Contact information
Type
Scientific
Primary contact
Dr Stefan Wietek
ORCID ID
Contact details
Oberlaaer Str. 235
Vienna
1100
Austria
+43 (0)1 61032 1778
stefan.wietek@octapharma.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00812565
Protocol/serial number
GAM10-04
Study information
Scientific title
Prospective 24-week, double-blind, randomised, placebo-controlled, multicentre study evaluating safety and change in efficacy-related surrogate parameters in patients with dementia of the Alzheimers type under treatment with increasing dosages of intravenous immunoglobulin (Octagam® 10%)
Acronym
Study hypothesis
Comparison of different dosages and intervals of intravenous immunoglobulin (IVIG) treatment on surrogate parameters for Alzheimer's disease progression.
Ethics approval
1. Central Ethics Committee EC Marburg (Germany)
2. Local Institutional Review Boards (IRBs) of three Unites States of America (USA) sites; approval of protocol amendment no. 2 by IUPUI/Clarian IRB (Indianapolis, USA), 08/01/2009, ref: 0811-07
Study design
Prospective multicentre double-blind randomised placebo-controlled phase II study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Alzheimer's disease (mild to moderate)
Intervention
Octagam 10% (12 infusions of 0.1 g/kg, 0.25 g/kg or 0.4 g/kg every 2 weeks or 6 infusions of 0.2 g/kg, 0.5 g/kg or 0.8 g/kg every 4 weeks) or matching placebo.
Blood samples will be drawn before each infusion and at day 1, 4, 7, 14, 21 and 28 (the latter two only for patients on 4-week interval) after last infusion. Lumbar puncture will be performed at baseline and 1 day after last infusion, MRI at screening, week 12 and 24 and 18-fluoro-2-deoxy-glucose-positron emission tomography (FDG-PET) scans at baseline and week 24.
Intervention type
Drug
Phase
Phase II
Drug names
Octagam®
Primary outcome measure
Evaluation of the decrease of total amyloid beta in the central nervous system (CNS) and the increase in blood plasma after 24 weeks (area under curve [AUC] of total amyloid beta [Abeta] concentration in plasma).
Secondary outcome measures
1. Further characterisation of the decrease of amyloid beta in the cerebrospinal fluid (CSF) and the increase in blood plasma by measuring an additional surrogate parameter (biomarker, Ab1-42), by assessing the changes in the biomarker proteins Tau and phosphorylated Tau (pTau 181) after 6 months of treatment and of the anti-Ab autoantibodies during the 6-month treatment period
2. Change in Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog), MMSE, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and Clinical Dementia Rating Sum of Boxes (CDR-SOB) at week 12 and 24 compared to baseline
3. Change in whole brain and hippocampal volume on volumetric MRI at week 12 and 24 compared to screening
4. Change in cerebral glucose metabolism determined by FDG-PET at week 24 compared to baseline
Overall trial start date
01/02/2009
Overall trial end date
21/09/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Probable Alzheimer's disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
2. Written informed consent by patient or, for significantly cognitively impaired individuals, their legally authorised representative
3. Aged greater than or equal to 50 and less than or equal to 85 years, either sex
4. Mini-mental State Examination (MMSE) greater than or equal to 16 and less than or equal to 26
5. Only for Germany: the patient's capacity to consent has to be confirmed by dated signature on the informed consent form by a second independent investigator who is otherwise not involved in study GAM10-04
6. Modified Hachinski-Rosen Score less than 5
7. Magnetic resonance imaging (MRI) of the head consistent with the diagnosis of AD
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
56 (7 patients per arm)
Participant exclusion criteria
1. Other causes of dementia (e.g. vascular dementia, Lewy Body dementia, fronto-temporal dementia, Creutzfeld-Jacob disease, Huntington's disease, Parkinson's disease)
2. History of or present significant other diseases of the central nervous system (e.g. brain tumour, normal pressure hydrocephalus, stroke, severe brain trauma, brain surgery, epilepsy, encephalitis)
3. Geriatric depression scale of greater than 7 (short form with scale from 0 to 15)
4. Present significant psychiatric disorder (e.g. major depression)
5. History of psychosis or hallucinations
6. Mental retardation
7. Unstable medical disease in the opinion of the investigator
8. Insulin dependent diabetes mellitus
9. Acute infectious disease
10. Uncontrolled hypertension (diastolic blood pressure [BP] greater than 90 mmHg or systolic BP greater than 160 mmHg; sitting)
11. Symptomatic stroke
12. Transient ischaemic attack (TIA) within preceding 2 years
13. Participation in other drug trial currently or within the previous 3 months before screening
Recruitment start date
01/02/2009
Recruitment end date
21/09/2010
Locations
Countries of recruitment
Germany, United States of America
Trial participating centre
Oberlaaer Str. 235
Vienna
1100
Austria
Sponsor information
Organisation
Octapharma AG (Switzerland)
Sponsor details
Seidenstrasse 2
Lachen
CH-8853
Switzerland
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Octapharma AG (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00812565
Publication list
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23375965
Publication citations
-
Results
Dodel R, Rominger A, Bartenstein P, Barkhof F, Blennow K, Förster S, Winter Y, Bach JP, Popp J, Alferink J, Wiltfang J, Buerger K, Otto M, Antuono P, Jacoby M, Richter R, Stevens J, Melamed I, Goldstein J, Haag S, Wietek S, Farlow M, Jessen F, Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial., Lancet Neurol, 2013, 12, 3, 233-243, doi: 10.1016/S1474-4422(13)70014-0.