Condition category
Nervous System Diseases
Date applied
23/01/2009
Date assigned
28/01/2009
Last edited
22/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 Alzheimer’s 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 measures

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

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

http://www.octapharma.com

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

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT00812565

Publication summary

2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23375965

Publication citations

  1. 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.

Additional files

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.