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%)

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 design	Prospective multicentre double-blind randomised placebo-controlled phase II study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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%)
Study objectives	Comparison 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) studied	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	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 study start date	01/02/2009
Completion date	21/09/2010

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	56 (7 patients per arm)
Key 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
Key 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
Date of first enrolment	01/02/2009
Date of final enrolment	21/09/2010

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"	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 share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not 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.

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%)