Effect of Passive Immunization on the Progression of Alzheimer’s Disease: LY2062430 versus Placebo

• Register: EUCTR
• Last refreshed on: 16 September 2013
• Main ID: EUCTR2008-007926-21-DE
• Date of registration: 13/03/2009
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: Effect of Passive Immunization on the Progression of Alzheimer’s Disease: LY2062430 versus Placebo
• Scientific title: Effect of Passive Immunization on the Progression of Alzheimer’s Disease: LY2062430 versus Placebo
• Date of first enrolment: 05/08/2009
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007926-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

France, Germany, Italy, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1.Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD (McKhann et al. 1984; Protocol Attachment LZAN.3) as determined by a neurologist or geriatrician.
2.Has a Modified Hachinski Ischemia Scale (MHIS; Hachinski et al. 1975; Protocol Attachment LZAN.3) score of =4.
3.Has a Folstein MMSE score of 16 through 26 at Visit 1 (Folstein et al. 1975; Protocol Attachment LZAN.3).
4.Has a Geriatric Depression Scale (GDS) score of =6 (on the staff-administered short form).
5.Has had an MRI or computerized tomography (CT) scan performed within the past 2 years that has confirmed no findings inconsistent with a diagnosis of AD. Results of this MRI or CT are to be on file at the site. If a patient has not had a prestudy MRI/CT scan in the past 2 years or attempts to obtain offsite imaging results are unsuccessful, then a screening non-contrast head CT is to be performed; due diligence to obtain offsite results should be documented in the patient’s file before obtaining a screening non-contrast head CT scan or MRI scan. Alternatively, the MRI scan required prior to solanezumab administration at Visit 2 may be used to assess eligibility upon approval by the Medical Monitor.
6.Is at least 55 years old, and if a female of childbearing potential, tests negative for pregnancy at Visit 1 and is using a medically accepted means of contraception.
7.If receiving concurrent treatment with an AChEI and/or memantine, has been on the medication for at least 4 months with a stable dose for at least 2 months before Visit 2. Dosing must remain stable throughout the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
[8] Does not have a reliable caregiver who is in frequent contact with the patient (defined as at least 10 hours per week), will accompany the patient to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications.
Note: The caregiver(s) must be able to communicate with site personnel and be willing to comply with protocol requirements, and in the investigator’s opinion must have adequate literacy to complete the protocol-specified questionnaires. Participants living in an assisted-living facility may be included if study medication intake is supervised and if regular contact with a caregiver who accompanies the patient is maintained. If it is known that the caregiver could change and the two caregivers are available (in the same location) both should be advised of the study procedures and may attend the visits with the patient. In addition, both will have to sign the Informed Consent Document (ICD) (see section 13.1).
[9] Meets National Institute of Neurological Disorders and Stroke/ Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia (detailed in Protocol Attachment LZAN(a).3).
[10] Does not have good venous access, such that intravenous drug delivery or multiple blood draws would be precluded.
[11] Has current serious or unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator’s opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <2 years.
[12] Has had multiple episodes of head trauma, or a history within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis) or head trauma resulting in protracted loss of consciousness.
Solanezumab H8A-MC-LZAN(a) Protocol Amendment
Confidential
[13] Has a history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate specific antigen (PSA) posttreatment.
[14] Has allergies to humanized monoclonal antibodies.
[15] Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis).
[16] Has a history of chronic alcohol or drug abuse/dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) within the past 5 years.
[17] Is clinically judged by the investigator to be at serious risk for suicide.
[18] Has a recent (within 6 months before screening) or current laboratory result (if available) indicating a clinically significant laboratory abnormality as determined by the investigator.
[19] Has ECG abnormalities obtained at Visit 1 that, in the opinion of the investigator, are clinically significant with regard to the patient’s participation in the study. Bazett’s corrected QT [QTcB] interval must be evaluated and must not exceed >458 msec in males or >474 msec in females.
[20

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer’s Disease
MedDRA version: 14.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Solanezumab
Product Code: LY2062430
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Solanezumab
Current Sponsor code: LY2062430
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: The primary objective of this study is to test the hypothesis that intravenous infusion of LY2062430 will slow the decline of AD as compared with placebo, as assessed at 80 weeks after initiation of treatment using a mixed-model repeated-measures (MMRM) analysis of 2 coprimary outcomes, the 11 item Alzheimer’s Disease Assessment Scale—Cognitive subscore (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study—Activities of Daily Living Inventory (ADCS-ADL). The specific hypothesis is that the change at the end of the treatment phase for LY2062430 will be significantly less than that for placebo.

Primary end point(s): Each of the 2 coprimary endpoints, ADAS-Cog11 and the ADCS-ADL, will be analyzed separately using an MMRM analysis. The change from baseline score at each visit postbaseline during the treatment period will be the dependent variable. The model for the fixed effects will include 8 terms: baseline score, investigator, treatment, MMSE stratification factor at baseline (mild or moderate), visit, treatment-by-visit interaction, concomitant AChEI or memantine use at baseline (yes/no), and age at baseline. Visit will be considered a categorical variable with values equal to the visit numbers at which the scales were assessed. The null hypothesis is that the contrast between the LY2062430 group versus placebo at the last visit equals zero. A rejection of the null hypothesis in favor of the alternative, showing that LY2062430 is superior to placebo, will demonstrate a treatment effect

Secondary Objective: To assess global clinical benefit of treatment as demonstrated through CDR-SB and NPI
To provide supporting evidence that LY2062430 attenuates the underlying pathologic process in AD by vMRI to assess the rate of decline in brain volumes
To compare the safety of LY2062430 and placebo
To characterize population pharmacokinetics
To test the hypothesis that LY2062430 will slow the rate of decline associated with AD compared with placebo using ADAS-Cog11, ADCS-ADL, ADAS-Cog12, ADAS-Cog14 and MMSE
To assess clinical benefit of treatment with LY2062430 as demonstrated through RUD-Lite, EQ-5D Proxy, and QoL-AD scale
To assess differential rate of functional decline with LY2062430 compared with placebo using a subset of items from the ADCS-ADL for instrumental ADLs
To provide further supporting evidence that LY2062430 attenuates the underlying pathologic process in AD as measured by several additional biomarkers that will be collected via optional study addenda

Secondary ID(s)

H8A-MC-LZAN(b)