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

NCT00812565 | Completed Phase 2 Results DMC

• 1 other identifier: GAM10-04
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Change in the Area Under the Curve of Plasma Aβ1-40 in the 2 or 4 Weeks After the Last Treatment Infusion From the Trough Level Prior to the Last Treatment Infusion

  For participants who received infusions every 2 weeks, plasma samples were collected at the trough level at Week 22 and on Days 1, 4, 7, and 14 after Week 22. For participants who received infusions every 4 weeks, plasma samples were collected at the trough level at Week 20 and on Days 1, 4, 7, 14, 21, and 28 after Week 20. Samples for determining Aβ1-40 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium).

  Week 22 to Week 24 for participants who received infusions every 2 weeks and Week 20 to Week 24 participants who received infusions every 4 weeks

Secondary Outcomes (13)

• Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24)

  Baseline to Week 24

• Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24)

  Baseline to Week 24

• Change in the Area Under the Curve of Plasma Aβ1-42 in the 2 or 4 Weeks After the Last Treatment Infusion From the Trough Level Prior to the Last Treatment Infusion

  Week 22 to Week 24 for participants who received infusions every 2 weeks and Week 20 to Week 24 participants who received infusions every 4 weeks

• Change in the Area Under the Curve of Plasma Anti-Aβ Autoantibodies in the 2 or 4 Weeks After the Last Treatment Infusion From the Trough Level Prior to the Last Treatment Infusion

  Week 22 to Week 24 for participants who received infusions every 2 weeks and Week 20 to Week 24 participants who received infusions every 4 weeks

• Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion

  Baseline to Week 23 Day 2 for participants who received infusions every 2 weeks and Baseline to Week 21 Day 2 for participants who received infusions every 4 weeks

Study Arms (8)

Placebo every 2 weeks

PLACEBO COMPARATOR

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

Drug: Placebo

0.1 g/kg octagam 10% every 2 weeks

EXPERIMENTAL

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

Biological: octagam 10%

0.25 g/kg octagam 10% every 2 weeks

EXPERIMENTAL

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

Biological: octagam 10%

0.4 g/kg octagam 10% every 2 weeks

EXPERIMENTAL

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

Biological: octagam 10%

Placebo every 4 weeks

PLACEBO COMPARATOR

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

Drug: Placebo

0.2 g/kg octagam 10% every 4 weeks

EXPERIMENTAL

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

Biological: octagam 10%

0.5 g/kg octagam 10% every 4 weeks

EXPERIMENTAL

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

Biological: octagam 10%

0.8 g/kg octagam 10% every 4 weeks

EXPERIMENTAL

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

Biological: octagam 10%

Interventions

Placebo DRUG

Commercially available 0.9% isotonic sodium chloride solution.

Placebo every 2 weeks; Placebo every 4 weeks

octagam 10% BIOLOGICAL

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

Also known as: IVIG

0.1 g/kg octagam 10% every 2 weeks; 0.2 g/kg octagam 10% every 4 weeks; 0.25 g/kg octagam 10% every 2 weeks; 0.4 g/kg octagam 10% every 2 weeks; 0.5 g/kg octagam 10% every 4 weeks; 0.8 g/kg octagam 10% every 4 weeks

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Octapharma: lead

Study Sites (1)

Octapharma USA

Hoboken, New Jersey, United States

Location

Related Publications (1)

• 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.

  PMID: 23375965 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Small numbers of patients per treatment group (between 5 and 8) and variable total Aβ levels over time.

Results Point of Contact

• Title: Michael Eppolito, Director, Clinical Operations Immunology and ICU Medicine
• Organization: Octapharma USA

michael.eppolito@octapharma.com

201-604-1155

Study Officials

• Wolfgang Frenzel, MD

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2008
• First Posted: December 22, 2008
• Study Start: February 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: May 5, 2014
• Results First Posted: May 5, 2014

Record last verified: 2014-04

Locations

US (1)