Study of Octagam (Intravenous Immunoglobulin [IVIG]) 10% on the Treatment of Mild to Moderate Alzheimer's Disease

NCT ID: NCT00812565

Last Updated: 2014-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2010-09-30

Brief Summary

This study evaluated the effect of 6 or 12 infusions of different doses of octagam (intravenous immunoglobulin [IVIG]) 10% on the reduction of amyloid beta peptide (Aβ) in cerebral spinal fluid (CSF) and on the increase of Aβ in blood plasma in patients with mild to moderate Alzheimer's disease.

Detailed Description

Participants received 12 infusions of 0.1 g/kg, 0.25 g/kg, or 0.4 g/kg body weight octagam 10% at 2-week intervals (±3 days) or 6 infusions of 0.2 g/kg, 0.5 g/kg, or 0.8 g/kg body weight octagam 10% at 4-week intervals (±5 days). The effect of the infusions on the reduction of Aβ peptide in CSF and the increase of Aβ peptide in blood plasma was evaluated.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

0.4 g/kg octagam 10% every 2 weeks

Participants received of 0.4 g/kg octagam 10% every 2 weeks for 24 weeks (total of 12 infusions).

Group Type: EXPERIMENTAL

octagam 10%

Intervention Type: BIOLOGICAL

octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.

Placebo every 4 weeks

Participants received placebo intravenously every 4 weeks for 20 weeks (total of 6 infusions).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Commercially available 0.9% isotonic sodium chloride solution.

0.2 g/kg octagam 10% every 4 weeks

Participants received 0.2 g/kg octagam 10% intravenously every 4 weeks for 20 weeks (total of 6 infusions).

Group Type: EXPERIMENTAL

octagam 10%

Intervention Type: BIOLOGICAL

octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.

0.5 g/kg octagam 10% every 4 weeks

Participants received 0.5 g/kg octagam 10% every 4 weeks for 20 weeks (total of 6 infusions).

Group Type: EXPERIMENTAL

octagam 10%

Intervention Type: BIOLOGICAL

octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.

0.8 g/kg octagam 10% every 4 weeks

Participants received of 0.8 g/kg octagam 10% every 4 weeks for 20 weeks (total of 6 infusions).

Group Type: EXPERIMENTAL

octagam 10%

Intervention Type: BIOLOGICAL

octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.

Placebo every 2 weeks

Participants received placebo intravenously every 2 weeks for 24 weeks (total of 12 infusions).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Commercially available 0.9% isotonic sodium chloride solution.

0.1 g/kg octagam 10% every 2 weeks

Participants received 0.1 g/kg octagam 10% intravenously every 2 weeks for 24 weeks (total of 12 infusions).

Group Type: EXPERIMENTAL

octagam 10%

Intervention Type: BIOLOGICAL

octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.

0.25 g/kg octagam 10% every 2 weeks

Participants received 0.25 g/kg octagam 10% every 2 weeks for 24 weeks (total of 12 infusions).

Group Type: EXPERIMENTAL

octagam 10%

Intervention Type: BIOLOGICAL

octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.

Interventions

Placebo

Commercially available 0.9% isotonic sodium chloride solution.

Intervention Type: DRUG

octagam 10%

octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.

Intervention Type: BIOLOGICAL

Other Intervention Names

IVIG

Eligibility Criteria

Inclusion Criteria

• Probable Alzheimer's Disease (AD) according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
• Age of 50 to 85.
• Mini-mental State Examination (MMSE) score of 16 to 26.
• Sufficient language skills for testing.
• Sufficient vision and hearing for testing.
• Modified Hachinski-Rosen Score < 5.
• Magnetic resonance imaging (MRI) of the head consistent with the diagnosis of AD.
• Caregiver available with contact at least 4 days per week for greater than 1 hour.
• Outpatient status or assisted living.
• Post-menopause (women) as evidenced by lack of menstruation for at least 12 consecutive months or by having bilateral oophorectomy.
• Stable doses of approved AD medication(s) for at least 3 months prior to screening (eg, acetylcholine esterase (AChE) inhibitors, memantine).
• Normal vital signs or clinically insignificant, if outside normal limits.
• Laboratory findings within normal limits or clinically insignificant, if outside normal limits.
• Normal electrocardiogram (ECG) or clinically not significant, if outside normal limits.

Exclusion Criteria

• Other causes of dementia (eg, vascular dementia, Lewy-body dementia, fronto-temporal dementia, Creutzfeldt-Jacob disease, Huntington's disease, Parkinson's disease).
• History of or present significant other diseases of the central nervous system (eg, brain tumor, normal pressure hydrocephalus, Parkinson's Disease, stroke, severe brain trauma, brain surgery, epilepsy, encephalitis).
• Geriatric depression scale score > 7 (short form with scale from 0 to 15).
• Present significant psychiatric disorder (eg, major depression).
• History of psychosis or hallucinations.
• Mental retardation.
• Unstable medical disease in the opinion of the investigator.
• Insulin dependent diabetes mellitus.
• Acute infectious disease.
• Vitamin B12 deficiency unless on stable replacement therapy for at least 3 months is acceptable.
• Unstable thyroid dysfunction.
• Uncontrolled hypertension.
• Severe liver or kidney disease.
• Major surgery within 3 months prior to screening.
• Prohibited medications: Antiepileptic drugs, antipsychotics (but allowed for treatment of acute episodes), antiparkinson agents, anticholinergic drugs, selegiline, monoamine oxidase inhibitors (MAOI), tricyclics, immunosuppressive medications, anti-histamines (unless on a stable dose for at least 3 months or used for treatment of acute episodes), benzodiazepines (but allowed for treatment of acute episodes), and lithium.
• Antidepressants are permitted, if on a stable dose for at least 3 months and without significant anticholinergic side-effects.
• Peripheral venous conditions which impair establishing regular venous access for infusions.
• Potential reasons that patient may become non-evaluable during the study (eg, planned moving into a nursing home, but assisted living is acceptable).
• Peripheral venous conditions, which impair establishing regular venous access for infusions.
• Known IgA deficiency with antibodies to IgA.
• History of hypersensitivity to blood or plasma derived products, or any component of octagam 10%, such as maltose.
• Medical conditions which interfere with protein catabolism (eg, nephrotic syndrome).
• Known blood hyperviscosity or other hypercoagulable states.
• Deep vein thrombosis within preceding 4 years.
• Symptomatic stroke.
• Transient ischemic attack (TIA) within preceding 2 years.
• Participation in another drug trial within the previous 3 months before screening.
• Participation in immunological treatment studies of AD other than with intravenous immunoglobulin (IGIV) within the previous 6 months before screening.
• IGIV use in the previous 6 months.
• Live viral vaccination within the last month before study entry.
• Not eligible for lumbar puncture (anticoagulant therapy, coagulation disorders, severe spinal alterations).
• Patients with a past or present history of drug abuse or alcohol abuse within the preceding 5 years.
• Patients with any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Octapharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wolfgang Frenzel, MD

Role: STUDY_DIRECTOR

Octapharma Pharmazeutika Produktionsges.m.b.H., Vienna, Austria

Locations

Octapharma USA

Hoboken, New Jersey, United States

Countries

United States

References

Dodel R, Rominger A, Bartenstein P, Barkhof F, Blennow K, Forster 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 Mar;12(3):233-43. doi: 10.1016/S1474-4422(13)70014-0. Epub 2013 Jan 31.

Reference Type: DERIVED

PMID: 23375965 (View on PubMed)

Other Identifiers

GAM10-04

Identifier Type: -

Identifier Source: org_study_id