or female, at 55-85 years of age (inclusive) at screening
• Self-reported memory complaint, corroborated by spouse or companion as appropriate.
• Wechsler Memory Scale III (WMS-III) age-adjusted Logical Memory II score ≤ 5.
• Mini-Mental State Exam (MMSE) ≥24.
• Center for Epidemiologic Studies-Depression (CES-D) score <27.
• Normal thyroid function, defined as TSH, T3 and T4 within normal limits.
• Agree not to consume alcoholic beverages within 8 hours of each study visit.
• Willing and able to sign informed consent and complete the CTB and all other tests and procedures as listed in the protocol.
• Fluently reads and speaks English.
• Female subjects must be surgically sterile or post-menopausal for at least 2 years. If <2 years post-menopausal, then a follicle stimulating hormone (FSH) ≥40 mIU/mL must be obtained.

Exclusion Criteria:

• Subjects who have any significant, untreated psychiatric illness or any CNS condition (such as schizophrenia, Parkinson's disease, stroke, etc.) that could interfere with the study evaluations or procedures or which poses an additional risk. Subjects with a history of uncomplicated depression may participate if in remission and on a stable dose of antidepressant medication for at least 2 months.
• History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
• History of alcohol or substance abuse or dependence within the past year.
• Acute infective sinusitis.
• History or presence of an abnormality of the external or internal structures of the nose or nasopharynx, except for surgical correction of the nasal septum or a "broken nose" at least 2 years previously, or surgical repair of cleft palate when <30 years of age.
• Use of medications that are known to cause frank obtundation of cognition
• Use of any approved or investigational medication for Alzheimer's Disease within 3 months of screening
• History of or current significant systemic disease judged to interfere with the study evaluations or likely to be a safety concern.
• Untreated sleep apnea or treatment for sleep apnea for <3 months.
• Abnormal clinical laboratory test results, specifically: Alanine transaminase (ALT) or aspartate transaminase (AST) >2 х the upper limit of normal (ULN),Hematology <80% the lower limit of normal, Creatinine ≥2 mg/dL and ,Other clinical laboratory values or vital signs considered clinically significant in the opinion of the Investigator.
• Treatment with any investigational drug, biologic, or device within the previous 30 days prior to screening.
• Surgery involving general anesthesia within the past 3 months or planned surgery requiring general anesthesia during the study period.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00422981
• Other Study ID Numbers: AL-108-211
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Allon Therapeutics
• Study Sponsor: Allon Therapeutics
• Collaborators: Not Provided

Investigators

• Principal Investigator: Donald E Schmechel, MD; Memory Assessment and Research Services

• PRS Account: Allon Therapeutics
• Verification Date: October 2012