This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Octagam (Intravenous Immunoglobulin [IVIG]) 10% on the Treatment of Mild to Moderate Alzheimer's Disease (NCT00812565), a randomized phase 2 study. The primary outcome is 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.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00812565 |
| Phase | Phase 2 |
| Condition | Alzheimer's Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 58 |
| Arms in the primary outcome | 8 |
| Lead sponsor | Octapharma |
| Results posted | Yes |
2. Clinical Question
Population
People with mild to moderate Alzheimer’s disease. The primary endpoint analysis population was the full analysis set: randomized participants who received at least one infusion and had at least one post-baseline efficacy assessment. The registry says only participants with available data were included in that analysis.
Intervention
Octagam 10%, an intravenous immunoglobulin, administered in different doses and schedules. The every-2-weeks groups received 0.1 g/kg, 0.25 g/kg, or 0.4 g/kg for 24 weeks. The every-4-weeks groups received 0.2 g/kg, 0.5 g/kg, or 0.8 g/kg for 20 weeks.
Comparator
Intravenous placebo, administered every 2 weeks for 24 weeks or every 4 weeks for 20 weeks. Both schedules were represented in the randomized parallel-group study.
Primary question
How did plasma Aβ1-40 area under the curve change during the period after the last infusion, relative to the trough level before that infusion? The registry reports arm-level means and standard deviations. It does not report an estimable two-arm comparison for this continuous endpoint.
The primary measure was a biological surrogate rather than a direct measure of daily function or clinical progression. Secondary outcomes included plasma and cerebrospinal-fluid measures of amyloid beta and anti-Aβ autoantibodies, cerebrospinal-fluid tau measures, and change in Mini Mental Status Examination score. These outcomes give context to the range of biological and clinical measures assessed, but the posted primary results alone do not answer whether treatment changes patients’ clinical course.
3. Trial Design
This completed phase 2 trial, NCT00812565, was a randomized, quadruple-masked, parallel-group study sponsored by Octapharma. The registry lists enrollment of 58 participants. The study began in 2009-02, and primary completion was recorded as 2010-09. Its official title describes a prospective 24-week, double-blind, randomized, placebo-controlled, multicenter study evaluating safety and efficacy-related surrogate parameters in dementia of the Alzheimer’s type.
Participants were assigned among eight groups: placebo or one of three Octagam 10% doses given every 2 weeks, and placebo or one of three doses given every 4 weeks. The every-2-weeks regimens lasted 24 weeks and involved 12 infusions. The every-4-weeks regimens lasted 20 weeks and involved 6 infusions. Thus, both dose and infusion schedule varied across the active-treatment groups, while placebo groups matched the respective schedules.
The primary endpoint was measured over different periods according to schedule. For participants receiving infusions every 2 weeks, the area-under-the-curve period was Week 22 to Week 24. For those receiving infusions every 4 weeks, it was Week 20 to Week 24. The registry describes collection of plasma samples at a trough level before the final infusion period and at specified days afterward. These schedule-specific windows matter when reading the endpoint: results from the two schedules do not represent measurements over identical post-infusion intervals.
Although the study enrolled 58 participants, the primary endpoint summaries include only the participants with available data in the analysis population. The number analyzed in each primary-result arm ranges from 5.0 to 8.0. The registry record does not report a reason for every difference between enrollment and the endpoint-specific arm counts.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Qualified patients meeting all inclusion exclusion criteria and providing informed consent were enrolled into the trial.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | Placebo Every 2 Weeks | 0.1 g/kg Octagam 10% Every 2 Weeks | 0.25 g/kg Octagam 10% Every 2 Weeks | 0.4 g/kg Octagam 10% Every 2 Weeks | Placebo Every 4 Weeks | 0.2 g/kg Octagam 10% Every 4 Weeks |
|---|---|---|---|---|---|---|
| STARTED | 8 | 7 | 7 | 7 | 7 | 7 |
| COMPLETED | 5 | 6 | 7 | 5 | 6 | 6 |
| NOT COMPLETED | 3 | 1 | 0 | 2 | 1 | 1 |
Reasons for not completing this period:
| Reason | Placebo Every 2 Weeks | 0.1 g/kg Octagam 10% Every 2 Weeks | 0.25 g/kg Octagam 10% Every 2 Weeks | 0.4 g/kg Octagam 10% Every 2 Weeks | Placebo Every 4 Weeks | 0.2 g/kg Octagam 10% Every 4 Weeks |
|---|---|---|---|---|---|---|
| Did Not Receive Study Medication | 1 | 1 | 0 | 0 | 0 | 0 |
| Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 |
| Did Not Come to Study Visit | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrawal of Consent | 1 | 0 | 0 | 0 | 1 | 0 |
| Reason Not Specified | 0 | 0 | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Full analysis set: All randomized patients who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment.
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | Placebo Every 2 Weeks | 0.1 g/kg Octagam 10% Every 2 Weeks | 0.25 g/kg Octagam 10% Every 2 Weeks | 0.4 g/kg Octagam 10% Every 2 Weeks | Placebo Every 4 Weeks | 0.2 g/kg Octagam 10% Every 4 Weeks |
|---|---|---|---|---|---|---|---|
| Participants analysed | 7 | 6 | 7 | 7 | 7 | 6 | |
| Age, Continuous | Years | 72.6 (SD 9.2) | 66.8 (SD 5.5) | 68.3 (SD 4.2) | 72.9 (SD 5.0) | 71.4 (SD 11.8) | 74.8 (SD 5.5) |
| Sex: Female, Male: Female | Participants | 4 | 1 | 3 | 3 | 5 | 2 |
| Sex: Female, Male: Male | Participants | 3 | 5 | 4 | 4 | 2 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as 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, measured over 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.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | (pg/mL)*days |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change in the area under the curve of plasma Aβ1-40 after the last treatment infusion, measured from the trough level before that infusion. Aβ1-40 is an amyloid-beta measure, and the trial’s stated aim included assessing changes in amyloid-beta measures in blood plasma and cerebrospinal fluid. The endpoint is expressed in (pg/mL)*days and summarized as a mean with a standard deviation.
The area under a concentration-time curve combines measurements taken across a specified period, rather than relying on a single blood sample. In general, this can describe the pattern of a measured substance over time during that interval. Here, the interval differed by schedule: Week 22 to Week 24 for the every-2-weeks groups and Week 20 to Week 24 for the every-4-weeks groups. Sample collection included the trough level and scheduled measurements after the relevant reference week.
The measure was used as an efficacy-related surrogate parameter. A surrogate is a biological or laboratory measure used to study a process related to a condition; it is not automatically equivalent to a clinical outcome experienced by a participant. The registry also lists outcomes such as Mini Mental Status Examination score, but that was a secondary outcome, not the primary endpoint.
The posted means describe each arm’s observed endpoint values. They do not, by themselves, establish a treatment effect relative to placebo. The registry does not report an estimable two-arm comparison for this continuous endpoint, nor does it provide confidence intervals for these arm summaries.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary results are arm-level means and standard deviations for the change in plasma Aβ1-40 area under the curve. The placebo-every-2-weeks arm had a mean of 161.2 (pg/mL)*days, with a standard deviation of 93.9 and 5.0 participants in the endpoint summary. The 0.1 g/kg, 0.25 g/kg, and 0.4 g/kg every-2-weeks arms had means of -245.7, -122.5, and -39.1, with standard deviations of 747.6, 478.3, and 172.7, respectively. Their endpoint counts were 6.0, 7.0, and 5.0.
For the every-4-weeks schedule, the placebo arm mean was 510.9, with a standard deviation of 2396.0 and 6.0 participants. The 0.2 g/kg, 0.5 g/kg, and 0.8 g/kg arms had means of -83.67, -755.4, and -262.9, with standard deviations of 957.7, 2233.0, and 671.4, respectively. Their endpoint counts were 6.0, 8.0, and 6.0. All means and standard deviations use the endpoint’s reported unit.
These summaries vary in both direction and magnitude across arms. The standard deviations are substantial relative to several means, indicating considerable spread in the observed values within those groups. With endpoint counts ranging from 5.0 to 8.0, each arm summary is based on a small number of observations. The reported summaries therefore provide limited precision about the underlying arm means, and they cannot establish whether differences between arms reflect a reproducible treatment contrast.
The record indicates that values were missing or not estimable for a two-arm comparison of this continuous endpoint. It consequently does not provide an inferential comparison of each dose group with its schedule-matched placebo. No p-value or confidence interval for such comparisons is reported in the registry record. The arm-level means should not be treated as if they were adjusted comparisons, or as evidence that any dose was better or worse than placebo.
Schedule is another important interpretive feature. The every-2-weeks and every-4-weeks groups had different treatment durations and different windows for measuring the post-infusion area under the curve. A direct comparison across schedules would therefore mix dose, schedule, and measurement-window differences. The registry presents the groups separately, and the posted results do not supply an analysis that disentangles those factors.
Overall, the primary results describe observed biological measurements in small endpoint groups. They do not establish a treatment effect, a dose-response pattern, or a clinical benefit. The result should be read as descriptive arm-level evidence with substantial uncertainty and without a reported two-arm statistical test.
9. Statistical Methods Explained
What does a mean summarize?
The primary endpoint is continuous, so the registry reports a mean for each treatment arm. In general, a mean is the arithmetic average of the observed measurements in a group. It gives a compact description of the group’s central value, but it does not show the full distribution of participants’ measurements. The mean is particularly sensitive to unusually large or small observations, which can matter when groups are small or values are widely dispersed.
The reported standard deviation describes variation among the observed values within an arm. In general, a larger standard deviation means that individual measurements are more spread out around the arm mean. It is not the same as a confidence interval and does not directly quantify uncertainty in the treatment-versus-placebo effect. The registry reports no confidence intervals for the primary endpoint means.
Why are arm summaries not a treatment comparison?
A randomized trial’s treatment question is usually answered by comparing outcomes between assigned groups, with a defined statistical analysis. A mean in one arm and a mean in another arm are descriptive summaries. Their visual or numerical separation alone does not account for sampling uncertainty, missing measurements, or any adjustment specified in an analysis plan. A treatment comparison would ordinarily report an estimated contrast and its uncertainty, and may also report a statistical test.
For this endpoint, the registry record marks the two-arm continuous comparison as having values missing or not estimable. It does not post an inferential result that can be used to assess a dose group against its schedule-matched placebo. The listed means and standard deviations can still describe the observed data, but they should not be substituted for a formal comparison. The statistical analysis plan, including any planned model or covariate adjustment, is not reported in the registry record.
What does the area-under-the-curve measure represent?
In general, area under the curve summarizes measurements across time and reflects both the measured concentration and how it changes over the specified interval. The endpoint uses plasma Aβ1-40 samples collected after the last infusion, referenced to a trough level before that infusion. The registry describes sampling at the trough and at specified days afterward. Because the sampling windows differ between the infusion schedules, the areas summarize different post-infusion intervals. This should be kept in mind when considering results across schedules.
The unit, (pg/mL)*days, expresses a concentration-time quantity. The endpoint is a laboratory measure, not a direct clinical outcome. Its interpretation as a surrogate does not establish that a change in the measure predicts a change in symptoms or function; such validation is not reported in the registry record.
Why does dispersion matter?
General statistical principle: when participant measurements vary substantially, the mean is estimated less precisely, especially when the group is small. Greater uncertainty makes it harder to distinguish an actual group difference from random variation. This trial’s arm-specific standard deviations and endpoint counts should therefore be considered together. The standard deviation describes observed spread; it is not itself a test of whether a treatment effect exists.
Over-dispersion is a general concern when observed variability exceeds what an analysis model assumes. If a model assumes less variability than the data contain, uncertainty estimates can be too small and inferential results can be misleading. The registry record does not identify an analysis model or report an over-dispersion assessment for this endpoint, so no conclusion about whether that issue arose in the trial can be made.
How should planning illustrations be read?
Any sample-size calculations based on an observed effect are planning illustrations, not observed power and not a reconstruction of the trial’s original design. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such calculations explore how an assumed effect and variability relate to a future study’s planned size. They do not show the probability that this completed trial detected an effect, and they do not demonstrate that the observed results are reliable.
The registry record does not report the trial’s own sample-size justification, planned interim analyses, or detailed statistical analysis plan. The planning assumptions should therefore be kept separate from the study’s actual design decisions and from its observed results.
10. Confidence Intervals for Each Arm
No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| Placebo Every 2 Weeks | 5 | 161.200 | 93.900 | 44.608 to 277.792 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | 6 | -245.670 | 747.580 | -1030.207 to 538.867 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | 7 | -122.500 | 478.310 | -564.863 to 319.863 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | 5 | -39.100 | 172.720 | -253.560 to 175.360 |
| Placebo Every 4 Weeks | 6 | 510.920 | 2395.800 | -2003.318 to 3025.158 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | 6 | -83.670 | 957.690 | -1088.704 to 921.364 |
R code and output
arm <- c("Placebo Every 2 Weeks", "0.1 g/kg Octagam 10% Every 2 Weeks", "0.25 g/kg Octagam 10% Every 2 Weeks", "0.4 g/kg Octagam 10% Every 2 Weeks", "Placebo Every 4 Weeks", "0.2 g/kg Octagam 10% Every 4 Weeks")
n <- c(5, 6, 7, 5, 6, 6)
m <- c(161.2, -245.67, -122.5, -39.1, 510.92, -83.67)
sp <- c(93.9, 747.58, 478.31, 172.72, 2395.8, 957.69)
sd <- sp # posted standard deviations
for (i in seq_along(n)) {
se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}
CARM Placebo Every 2 Weeks 5 161.200 93.900 44.608 277.792
CARM 0.1 g/kg Octagam 10% Every 2 Weeks 6 -245.670 747.580 -1030.207 538.867
CARM 0.25 g/kg Octagam 10% Every 2 Weeks 7 -122.500 478.310 -564.863 319.863
CARM 0.4 g/kg Octagam 10% Every 2 Weeks 5 -39.100 172.720 -253.560 175.360
CARM Placebo Every 4 Weeks 6 510.920 2395.800 -2003.318 3025.158
CARM 0.2 g/kg Octagam 10% Every 4 Weeks 6 -83.670 957.690 -1088.704 921.36411. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures and 13 posted secondary outcomes. The primary endpoint concerns plasma Aβ1-40 area under the curve; the secondary outcomes cover other plasma and cerebrospinal-fluid amyloid measures, anti-Aβ autoantibodies, tau and phosphorylated tau, and Mini Mental Status Examination score. When many outcomes are assessed, the chance of obtaining apparently notable results through chance can increase. General statistical practice may address this with prespecified outcome hierarchies or multiplicity adjustments, but whether either was used in this study is not reported in the registry record.
The registry does not report an estimable two-arm comparison for the continuous primary endpoint. It also does not post analyses for the outcomes in a way that permits a detailed account of the inferential testing strategy. Any adjustment for multiple comparisons, the ordering of hypotheses, and the handling of repeated measures are not reported in the registry record. Without those details, the results cannot be interpreted as a complete confirmatory testing program.
For the primary endpoint, the stated analysis population included randomized participants who received at least one infusion and had at least one post-baseline efficacy assessment. Only participants with available data were included in the analysis. This definition is narrower than simply describing every randomized participant, and the endpoint counts differ across arms. The registry record does not report the reasons for all unavailable observations or how missing endpoint values were handled beyond inclusion of participants with available data.
There is no information in the registry record about imputation, sensitivity analyses for missing data, or the assumptions used to address missingness. It also does not report whether the analysis followed a separate intention-to-treat definition. These omissions limit assessment of how missing observations may have influenced the reported arm summaries.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo Every 2 Weeks | 2 | 7 | 28.6% |
| 0.1 g/kg Octagam 10% Every 2 Weeks | 1 | 6 | 16.7% |
| 0.25 g/kg Octagam 10% Every 2 Weeks | 0 | 7 | 0.0% |
| 0.4 g/kg Octagam 10% Every 2 Weeks | 2 | 7 | 28.6% |
| Placebo Every 4 Weeks | 2 | 7 | 28.6% |
| 0.2 g/kg Octagam 10% Every 4 Weeks | 0 | 7 | 0.0% |
| 0.5 g/kg Octagam 10% Every 4 Weeks | 1 | 8 | 12.5% |
| 0.8 g/kg Octagam 10% Every 4 Weeks | 0 | 7 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo Every 2 Weeks | 5 of 7 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | 4 of 6 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | 5 of 7 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | 3 of 7 |
| Placebo Every 4 Weeks | 3 of 7 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | 4 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo Every 2 Weeks | 0.1 g/kg Octagam 10% Every 2 Weeks | 0.25 g/kg Octagam 10% Every 2 Weeks | 0.4 g/kg Octagam 10% Every 2 Weeks | Placebo Every 4 Weeks | 0.2 g/kg Octagam 10% Every 4 Weeks |
|---|---|---|---|---|---|---|---|
| Gastral antral vascular ectasia | Gastrointestinal disorders | 1 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Nausea | Gastrointestinal disorders | 0 of 7 | 0 of 6 | 0 of 7 | 1 of 7 | 0 of 7 | 0 of 7 |
| Vomiting | Gastrointestinal disorders | 0 of 7 | 0 of 6 | 0 of 7 | 1 of 7 | 0 of 7 | 0 of 7 |
| Knee arthroplasty | Surgical and medical procedures | 1 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Spinal laminectomy | Surgical and medical procedures | 0 of 7 | 1 of 6 | 0 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Cerebral infarction | Nervous system disorders | 0 of 7 | 0 of 6 | 0 of 7 | 1 of 7 | 0 of 7 | 0 of 7 |
| Delirium | Psychiatric disorders | 0 of 7 | 1 of 6 | 0 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Convulsion | Nervous system disorders | 0 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 1 of 7 | 0 of 7 |
| Aggression | Psychiatric disorders | 0 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 1 of 7 | 0 of 7 |
| Dementia Alzheimer's Type | Nervous system disorders | 0 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo Every 2 Weeks | 0.1 g/kg Octagam 10% Every 2 Weeks | 0.25 g/kg Octagam 10% Every 2 Weeks | 0.4 g/kg Octagam 10% Every 2 Weeks | Placebo Every 4 Weeks | 0.2 g/kg Octagam 10% Every 4 Weeks |
|---|---|---|---|---|---|---|---|
| Cerebral haemorrhage | Nervous system disorders | 0 of 7 | 2 of 6 | 1 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Headache | Nervous system disorders | 1 of 7 | 0 of 6 | 1 of 7 | 0 of 7 | 0 of 7 | 1 of 7 |
| Influenza like illness | General disorders | 0 of 7 | 0 of 6 | 2 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Bronchitis | Infections and infestations | 0 of 7 | 0 of 6 | 1 of 7 | 0 of 7 | 0 of 7 | 1 of 7 |
| Dizziness | Nervous system disorders | 1 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 1 of 7 | 0 of 7 |
| Confusional state | Psychiatric disorders | 0 of 7 | 1 of 6 | 0 of 7 | 0 of 7 | 0 of 7 | 1 of 7 |
| Anemia | Blood and lymphatic system disorders | 0 of 7 | 0 of 6 | 1 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Iron deficiency anemia | Blood and lymphatic system disorders | 1 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
| Atrial fibrillation | Cardiac disorders | 0 of 7 | 0 of 6 | 0 of 7 | 0 of 7 | 1 of 7 | 0 of 7 |
| Hearing impaired | Ear and labyrinth disorders | 0 of 7 | 0 of 6 | 1 of 7 | 0 of 7 | 0 of 7 | 0 of 7 |
Serious events with the highest arm-level rate: spinal laminectomy (16.7%), delirium (16.7%), gastral antral vascular ectasia (14.3%), nausea (14.3%), vomiting (14.3%).
The safety record reports serious adverse events and other adverse events by group, with an at-risk count for each category. For serious events, the affected counts were 2 of 7 in placebo every 2 weeks, 1 of 6 in the 0.1 g/kg every-2-weeks group, 0 of 7 in the 0.25 g/kg group, and 2 of 7 in the 0.4 g/kg group. For the every-4-weeks schedule, the counts were 2 of 7 in placebo, 0 of 7 in the 0.2 g/kg group, 1 of 8 in the 0.5 g/kg group, and 0 of 7 in the 0.8 g/kg group.
These are descriptive counts from groups with small at-risk numbers. They should be read as events reported during the study, not as precise estimates of comparative risk. The figures do not establish that a treatment caused or prevented an event, and the registry does not provide a statistical comparison of safety outcomes. Death counts are not reported in the registry record.
The registry lists serious-event terms including Spinal laminectomy, Delirium, and Gastric antral vascular ectasia, each at 16.7%, and Nausea, Vomiting, and Knee arthroplasty, each at 14.3%. The record does not make clear in these listed terms whether each percentage reflects a particular treatment arm or a broader event summary. These terms and percentages should not be interpreted as comparative treatment rates without that context.
13. What the Result Does, and Does Not, Mean
The posted results show the arm-specific means and standard deviations for a plasma Aβ1-40 area-under-the-curve endpoint after the final infusion period. Means vary across the placebo and Octagam 10% groups, and the observed spread within arms is considerable in several groups. These are descriptions of measurements among participants with available endpoint data, rather than estimates from a reported treatment-versus-placebo analysis.
The endpoint is a surrogate laboratory measure. It can describe a biological measurement over a specified time interval, but the registry record does not establish how changes in this measure relate to changes in cognition, daily function, or disease progression. The Mini Mental Status Examination was listed as a secondary outcome, but the primary results do not provide a clinical comparison for that measure.
The results do not establish that Octagam 10% improves or worsens Alzheimer’s disease, nor do they establish a dose-response relationship. They also do not show that one infusion schedule is superior to the other. The schedules differed in dose, duration, and endpoint measurement window, and no analysis separating those factors is reported. The absence of an estimable two-arm comparison further limits conclusions about treatment effects.
Small endpoint-group counts and substantial within-group variability mean that the arm means should be interpreted cautiously. No confidence intervals or inferential tests for the primary contrasts are reported in the registry record. Therefore, the posted data do not quantify the precision of a treatment effect or support a definitive claim about differences between the groups.
The appropriate statistical reading is narrow: the registry provides descriptive biological outcome summaries, along with safety counts, for this completed phase 2 trial. Those data can inform the description of what was observed in the analyzed participants, but they do not by themselves resolve clinical efficacy or comparative safety.
14. Why This Trial Matters Statistically
This study is statistically informative because it illustrates the gap between a randomized design and the inferential results available in a registry. Randomization can support interpretable treatment comparisons when outcomes are analyzed and reported with appropriate estimates and uncertainty. Here, the record gives arm-level primary endpoint means and standard deviations but says a two-arm comparison is not estimable. The distinction matters: a set of descriptive summaries is not equivalent to a tested treatment contrast.
The study also used multiple dose groups and two infusion schedules, with schedule-specific measurement windows for the primary endpoint. Such complexity can make interpretation dependent on a clearly specified analysis plan. The registry record does not report that plan, the sample-size justification, or how multiplicity was handled. Readers therefore cannot determine from the posted information which comparisons were prespecified or how the many outcome measures were intended to contribute to the trial’s conclusions.
The small endpoint counts and variability emphasize why uncertainty should accompany effect estimates. Means alone can appear separated even when the evidence is too imprecise to support a clear conclusion. Reporting confidence intervals and prespecified contrasts would help readers understand both the magnitude and precision of the findings; those details are not reported for the primary endpoint.
Finally, this trial focuses on efficacy-related surrogate parameters. Statistical interpretation must distinguish a change in a laboratory measure from a change in a clinical outcome. The registry’s primary endpoint can characterize plasma Aβ1-40 over time, but the posted results do not establish that this measure predicts a meaningful clinical effect. Keeping those questions separate is essential when assessing what a biomarker-focused study can and cannot show.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary endpoint summaries are based on small arm-specific counts, ranging from 5.0 to 8.0 participants, and several arms have large standard deviations. This combination limits the precision and stability of descriptive means. The registry does not provide confidence intervals for the primary endpoint, so the uncertainty around each mean and around any treatment contrast cannot be directly assessed from the posted results.
The record identifies the primary continuous comparison as missing or not estimable. It therefore does not supply a formal comparison with schedule-matched placebo groups. It also does not report a statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, or detailed handling of missing data. Those gaps prevent assessment of whether the posted summaries follow the trial’s planned inferential framework.
The analysis population required receipt of at least one infusion and at least one post-baseline efficacy assessment, and only participants with available data were included. The registry does not report the reasons for all missing endpoint data or provide sensitivity analyses for missingness. The enrollment count and endpoint-specific analysis counts consequently describe different sets of participants.
Interpretation across the infusion schedules is limited by differences in dose, treatment duration, and the periods used to calculate the area under the curve. The endpoint is a surrogate measure, and the registry record does not establish its relationship to clinical outcomes in this study. The safety summaries are also descriptive; their small at-risk counts and the lack of reported comparative analyses limit conclusions about differences in adverse-event risk.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Study of Octagam (Intravenous Immunoglobulin [IVIG]) 10% on the Treatment of Mild to Moderate Alzheimer's Disease — NCT00812565.
- Registry record last updated 2014-05-05; status last verified 2014-04.
- Results first posted 2014-05-05.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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19. Record Summary
NCT00812565 was a completed phase 2 randomized, quadruple-masked, parallel-group study sponsored by Octapharma. It enrolled 58 participants with Alzheimer’s disease and compared placebo with three Octagam 10% doses under each of two infusion schedules. The primary outcome was change in plasma Aβ1-40 area under the curve after the last infusion, measured relative to a pre-infusion trough level.
The registry reports arm-level means, standard deviations, and endpoint counts, but no estimable two-arm comparison for the primary continuous outcome. The analysis included participants with available data who met the stated full analysis set definition. Serious and other adverse-event counts are also reported by group. The record does not report the study’s sample-size justification, detailed statistical analysis plan, multiplicity approach, or comprehensive missing-data methods. The posted primary summaries are descriptive and do not establish a clinical treatment effect.