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 Alzheimer’s type under treatment with increasing dosages of intravenous immunoglobulin (Octagam® 10%)

ISRCTN ISRCTN64846759
DOI https://doi.org/10.1186/ISRCTN64846759
ClinicalTrials.gov number NCT00812565
Secondary identifying numbers GAM10-04
Submission date
23/01/2009
Registration date
28/01/2009
Last edited
22/03/2016
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Stefan Wietek
Scientific

Oberlaaer Str. 235
Vienna
1100
Austria

Phone +43 (0)1 61032 1778
Email stefan.wietek@octapharma.com

Study information

Study designProspective multicentre double-blind randomised placebo-controlled phase II study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleProspective 24-week, double-blind, randomised, placebo-controlled, multicentre study evaluating safety and change in efficacy-related surrogate parameters in patients with dementia of the Alzheimer’s type under treatment with increasing dosages of intravenous immunoglobulin (Octagam® 10%)
Study objectivesComparison of different dosages and intervals of intravenous immunoglobulin (IVIG) treatment on surrogate parameters for Alzheimer's disease progression.
Ethics approval(s)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
Health condition(s) or problem(s) studiedAlzheimer's disease (mild to moderate)
InterventionOctagam 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Octagam®
Primary outcome measureEvaluation 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 measures1. 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 study start date01/02/2009
Completion date21/09/2010

Eligibility

Participant type(s)Patient
Age groupSenior
SexBoth
Target number of participants56 (7 patients per arm)
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment01/02/2009
Date of final enrolment21/09/2010

Locations

Countries of recruitment

  • Austria
  • Germany
  • United States of America

Study participating centre

Oberlaaer Str. 235
Vienna
1100
Austria

Sponsor information

Octapharma AG (Switzerland)
Industry

Seidenstrasse 2
Lachen
CH-8853
Switzerland

Website http://www.octapharma.com
ROR logo "ROR" https://ror.org/002k5fe57

Funders

Funder type

Industry

Octapharma AG (Switzerland)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results No No
Results article results 01/03/2013 Yes No

Editorial Notes

22/03/2016: added link to results - basic reporting.

On 10/04/2013 the overall trial end date was changed from 01/11/2009 to 21/09/2010.