Trial Outcomes & Findings for IVIG (Gamunex-C) Treatment Study for POTS Subjects (NCT NCT03919773)
NCT ID: NCT03919773
Last Updated: 2024-09-19
Results Overview
Primary outcome was change in autonomic symptom burden, assessed by total COMPASS-31 (sum of scaled subscores), comparing assessment at week 13 (2 weeks after final infusion) minus the assessment at baseline. This questionnaire generates a weighted score from 0 to 100, and questions fall into one of six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor function. A COMPASS-31 (Composite Autonomic Symptom Score-31) score of ≥20 suggests moderate-to-severe autonomic dysfunction. Higher scores indicate more severe symptoms. A reduction in score (negative change over time) indicates better outcome or response to treatment.
COMPLETED
PHASE1/PHASE2
30 participants
Baseline,13 weeks
2024-09-19
Participant Flow
Participant milestones
| Measure |
IVIG First, Then Albumin
Once qualified for the study and starting treatment, there are two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each. All the study visits and treatment visits are outpatient visits.
Treatment period 1: IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total, 8 infusions).
Washout period: 6 weeks
Treatment period 2: Albumin infusion: (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total, 8 infusions). This will be the matching control treatment used in the study.
|
Albumin First, Then IVIG
Once qualified for the study and starting treatment, there are two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each. All the study visits and treatment visits are outpatient visits.
Treatment period 1: Albumin infusion: (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total, 8 infusions). This will be the matching control treatment used in the study.
Washout period: 6 weeks
Treatment period 2: IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total, 8 infusions).
|
|---|---|---|
|
First Intervention- (12 Weeks)
STARTED
|
16
|
14
|
|
First Intervention- (12 Weeks)
COMPLETED
|
15
|
12
|
|
First Intervention- (12 Weeks)
NOT COMPLETED
|
1
|
2
|
|
Washout (6 Weeks)
STARTED
|
15
|
12
|
|
Washout (6 Weeks)
COMPLETED
|
12
|
12
|
|
Washout (6 Weeks)
NOT COMPLETED
|
3
|
0
|
|
Second Intervention-(12 Weeks)
STARTED
|
12
|
12
|
|
Second Intervention-(12 Weeks)
COMPLETED
|
10
|
11
|
|
Second Intervention-(12 Weeks)
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
IVIG First, Then Albumin
Once qualified for the study and starting treatment, there are two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each. All the study visits and treatment visits are outpatient visits.
Treatment period 1: IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total, 8 infusions).
Washout period: 6 weeks
Treatment period 2: Albumin infusion: (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total, 8 infusions). This will be the matching control treatment used in the study.
|
Albumin First, Then IVIG
Once qualified for the study and starting treatment, there are two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each. All the study visits and treatment visits are outpatient visits.
Treatment period 1: Albumin infusion: (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total, 8 infusions). This will be the matching control treatment used in the study.
Washout period: 6 weeks
Treatment period 2: IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total, 8 infusions).
|
|---|---|---|
|
First Intervention- (12 Weeks)
Adverse Event
|
1
|
1
|
|
First Intervention- (12 Weeks)
Protocol Violation
|
0
|
1
|
Baseline Characteristics
IVIG (Gamunex-C) Treatment Study for POTS Subjects
Baseline characteristics by cohort
| Measure |
IVIG First, Then Albumin
n=16 Participants
Once qualified for the study and starting treatment, there are two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each. All the study visits and treatment visits are outpatient visits.
Treatment period 1: IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total, 8 infusions).
Washout period: 6 weeks
Treatment period 2: Albumin infusion: (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total, 8 infusions). This will be the matching control treatment used in the study.
|
Albumin First, Then IVIG
n=14 Participants
Once qualified for the study and starting treatment, there are two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each. All the study visits and treatment visits are outpatient visits.
Treatment period 1: Albumin infusion: (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total, 8 infusions). This will be the matching control treatment used in the study.
Washout period: 6 weeks
Treatment period 2: IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total, 8 infusions).
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.7 years
STANDARD_DEVIATION 8.75 • n=5 Participants
|
31.9 years
STANDARD_DEVIATION 9.99 • n=7 Participants
|
31.8 years
STANDARD_DEVIATION 9.19 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
14 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Time since symptom onset (years), median (IQR)
|
4.0 years
n=5 Participants
|
4.0 years
n=7 Participants
|
4.0 years
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline,13 weeksPopulation: The primary outcome measure was assessed only during the first treatment phase and hence, only 15 participants who received IVIG treatment and 13 participants who received Albumin treatment were analyzed for this primary outcome measure. The 1 patient (Albumin- First intervention group) who was a protocol violation was included in the analysis. The 2 patients (1 each from IVIG and Albumin- first intervention groups) with SAEs were not included in the analysis since lost to follow-up.
Primary outcome was change in autonomic symptom burden, assessed by total COMPASS-31 (sum of scaled subscores), comparing assessment at week 13 (2 weeks after final infusion) minus the assessment at baseline. This questionnaire generates a weighted score from 0 to 100, and questions fall into one of six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor function. A COMPASS-31 (Composite Autonomic Symptom Score-31) score of ≥20 suggests moderate-to-severe autonomic dysfunction. Higher scores indicate more severe symptoms. A reduction in score (negative change over time) indicates better outcome or response to treatment.
Outcome measures
| Measure |
Treatment IVIG Arm
n=15 Participants
IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total).
IVIG: If you participate in this study there will be 18 scheduled treatment infusions during the 30 week study period. All the study visits and treatment visits will be outpatient visits.
Once you qualify to participate in the study and begin treatment, there will be two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each.
|
Treatment Albumin Arm
n=13 Participants
albumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during
Albumin: This will be the matching placebo used in the study.
|
|---|---|---|
|
Change in Symptoms Measured by Change in COMPASS-31 Score (After Initial Treatment Phase)
|
-5.5 score on a scale
Interval -27.0 to 21.0
|
-10.6 score on a scale
Interval -28.0 to 2.0
|
SECONDARY outcome
Timeframe: 13 weeksPopulation: The secondary outcome measure was assessed only for the first treatment phase and hence, only 15 participants who received IVIG treatment and 13 participants who received Albumin treatment were analyzed for this outcome measure. The 1 patient (Albumin- First intervention group) who was a protocol violation was included in this analysis . The 2 patients (1 each from IVIG and Albumin- first intervention groups) with SAEs were not included in the analysis since lost to follow-up.
The count of participants with clinical improvement at 13 weeks is being reported here. Clinical improvement was defined as a reduction of the COMPASS-31 total score by 20% or more. Lower scores are associated with improvement and a 20% reduction was used as a meaningful change in previous studies of POTS
Outcome measures
| Measure |
Treatment IVIG Arm
n=15 Participants
IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total).
IVIG: If you participate in this study there will be 18 scheduled treatment infusions during the 30 week study period. All the study visits and treatment visits will be outpatient visits.
Once you qualify to participate in the study and begin treatment, there will be two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each.
|
Treatment Albumin Arm
n=13 Participants
albumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during
Albumin: This will be the matching placebo used in the study.
|
|---|---|---|
|
Number of Participants With Clinical Improvement
|
7 participants
|
5 participants
|
Adverse Events
Treatment IVIG Arm
Treatment Albumin Arm
Serious adverse events
| Measure |
Treatment IVIG Arm
n=28 participants at risk
IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total).
IVIG: If you participate in this study there will be 18 scheduled treatment infusions during the 30 week study period. All the study visits and treatment visits will be outpatient visits.
Once you qualify to participate in the study and begin treatment, there will be two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each.
|
Treatment Albumin Arm
n=26 participants at risk
albumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during
Albumin: This will be the matching placebo used in the study.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/28 • 30 weeks
|
3.8%
1/26 • Number of events 1 • 30 weeks
|
|
Nervous system disorders
Magnetic resonance imaging of head abnormal (finding)
|
3.6%
1/28 • Number of events 1 • 30 weeks
|
0.00%
0/26 • 30 weeks
|
|
Nervous system disorders
Severe Headache
|
3.6%
1/28 • Number of events 1 • 30 weeks
|
0.00%
0/26 • 30 weeks
|
|
Reproductive system and breast disorders
Ovarian Cyst rupture
|
0.00%
0/28 • 30 weeks
|
3.8%
1/26 • Number of events 1 • 30 weeks
|
Other adverse events
| Measure |
Treatment IVIG Arm
n=28 participants at risk
IVIG (Gammunex-C) infusion (0.4 gm/kg) every week for 4 weeks, then every 2 weeks for 8 weeks (12 weeks total).
IVIG: If you participate in this study there will be 18 scheduled treatment infusions during the 30 week study period. All the study visits and treatment visits will be outpatient visits.
Once you qualify to participate in the study and begin treatment, there will be two 12 week treatment periods separated by a 6 week washout period. The infusion visits will take approximately 3-4 hours each.
|
Treatment Albumin Arm
n=26 participants at risk
albumin infusion (0.4 gm/kg) every week for 4 weeks then every 2 weeks for 8 weeks (12 weeks total) during
Albumin: This will be the matching placebo used in the study.
|
|---|---|---|
|
Nervous system disorders
Headache
|
64.3%
18/28 • Number of events 18 • 30 weeks
|
53.8%
14/26 • Number of events 14 • 30 weeks
|
|
General disorders
Fatigue
|
28.6%
8/28 • Number of events 8 • 30 weeks
|
34.6%
9/26 • Number of events 9 • 30 weeks
|
|
General disorders
Pain
|
28.6%
8/28 • Number of events 8 • 30 weeks
|
30.8%
8/26 • Number of events 8 • 30 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
28.6%
8/28 • Number of events 8 • 30 weeks
|
7.7%
2/26 • Number of events 2 • 30 weeks
|
|
Gastrointestinal disorders
gastrointestinal symptom
|
21.4%
6/28 • Number of events 6 • 30 weeks
|
19.2%
5/26 • Number of events 5 • 30 weeks
|
|
General disorders
Fever
|
7.1%
2/28 • Number of events 2 • 30 weeks
|
7.7%
2/26 • Number of events 2 • 30 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place