Baxter International has announced that its Phase III clinical study of Immunoglobulin ( IG ) did not meet its co-primary endpoints of reducing cognitive decline and preserving functional abilities in patients with mild to moderate Alzheimer's disease. The Gammaglobulin Alzheimer's Partnership ( GAP ) study was conducted by Baxter in collaboration with the Alzheimer's Disease Cooperative Study ( ADCS ), a clinical trial consortium supported by the United States National Institute on Aging in the National Institutes of Health.

The analyses from the randomized, double-blind, placebo-controlled, multi-center trial found that after 18 months of treatment, patients with mild to moderate Alzheimer's disease taking IG treatment at either the 400 mg/kg or the 200 mg/kg dose did not demonstrate a statistically significant difference in the rate of cognitive decline as compared to placebo ( mean 7.4 in the 400 mg/kg group, 8.9 in the 200 mg/kg group, and 8.4 in the placebo group ). Results also did not indicate a statistically significant change in functional ability as compared to placebo ( mean -11.4 in the 400 mg/kg group, -12.4 in the 200 mg/kg group, and -11.4 in the placebo group ).

While the study was not powered to show statistical significance among the sub-groups, in the pre-specified sub-group analysis, the 400 mg/kg treatment arm showed a positive, numerical difference in change from baseline versus placebo in cognition as measured by the Alzheimer's Disease Assessment Scale - Cognitive Subscale ( ADAS-Cog ) and Modified Mini-Mental State ( 3MS ) Examination among both moderate patients and carriers of the ApoE4 genetic marker. These differences ranged between 16 and 29%.

IG was well tolerated in the study and no new safety signals were identified associated with treatment in this patient population, ages 50-89. The most common adverse reactions ( observed in at least 5% of patients ) during treatment with IG were rash and decreases in hemoglobin. There were no differences in the rate of thromboembolic events in the treated groups versus placebo groups. There were 17 serious adverse reactions considered to be treatment-related in the study ( 12 in the IG cohorts and 5 in the placebo cohort ).

The GAP study was the largest placebo-controlled study of Immunoglobulin, and was designed to assess the safety and effectiveness of IG as a potential treatment for signs and symptoms associated with Alzheimer's disease. The clinical trial treated 390 patients with mild to moderate Alzheimer's disease across 45 Centers in the U.S. and Canada. Patients were randomized to treatment with IG treatment at either 400 mg/kg or 200 mg/kg dosing every two weeks for 18 months, or placebo. All patients were required to maintain their treatment regimen of approved medications for Alzheimer's disease symptom management.

Immunoglobulin is made from purified human plasma, which is collected from healthy volunteers. The immunoglobulin in plasma contains human antibodies that protect the body against infection, offering important immunomodulatory and anti-inflammatory properties that help treat rare immune-related and neurological conditions.
Immunoglobulin is made from human plasma and may carry a risk of transmitting infectious agents.
Immunoglobulin products have demonstrated the ability to induce severe hypersensitivity reactions, thrombotic events, hemolytic anemia and renal dysfunction, acute renal failure, osmotic nephrosis, and death in pre-disposed patients. Immunoglobulin contains blood group antibodies that may act as hemolysins.
Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IG.
Aseptic meningitis syndrome has also been reported following intravenous administration of IG.
Non-cardiogenic pulmonary edema ( TRALI ) has been reported in patients following treatment with IG products.

Source: Baxter, 2013

XagenaMedicine2013