Study Evaluating Safety, Tolerability, And Immunogenicity Of ACC-001 In Subjects With Mild To Moderate Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT00479557
• Recruitment Status: Completed
• First Posted: May 28, 2007
• Results First Posted: January 1, 2016
• Last Update Posted: January 1, 2016
• Sponsor: Pfizer
• Collaborator: Janssen Alzheimer Immunotherapy (JAI) Research and Development, LLC
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 24, 2007
• First Posted Date: May 28, 2007
• Results First Submitted Date: May 6, 2014
• Results First Posted Date: January 1, 2016
• Last Update Posted Date: January 1, 2016
• Study Start Date: May 2007
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2015)

Percentage of Participants With Treatment-emergent AEs or Serious Adverse Events (SAEs) [ Time Frame: approximately 110 weeks, including a 6-week screening period, 52 weeks of dosing and 54 weeks for follow-up after the last dose. ]

An AE was any untoward, undesired, or unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study drug or in a sponsor's clinical study. The event did not need to be causally related to the study drug or the clinical studies. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

• Original Primary Outcome Measures (submitted: May 24, 2007): Adverse events and other safety assessment, tolerability, and immunogenicity. [ Time Frame: 2 years participation per patient ]

Current Secondary Outcome Measures (submitted: November 30, 2015)

• Geometric Mean Titers (GMTs) of Anti-A-beta Immunoglobulin G (IgG) Total Using an Enzyme-linked Immunosorbent Assay (ELISA) at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 ]
  The lower limit of quantification (LLOQ) was 100 U/mL and when the assay result was below LLOQ (100 U/mL), 50 U/mL was imputed for IgG.
• GMTs of Anti-A-beta Immunoglobulin M (IgM) Using ELISA at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 ]
  The LLOQ was 50 U/mL and when the assay result was below LLOQ (50 U/mL), 25 U/mL was imputed for IgM.
• Change From Baseline GMTs of Anti-A-beta IgG Subtypes Using ELISA at Visits Where an IgG Total Response is Measurable (at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 if Applicable) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 ]
  IgG subtypes were not assessed

• Original Secondary Outcome Measures (submitted: May 24, 2007): Cognitive and functional measures
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Safety, Tolerability, And Immunogenicity Of ACC-001 In Subjects With Mild To Moderate Alzheimer's Disease
• Official Title: A Phase Iia, Multicenter, Randomized, Third-party Unblinded, Adjuvant And Placebo-controlled, Multiple Ascending Dose, Safety, Tolerability And Immunogenicity Trial Of Acc-001 And Qs-21 Adjuvant In Subjects With Mild To Moderate Alzheimer's Disease
• Brief Summary: To assess the safety, tolerability, and immunogenicity of ACC-001, an investigational active immunization, in patients with mild to moderate Alzheimer's disease.
• Detailed Description: Not Provided
• 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: Alzheimer Disease

Intervention

• Biological: ACC-001 + QS-21
  Vanutide Cridificar (3, 10, 30µg) + QS-21 (50µg), IM on day 1, month 1, month 3, month 6 and month 12
• Biological: ACC-001
  Vanutide Cridificar (10, 30µg), IM on day 1, month 1, month 3, month 6 and month 12
• Biological: QS-21
  QS-21 (50µg), IM on day 1, month 1, month 3, month 6 and month 12
• Drug: Placebo: Phosphate buffered saline
  Phosphate buffered Saline (pH : 7.4), IM on day 1, month 1, month 3, month 6 and month 12

Study Arms

• Active Comparator: 1
  arm 1: ACC-001 (Vanutide Cridificar)+ QS-21
  Intervention: Biological: ACC-001 + QS-21
• Active Comparator: 2
  arm 2: ACC-001
  Intervention: Biological: ACC-001
• Placebo Comparator: 3
  arm 3: QS-21
  Intervention: Biological: QS-21
• Placebo Comparator: 4
  Drug: Phosphate Buffered Saline (PBS)
  Intervention: Drug: Placebo: Phosphate buffered saline

• Publications *: Pasquier F, Sadowsky C, Holstein A, Leterme Gle P, Peng Y, Jackson N, Fox NC, Ketter N, Liu E, Ryan JM; ACC-001 (QS-21) Study Team. Two Phase 2 Multiple Ascending-Dose Studies of Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Mild-to-Moderate Alzheimer's Disease. J Alzheimers Dis. 2016;51(4):1131-43. doi: 10.3233/JAD-150376.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 15, 2013): 86
• Original Estimated Enrollment (submitted: May 24, 2007): 56
• Actual Study Completion Date: January 2013
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of probable Alzheimer's Disease with Mini-Mental State Examination (MMSE) score of 16-26 (except Germany: 21-26)
• Brain MRI consistent with Alzheimer Disease
• Concurent use of Chloniesterase inhibitor or memantine allowed if stable
• Other inclusion criteria apply

Exclusion Criteria:

• Significant Neurological Disease other than Alzheimer's disease
• Major psychiatric disorder
• Contraindication to undergo brain MRI
• Clinically significant systemic illness
• Other exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Spain

Administrative Information

• NCT Number: NCT00479557
• Other Study ID Numbers: 3134K1-200; B2571004 ( Other Identifier: Alias Study Number ); 2006-002061-39 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Janssen Alzheimer Immunotherapy (JAI) Research and Development, LLC

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2015