Effect of Raxibacumab on Immunogenicity of Anthrax Vaccine Adsorbed
Study Details
Study Description
Brief Summary
This study, as a post-marketing commitment to the Food and Drug Administration, is designed to detect the effect of raxibacumab on anthrax vaccine adsorbed (AVA) immunogenicity in a healthy volunteer population. This is a randomized, open-label, parallel group, two arm study to compare the immunogenicity of AVA at 4 weeks after the first AVA dose, when AVA is administered alone or concomitantly with raxibacumab. The study is planned to enroll approximately 30 to 534 subjects in up to 3 cohorts. The total duration of the study will be approximately 26 weeks. The dates reflect cohort 1.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Anthrax Vaccine Adsorbed Subjects will be administered subcutaneous (SC) 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks). |
Biological: AVA
Sterile, milky-white suspension with dosage level of 0.5 mL for SC administration
|
| Experimental: AVA + Raxibacumab Subjects will be administered SC 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks), with the first AVA dose administered immediately after completion of a single intravenous (IV) infusion 40 milligram (mg)/kilogram (kg) raxibacumab dose. Subjects will be premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
Biological: AVA
Sterile, milky-white suspension with dosage level of 0.5 mL for SC administration
Biological: Raxibacumab
Sterile, liquid formulation with unit dose strength of 40 mg/ kg for IV administration
Drug: Diphenhydramine
Depending upon the labelling of the specific product chosen, 25 - 50 mg will be administered orally or IV
|
Outcome Measures
Primary Outcome Measures
- Ratio of Geometric Mean Concentrations (GMC) of Anti-protective Antigen (PA) Antibody (Ab) at 4 Weeks (Day 29) After the First AVA Dose (Prior to the Third AVA Dose), Between the AVA Alone and the AVA With Raxibacumab Treatment Groups [Day 29]
Ratio of the GMC of anti-PA Ab between AVA alone and the AVA with raxibacumab treatment group was assessed to compare the immunogenicity of AVA at 4 weeks after the first AVA dose (prior to the third AVA dose). Serum AVA derived anti-PA Ab concentrations were determined using an approved immunoassay. Per Protocol (PP) population was used in analysis which comprised of all analyzable participants (those who received at least the Week 0 [Day 1] and Week 2 [Day 15] AVA doses within the protocol specified visit window; receive the raxibacumab dose, if randomized to Treatment Group 2 and; completed the primary study endpoint assessment [anti-PA Ab concentration at Week 4]).
Secondary Outcome Measures
- Ratio of GMC of Anti-PA Ab at Weeks 8 and 26 (Days 57 and 183) After the First AVA Dose, Between the AVA Alone and AVA With Raxibacumab Treatment Groups [Days 57 and 183]
Anti-PA antibody concentrations were collected at Weeks 8 and 26 after the first AVA dose. Serum AVA derived anti-PA Ab concentrations were determined using an approved immunoassay. The GMCs with corresponding 95% CI were calculated for each treatment group at each timepoint. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
- Percentage of Participants Who Seroconvert, at Weeks 4, 8, and 26 (Days 29, 57 and 183) After the First AVA Dose, Between the AVA Alone and the AVA With Raxibacumab Treatment Groups [Days 29, 57 and 183]
The percentage of participants, with corresponding 95% CI based on Wilson's method, who seroconvert (seroconversion is defined as a >4-fold increase in toxin neutralizing activity [TNA] titer) was summarized, at Weeks 4, 8 and 26 after the first AVA dose for both arms separately. Serum TNA titer was determined using a cell-based assay.
- Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE) [Up to Day 183]
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE resulting in death, is life threatening (ie, an immediate threat to life), inpatient hospitalization, prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or any other situation which is medically important and may jeopardize the participant or may require medical or surgical intervention or events associated with liver injury and impaired liver function is categorized as SAE. The Safety population was comprised of all randomized participants who received at least one dose of AVA.
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points [Baseline and up to Day 183]
SBP and DBP were measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
- Change From Baseline in Heart Rate at Indicated Time Points [Baseline and up to Day 183]
Heart rate was measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
- Change From Baseline in Respiratory Rate at Indicated Time Points [Baseline and up to Day 183]
Respiratory rate was measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
- Change From Baseline in Temperature at Indicated Time Points [Baseline and up to Day 183]
Temperature was measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
- Number of Participants With Hematology Parameters Outside Normal Range [Up to Day 57]
Hematology parameters included assessment of platelet count, erythrocytes, leukocytes , reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin and hematocrit. Here high is equal to above the upper limit of the normal range, low is equal to below the lower limit of the normal range. Participants are counted in the category that their value changes to (low, normal or high), unless there is no change in their category. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
- Number of Participants With Clinical Chemistry Parameters Outside Normal Range [Up to Day 57]
Blood samples were collected to evaluate clinical chemistry parameters, which included assessment of urea nitrogen (UN), creatinine, chloride, glucose, magnesium, total protein, potassium, chloride, total Carbon dioxide (CO2), sodium, calcium (cal), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total and direct bilirubin ( D.bili), albumin and calculated creatinine clearance. Here high is equal to above the upper limit of the normal range, low is equal to below the lower limit of the normal range. Participants are counted in the category that their value changes to (low, normal or high), unless there is no change in their category. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
- Number of Participants With Urinalysis Parameters [Day 57]
Urinalysis parameters included amorphous crystals, bacteria, bilirubin, calcium oxalate (Ca Ox) crystals, choriogonadotropin beta, clarity, color, crystals of Ca Ox, erythrocytes, glucose, hemoglobin, ketone bodies, ketones, leukocyte cell clumps, leukocyte esterase, leukocytes, mucous threads, nitrite, occult blood, protein, specific gravity, squamous epithelial cells, turbidity, urobilinogen, and transitional epithelial cells. In urinalysis test plus sign (+) indicates increase in the level of the parameters.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination and laboratory tests
-
Men and women between 18 to 65 years of age
-
Willing and able to adhere to the procedures stated in the protocol.
-
Female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
Non-reproductive potential defined as:
Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
Reproductive potential and agrees to follow one of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP), from 30 days prior to the first dose of study medication and until after the last dose of study medication and completion of the follow-up visit at Day 183 (at least five terminal half-lives for raxibacumab).
Exclusion Criteria:
-
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or non-investigational study vaccine/product (pharmaceutical product or device).
-
Be a member of the military, a laboratory worker, first responder, health care worker, or otherwise be at higher risk of exposure to anthrax.
-
History of regular alcohol consumption within 1 month of the study defined as:
An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
-
Female planning to become pregnant or planning to discontinue contraceptive precautions before the Day 183 study visit.
-
Pregnant (confirmed by a serum or urine hCG test) or lactating female.
-
Alanine aminotransferase (ALT) and bilirubin >1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
-
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
-
Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).
-
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test results at screening or within 3 months prior to first dose of study treatment.
-
A positive pre-study drug/alcohol screen.
-
A positive test for HIV antibody.
-
History of sensitivity to any of the study medications, or components thereof (especially latex and aluminium) or a history of other known drug allergies that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation.
-
Have previously been vaccinated against PA.
-
Have an anti-PA Ab concentration >2 times the lower limit of quantitation at screening.
-
Administration of immunoglobulins not included in this trial and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
-
Administration of long-acting immune-modifying drugs (e.g. infliximab) within six months prior to the first vaccine dose or expected administration at any time during the study period.
-
Chronic administration (defined as more than 14 consecutive days) of systemic immunosupressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled, topical and intra-articular corticosteroids are allowed.
-
Administration or planned administration of a vaccine not foreseen by the study protocol within the period starting 35 days before the first dose of study vaccine(s) and ending 30 days after the last dose of study vaccine. This includes any type of vaccine such as (but not limited to) live, inactivated, and subunit vaccines. Influenza vaccines are permitted after Week 8.
-
Subjects must abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study.
-
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
-
Any condition which, in the opinion of the investigator, prevents the subject from participating in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Edgewater | Florida | United States | 32132 |
| 2 | GSK Investigational Site | Overland Park | Kansas | United States | 66211 |
| 3 | GSK Investigational Site | Knoxville | Tennessee | United States | 37920 |
Sponsors and Collaborators
- Emergent BioSolutions
- GlaxoSmithKline
Investigators
- Study Director: Paul-Andre deLame, MD, Emergent BioSolutions Inc
Study Documents (Full-Text)
More Information
Publications
None provided.- 201436
Study Results
Participant Flow
| Recruitment Details | This study included healthy volunteers who were not previously immunized against protective antigen. 573 participants were randomized with 566 receiving study treatment and 537 completed the study. |
|---|---|
| Pre-assignment Detail | A total of 573 participants were randomized with 566 receiving study treatment and 537 completed the study. |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered Anthrax vaccine adsorbed (AVA) subcutaneous (SC) 0.5 milliliter (mL) on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29. with the first AVA dose administered immediately after completion of a single 40 milligram/kilogram (mg/kg) intravenous (IV) infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Period Title: Overall Study | ||
| STARTED | 287 | 286 |
| Received Study Treatment | 286 | 280 |
| COMPLETED | 272 | 265 |
| NOT COMPLETED | 15 | 21 |
Baseline Characteristics
| Arm/Group Title | AVA Alone | AVA+Raxibacumab | Total |
|---|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. | Total of all reporting groups |
| Overall Participants | 287 | 286 | 573 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
36.2
(12.78)
|
36.1
(12.06)
|
36.2
(12.42)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
150
52.3%
|
142
49.7%
|
292
51%
|
| Male |
137
47.7%
|
144
50.3%
|
281
49%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
216
75.3%
|
221
77.3%
|
437
76.3%
|
| Black or African American |
61
21.3%
|
56
19.6%
|
117
20.4%
|
| American Indian or Alaska Native |
7
2.4%
|
1
0.3%
|
8
1.4%
|
| Asian |
2
0.7%
|
5
1.7%
|
7
1.2%
|
| Multiple |
1
0.3%
|
2
0.7%
|
3
0.5%
|
| Unknown |
0
0%
|
1
0.3%
|
1
0.2%
|
Outcome Measures
| Title | Ratio of Geometric Mean Concentrations (GMC) of Anti-protective Antigen (PA) Antibody (Ab) at 4 Weeks (Day 29) After the First AVA Dose (Prior to the Third AVA Dose), Between the AVA Alone and the AVA With Raxibacumab Treatment Groups |
|---|---|
| Description | Ratio of the GMC of anti-PA Ab between AVA alone and the AVA with raxibacumab treatment group was assessed to compare the immunogenicity of AVA at 4 weeks after the first AVA dose (prior to the third AVA dose). Serum AVA derived anti-PA Ab concentrations were determined using an approved immunoassay. Per Protocol (PP) population was used in analysis which comprised of all analyzable participants (those who received at least the Week 0 [Day 1] and Week 2 [Day 15] AVA doses within the protocol specified visit window; receive the raxibacumab dose, if randomized to Treatment Group 2 and; completed the primary study endpoint assessment [anti-PA Ab concentration at Week 4]). |
| Time Frame | Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP Population. |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 276 | 269 |
| Geometric Mean (95% Confidence Interval) [Microgram/milliliter (µg/mL)] |
26.516
|
22.477
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | AVA Alone, AVA+Raxibacumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | If the upper bound of the 90% confidence interval (CI) or the ratio of anti-PA Ab (attributable to AVA) GMCs between the AVA and the AVA + raxibacumab groups at Week 4 is less than 1.5, non-inferiority was to be established. | |
| Statistical Test of Hypothesis | p-Value | 0.0016 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio |
| Estimated Value | 1.18 | |
| Confidence Interval |
(2-Sided) 90% 1.03 to 1.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Ratio of GMC of Anti-PA Ab at Weeks 8 and 26 (Days 57 and 183) After the First AVA Dose, Between the AVA Alone and AVA With Raxibacumab Treatment Groups |
|---|---|
| Description | Anti-PA antibody concentrations were collected at Weeks 8 and 26 after the first AVA dose. Serum AVA derived anti-PA Ab concentrations were determined using an approved immunoassay. The GMCs with corresponding 95% CI were calculated for each treatment group at each timepoint. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. |
| Time Frame | Days 57 and 183 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP Population. |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 275 | 267 |
| Week 8, n=275, 267 |
50.470
|
46.095
|
| Week 26, n=267, 258 |
10.007
|
10.231
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | AVA Alone, AVA+Raxibacumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio |
| Estimated Value | 1.09 | |
| Confidence Interval |
(2-Sided) 90% 0.98 to 1.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Week 8 | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | AVA Alone, AVA+Raxibacumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio |
| Estimated Value | 0.98 | |
| Confidence Interval |
(2-Sided) 90% 0.89 to 1.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Week 26 | |
| Title | Percentage of Participants Who Seroconvert, at Weeks 4, 8, and 26 (Days 29, 57 and 183) After the First AVA Dose, Between the AVA Alone and the AVA With Raxibacumab Treatment Groups |
|---|---|
| Description | The percentage of participants, with corresponding 95% CI based on Wilson's method, who seroconvert (seroconversion is defined as a >4-fold increase in toxin neutralizing activity [TNA] titer) was summarized, at Weeks 4, 8 and 26 after the first AVA dose for both arms separately. Serum TNA titer was determined using a cell-based assay. |
| Time Frame | Days 29, 57 and 183 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP Population. |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 276 | 269 |
| Week 4 |
76.4
26.6%
|
99.3
34.7%
|
| Week 8 |
95.3
33.2%
|
98.1
34.3%
|
| Week 26 |
31.9
11.1%
|
32.0
11.2%
|
| Title | Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE) |
|---|---|
| Description | An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE resulting in death, is life threatening (ie, an immediate threat to life), inpatient hospitalization, prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or any other situation which is medically important and may jeopardize the participant or may require medical or surgical intervention or events associated with liver injury and impaired liver function is categorized as SAE. The Safety population was comprised of all randomized participants who received at least one dose of AVA. |
| Time Frame | Up to Day 183 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| Non-serious AEs |
85
29.6%
|
80
28%
|
| SAE |
5
1.7%
|
3
1%
|
| Title | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points |
|---|---|
| Description | SBP and DBP were measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. |
| Time Frame | Baseline and up to Day 183 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29. with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| SBP, Day 1, n=286, 280 |
-3.4
(9.2)
|
-3.8
(9.6)
|
| SBP, Day 29, n=283, 279 |
0.6
(9.9)
|
1.9
(9.9)
|
| SBP, Day 57, n=282, 275 |
1.8
(10.9)
|
2.2
(10.3)
|
| SBP, Day 183, n=273, 266 |
2.4
(10.6)
|
1.5
(9.9)
|
| DBP, Day 1, n=286, 280 |
-2.7
(6.9)
|
-3.1
(6.8)
|
| DBP, Day 29, n=283, 279 |
1.0
(7.3)
|
1.6
(6.5)
|
| DBP, Day 57, n=282, 275 |
1.9
(7.4)
|
2.3
(7.4)
|
| DBP, Day 183, n=273, 266 |
2.3
(8.4)
|
2.5
(7.9)
|
| Title | Change From Baseline in Heart Rate at Indicated Time Points |
|---|---|
| Description | Heart rate was measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. |
| Time Frame | Baseline and up to Day 183 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| Day 1, n=286, 280 |
-0.3
(10.4)
|
-0.8
(10.5)
|
| Day 29, n=283, 279 |
-0.4
(10.5)
|
-0.4
(10.5)
|
| Day 57, n=282, 275 |
-1.2
(10.6)
|
-0.9
(11.2)
|
| Day 183, n=273, 266 |
0.9
(11.7)
|
0.7
(11.5)
|
| Title | Change From Baseline in Respiratory Rate at Indicated Time Points |
|---|---|
| Description | Respiratory rate was measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. |
| Time Frame | Baseline and up to Day 183 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| Day 1, n=286, 280 |
-0.4
(1.5)
|
-0.3
(1.5)
|
| Day 29, n=283, 279 |
-0.1
(1.4)
|
-0.1
(1.4)
|
| Day 57, n=282, 276 |
-0.1
(1.5)
|
-0.1
(1.3)
|
| Day 183, n=273, 266 |
-0.3
(1.6)
|
-0.2
(1.5)
|
| Title | Change From Baseline in Temperature at Indicated Time Points |
|---|---|
| Description | Temperature was measured in semi-supine position after 5 minutes rest. Values at Day -1 were considered as Baseline values. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. |
| Time Frame | Baseline and up to Day 183 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| Day 1, n=286, 280 |
-0.04
(0.26)
|
0.02
(0.27)
|
| Day 29, n=283, 279 |
-0.04
(0.24)
|
-0.03
(0.31)
|
| Day 57, n=282, 276 |
-0.05
(0.25)
|
-0.02
(0.25)
|
| Day 183, n=272, 266 |
-0.04
(0.277)
|
-0.01
(0.26)
|
| Title | Number of Participants With Hematology Parameters Outside Normal Range |
|---|---|
| Description | Hematology parameters included assessment of platelet count, erythrocytes, leukocytes , reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin and hematocrit. Here high is equal to above the upper limit of the normal range, low is equal to below the lower limit of the normal range. Participants are counted in the category that their value changes to (low, normal or high), unless there is no change in their category. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. |
| Time Frame | Up to Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| Eosinophils 10^9/Liter (L) Low, Week 4, n=282, 278 |
0
0%
|
0
0%
|
| Eosinophils 10^9/L High, Week 4, n=282, 278 |
4
1.4%
|
6
2.1%
|
| Eosinophils 10^9/L, Low, Week 8, n=281, 276 |
0
0%
|
0
0%
|
| Eosinophils 10^9/L, High, Week 8, n=281, 276 |
7
2.4%
|
5
1.7%
|
| Basophils 10^9/L, Low, Week 4, n=282, 278 |
0
0%
|
0
0%
|
| Basophils 10^9/L, High, Week 4, n=282, 278 |
0
0%
|
0
0%
|
| Basophils 10^9/L, Low, Week 8, n=281, 276 |
0
0%
|
0
0%
|
| Basophils 10^9/L, High, Week 8, n=281, 276 |
0
0%
|
0
0%
|
| Hematocrit percent (%) Low, Week 4, n=283, 279 |
7
2.4%
|
6
2.1%
|
| Hematocrit %, High, Week 4, n=283, 279 |
2
0.7%
|
1
0.3%
|
| Hematocrit %, Low, Week 8, n=281, 276 |
6
2.1%
|
9
3.1%
|
| Hematocrit %, High, Week 8, n=281, 276 |
2
0.7%
|
2
0.7%
|
| Hemoglobin gram/Liter (g/L) Low,Week 4,n=283, 279 |
7
2.4%
|
3
1%
|
| Hemoglobin g/L, High, Week 4, n=283, 279 |
4
1.4%
|
1
0.3%
|
| Hemoglobin g/L, Low, Week 8, n=281, 276 |
7
2.4%
|
10
3.5%
|
| Hemoglobin g/L, High, Week 8, n=281, 276 |
3
1%
|
2
0.7%
|
| Lymphocytes 10^9/L , Low, Week 4, n=282, 278 |
3
1%
|
1
0.3%
|
| Lymphocytes 10^9/L , High, Week 4, n=282, 278 |
0
0%
|
1
0.3%
|
| Lymphocytes 10^9/L, Low, Week 8, n=281, 276 |
2
0.7%
|
4
1.4%
|
| Lymphocytes 10^9/L, High, Week 8, n=281, 276 |
0
0%
|
0
0%
|
| MCH picogram (pg), Low, Week 4, n=283, 279 |
2
0.7%
|
1
0.3%
|
| MCH pg, High, Week 4, n=283, 279 |
0
0%
|
0
0%
|
| MCH pg, Low, Week 8, n=281, 276 |
2
0.7%
|
5
1.7%
|
| MCH pg, High, Week 8, n=281, 276 |
0
0%
|
0
0%
|
| MCHC g/L, Low, Week 4, n=283, 279 |
3
1%
|
3
1%
|
| MCHC g/L, High, Week 4, n=283, 279 |
19
6.6%
|
17
5.9%
|
| MCHC g/L, Low, Week 8, n=281, 276 |
3
1%
|
7
2.4%
|
| MCHC g/L, High, Week 8, n=281, 276 |
16
5.6%
|
12
4.2%
|
| MCV femtoliters (fL), Low, Week 4, n=283, 279 |
2
0.7%
|
2
0.7%
|
| MCV fL, High, Week 4, n=283, 279 |
0
0%
|
1
0.3%
|
| MCV fL, Low, Week 8, n=281, 276 |
3
1%
|
2
0.7%
|
| MCV fL, High, Week 8, n=281, 276 |
0
0%
|
0
0%
|
| Monocytes 10^9/L , Low, Week 4, n=282, 278 |
0
0%
|
0
0%
|
| Monocytes 10^9/L, High, Week 4, n=282, 278 |
3
1%
|
2
0.7%
|
| Monocytes 10^9/L, Low, Week 8, n=281, 276 |
0
0%
|
0
0%
|
| Monocytes 10^9/L, High, Week 8, n=281, 276 |
0
0%
|
1
0.3%
|
| Neutrophils 10^9/L, Low, Week 4, n=283, 279 |
7
2.4%
|
8
2.8%
|
| Neutrophils 10^9/L, High, Week 4, n=283, 279 |
3
1%
|
2
0.7%
|
| Neutrophils 10^9/L, Low, Week 8, n=281, 276 |
5
1.7%
|
6
2.1%
|
| Neutrophils 10^9/L, High, Week 8, n=281, 276 |
1
0.3%
|
6
2.1%
|
| Erythrocytes 10^12/L, Low, Week 4, n=283, 279 |
6
2.1%
|
4
1.4%
|
| Erythrocytes 10^12/L, High, Week 4, n=283, 279 |
4
1.4%
|
7
2.4%
|
| Erythrocytes 10^12/L, Low, Week 8, n=281, 276 |
2
0.7%
|
8
2.8%
|
| Erythrocytes 10^12/L, High, Week 8, n=281, 276 |
6
2.1%
|
3
1%
|
| Leukocytes 10^9/L, Low, Week 4, n=283, 279 |
15
5.2%
|
12
4.2%
|
| Leukocytes 10^9/L, High, Week 4, n=283, 279 |
2
0.7%
|
2
0.7%
|
| Leukocytes 10^9/L, Low, Week 8, n=281, 276 |
6
2.1%
|
10
3.5%
|
| Leukocytes 10^9/L, High, Week 8, n=281, 276 |
1
0.3%
|
5
1.7%
|
| Reticulocytes 10^12/L, Low, Week 4, n=283, 279 |
1
0.3%
|
0
0%
|
| Reticulocytes 10^12/L, High, Week 4, n=283, 279 |
1
0.3%
|
3
1%
|
| Reticulocytes 10^12/L, Low, Week 8, n=281, 276 |
1
0.3%
|
1
0.3%
|
| Reticulocytes 10^12/L, High, Week 8, n=281, 276 |
5
1.7%
|
3
1%
|
| Platelet 10^9/L, Low, Week 4, n=282, 279 |
6
2.1%
|
4
1.4%
|
| Platelet 10^9/L, High, Week 4, n=282, 279 |
0
0%
|
0
0%
|
| Platelet 10^9/L, Low, Week 8, n=280, 276 |
4
1.4%
|
4
1.4%
|
| Platelet 10^9/L, High, Week 8, n=280, 276 |
1
0.3%
|
0
0%
|
| Title | Number of Participants With Clinical Chemistry Parameters Outside Normal Range |
|---|---|
| Description | Blood samples were collected to evaluate clinical chemistry parameters, which included assessment of urea nitrogen (UN), creatinine, chloride, glucose, magnesium, total protein, potassium, chloride, total Carbon dioxide (CO2), sodium, calcium (cal), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total and direct bilirubin ( D.bili), albumin and calculated creatinine clearance. Here high is equal to above the upper limit of the normal range, low is equal to below the lower limit of the normal range. Participants are counted in the category that their value changes to (low, normal or high), unless there is no change in their category. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed. |
| Time Frame | Up to Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population. |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| Albumin g/L, Low, Week 4, n=283, 279 |
6
2.1%
|
2
0.7%
|
| Albumin g/L, High, Week 4, n=283, 279 |
1
0.3%
|
0
0%
|
| Albumin g/L, Low, Week 8, n=282, 275 |
2
0.7%
|
1
0.3%
|
| Albumin g/L, High, Week 8, n=282, 275 |
0
0%
|
0
0%
|
| ALP units/liter (U/L), Low, Week 4, n=283, 279 |
3
1%
|
5
1.7%
|
| ALP U/L, High, Week 4, n=283, 279 |
14
4.9%
|
20
7%
|
| ALP U/L, Low, Week 8, n=282, 275 |
2
0.7%
|
2
0.7%
|
| ALP U/L, High, Week 8, n=282, 275 |
13
4.5%
|
19
6.6%
|
| ALT U/L, Low, Week 4, n=283, 279 |
45
15.7%
|
44
15.4%
|
| ALT U/L, High, Week 4, n=283, 279 |
7
2.4%
|
4
1.4%
|
| ALT U/L, Low, Week 8, n=282, 275 |
39
13.6%
|
42
14.7%
|
| ALT U/L, High, Week 8, n=282, 275 |
7
2.4%
|
6
2.1%
|
| AST U/L, Low, Week 4, n=283, 279 |
41
14.3%
|
37
12.9%
|
| AST U/L, High, Week 4, n=283, 279 |
7
2.4%
|
5
1.7%
|
| AST U/L, Low, Week 8, n=282, 275 |
38
13.2%
|
34
11.9%
|
| AST U/L, High, Week 8, n=282, 275 |
6
2.1%
|
10
3.5%
|
| D.bili micromole/Liter (µmol/L) LowWeek4,n=274,263 |
0
0%
|
0
0%
|
| D.bili µmol/L, High, Week 4, n=274, 263 |
5
1.7%
|
3
1%
|
| D.bili µmol/L, Low, Week 8, n=274, 261 |
0
0%
|
0
0%
|
| D.bili µmol/L, High, Week 8, n=274, 261 |
5
1.7%
|
9
3.1%
|
| Bili µmol/L, Low, Week 4, n=280, 279 |
5
1.7%
|
4
1.4%
|
| Bili µmol/L, High, Week 4, n=280, 279 |
1
0.3%
|
5
1.7%
|
| Bili µmol/L, Low, Week 8, n=280, 273 |
3
1%
|
2
0.7%
|
| Bili µmol/L, High, Week 8, n=280, 273 |
2
0.7%
|
7
2.4%
|
| Cal,millimole/Liter (mmol/L)Low,Week 4,n=283, 279 |
6
2.1%
|
4
1.4%
|
| Cal mmol/L, High, Week 4, n=283, 279 |
2
0.7%
|
4
1.4%
|
| Cal mmol/L, Low, Week 8, n=282, 275 |
12
4.2%
|
10
3.5%
|
| Cal mmol/L, High, Week 8, n=282, 275 |
0
0%
|
3
1%
|
| Chloride mmol/L, Low, Week 4, n=283, 279 |
0
0%
|
0
0%
|
| Chloride mmol/L, High, Week 4, n=283, 279 |
19
6.6%
|
12
4.2%
|
| Chloride mmol/L, Low, Week 8, n=282, 275 |
0
0%
|
0
0%
|
| Chloride mmol/L, High, Week 8, n=282, 275 |
12
4.2%
|
9
3.1%
|
| CO2 mmol/L, Low, Week 4, n=283, 279 |
7
2.4%
|
11
3.8%
|
| CO2 mmol/L, High, Week 4, n=283, 279 |
14
4.9%
|
12
4.2%
|
| CO2 mmol/L, Low, Week 8, n=282, 275 |
6
2.1%
|
14
4.9%
|
| CO2 mmol/L, High, Week 8, n=282, 275 |
10
3.5%
|
9
3.1%
|
| Creatinine µmol/L, Low, Week 4, n=283, 279 |
19
6.6%
|
10
3.5%
|
| Creatinine µmol/L, High, Week 4, n=283, 279 |
6
2.1%
|
3
1%
|
| Creatinine µmol/L, Low, Week 8, n=282, 275 |
20
7%
|
10
3.5%
|
| Creatinine µmol/L, High, Week 8, n=282, 275 |
7
2.4%
|
5
1.7%
|
| GGT U/L, Low, Week 4, n=283, 279 |
8
2.8%
|
3
1%
|
| GGT U/L, High, Week 4, n=283, 279 |
4
1.4%
|
3
1%
|
| GGT U/L, Low, Week 8, n=282, 275 |
10
3.5%
|
6
2.1%
|
| GGT U/L, High, Week 8, n=282, 275 |
4
1.4%
|
9
3.1%
|
| Glucose mmol/L, Low, Week 4, n=283, 279 |
17
5.9%
|
14
4.9%
|
| Glucose mmol/L, High, Week 4, n=283, 279 |
16
5.6%
|
31
10.8%
|
| Glucose mmol/L, Low, Week 8, n=282, 275 |
16
5.6%
|
16
5.6%
|
| Glucose mmol/L, High, Week 8, n=282, 275 |
21
7.3%
|
12
4.2%
|
| Potassium mmol/L, Low, Week 4, n=283, 279 |
3
1%
|
2
0.7%
|
| Potassium mmol/L, High, Week 4, n=283, 279 |
1
0.3%
|
1
0.3%
|
| Potassium mmol/L, Low, Week 8, n=282, 275 |
1
0.3%
|
2
0.7%
|
| Potassium mmol/L, High, Week 8, n=282, 275 |
2
0.7%
|
1
0.3%
|
| Magnesium mmol/L, Low, Week 4, n=283, 279 |
0
0%
|
0
0%
|
| Magnesium mmol/L, High, Week 4, n=283, 279 |
0
0%
|
2
0.7%
|
| Magnesium mmol/L, Low, Week 8, n=282, 275 |
0
0%
|
1
0.3%
|
| Magnesium mmol/L, High, Week 8, n=282, 275 |
0
0%
|
0
0%
|
| Protein g/L, Low, Week 4, n=283, 279 |
16
5.6%
|
17
5.9%
|
| Protein g/L, High, Week 4, n=283, 279 |
1
0.3%
|
2
0.7%
|
| Protein g/L, Low, Week 8, n=282, 275 |
16
5.6%
|
9
3.1%
|
| Protein g/L, High, Week 8, n=282, 275 |
4
1.4%
|
2
0.7%
|
| Sodium mmol/L, Low, Week 4, n=283, 279 |
3
1%
|
6
2.1%
|
| Sodium mmol/L, High, Week 4, n=283, 279 |
1
0.3%
|
1
0.3%
|
| Sodium mmol/L, Low, Week 8, n=282, 275 |
5
1.7%
|
6
2.1%
|
| Sodium mmol/L, High, Week 8, n=282, 275 |
2
0.7%
|
1
0.3%
|
| Urate µmol/L, Low, Week 4, n=283, 279 |
5
1.7%
|
5
1.7%
|
| Urate µmol/L, High, Week 4, n=283, 279 |
4
1.4%
|
5
1.7%
|
| Urate µmol/L, Low, Week 8, n=282, 275 |
9
3.1%
|
7
2.4%
|
| Urate µmol/L, High, Week 8, n=282, 275 |
4
1.4%
|
4
1.4%
|
| UN mmol/L, Low, Week 4, n=283, 279 |
3
1%
|
4
1.4%
|
| UN mmol/L, High, Week 4, n=283, 279 |
9
3.1%
|
7
2.4%
|
| UN mmol/L, Low, Week 8, n=282, 275 |
3
1%
|
6
2.1%
|
| UN mmol/L, High, Week 8, n=282, 275 |
8
2.8%
|
7
2.4%
|
| Title | Number of Participants With Urinalysis Parameters |
|---|---|
| Description | Urinalysis parameters included amorphous crystals, bacteria, bilirubin, calcium oxalate (Ca Ox) crystals, choriogonadotropin beta, clarity, color, crystals of Ca Ox, erythrocytes, glucose, hemoglobin, ketone bodies, ketones, leukocyte cell clumps, leukocyte esterase, leukocytes, mucous threads, nitrite, occult blood, protein, specific gravity, squamous epithelial cells, turbidity, urobilinogen, and transitional epithelial cells. In urinalysis test plus sign (+) indicates increase in the level of the parameters. |
| Time Frame | Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | AVA Alone | AVA+Raxibacumab |
|---|---|---|
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. |
| Measure Participants | 286 | 280 |
| Amorphous crystals 1+ |
1
0.3%
|
5
1.7%
|
| Amorphous crystals 2+ |
7
2.4%
|
1
0.3%
|
| Amorphous crystals 3+ |
0
0%
|
3
1%
|
| Amorphous crystals 4+ |
3
1%
|
4
1.4%
|
| Amorphous crystals trace |
1
0.3%
|
2
0.7%
|
| Bacteria 1+ |
1
0.3%
|
2
0.7%
|
| Bacteria 2+ |
2
0.7%
|
1
0.3%
|
| Bacteria 3+ |
0
0%
|
1
0.3%
|
| Bacteria 4+ |
1
0.3%
|
0
0%
|
| Bacteria few |
2
0.7%
|
1
0.3%
|
| Bacteria many |
1
0.3%
|
0
0%
|
| Bacteria mod |
1
0.3%
|
2
0.7%
|
| Bacteria Occ |
3
1%
|
7
2.4%
|
| Bacteria rare |
5
1.7%
|
8
2.8%
|
| Bacteria trace |
2
0.7%
|
3
1%
|
| Bilirubin 1+ |
2
0.7%
|
3
1%
|
| Bilirubin negative |
196
68.3%
|
188
65.7%
|
| Bilirubin small |
0
0%
|
2
0.7%
|
| Ca Ox Crystals few |
0
0%
|
2
0.7%
|
| Ca Ox Crystals rare |
2
0.7%
|
3
1%
|
| Choriogonadotropin Beta negative |
24
8.4%
|
16
5.6%
|
| Choriogonadotropin Beta positive |
1
0.3%
|
0
0%
|
| Clarity, clear |
38
13.2%
|
44
15.4%
|
| Clarity, cloudy |
8
2.8%
|
2
0.7%
|
| Clarity turbid |
1
0.3%
|
0
0%
|
| Color amber |
2
0.7%
|
5
1.7%
|
| Color colorless |
1
0.3%
|
1
0.3%
|
| Color light-red |
0
0%
|
1
0.3%
|
| Color light-yellow |
6
2.1%
|
2
0.7%
|
| Color yellow |
74
25.8%
|
71
24.8%
|
| Crystals Ca-Ox |
9
3.1%
|
17
5.9%
|
| Erythrocytes 0-2 |
107
37.3%
|
104
36.4%
|
| Erythrocytes 10-25 |
3
1%
|
0
0%
|
| Erythrocytes 2-5 |
2
0.7%
|
6
2.1%
|
| Erythrocytes 25-50 |
0
0%
|
1
0.3%
|
| Erythrocytes 5-10 |
1
0.3%
|
2
0.7%
|
| Erythrocytes 50-99 |
1
0.3%
|
0
0%
|
| Erythrocytes innumerable |
0
0%
|
1
0.3%
|
| Erythrocytes less than 1 |
10
3.5%
|
4
1.4%
|
| Erythrocytes Tntc |
1
0.3%
|
0
0%
|
| Glucose positive |
1
0.3%
|
0
0%
|
| Glucose negative |
257
89.5%
|
257
89.9%
|
| Hemoglobin + |
13
4.5%
|
18
6.3%
|
| Hemoglobin ++ |
0
0%
|
3
1%
|
| Hemoglobin +++ |
1
0.3%
|
2
0.7%
|
| Hemoglobin large |
4
1.4%
|
2
0.7%
|
| Hemoglobin mod |
3
1%
|
6
2.1%
|
| Hemoglobin negative |
174
60.6%
|
166
58%
|
| Hemoglobin small |
13
4.5%
|
13
4.5%
|
| Hemoglobin trace |
2
0.7%
|
1
0.3%
|
| Ketone bodies negative |
114
39.7%
|
106
37.1%
|
| Ketone bodies trace |
0
0%
|
4
1.4%
|
| Ketones + |
1
0.3%
|
1
0.3%
|
| Ketones ++ |
1
0.3%
|
0
0%
|
| Ketones ++++ |
0
0%
|
2
0.7%
|
| Ketones mod |
1
0.3%
|
0
0%
|
| Ketones negative |
255
88.9%
|
247
86.4%
|
| Ketones trace |
0
0%
|
7
2.4%
|
| Leukocyte Cell Clumps Occ |
1
0.3%
|
0
0%
|
| Leukocyte Cell Clumps rare |
1
0.3%
|
1
0.3%
|
| Leukocyte Esterase 1+ |
4
1.4%
|
2
0.7%
|
| Leukocyte Esterase 2+ |
1
0.3%
|
1
0.3%
|
| Leukocyte Esterase 3+ |
1
0.3%
|
0
0%
|
| Leukocyte Esterase large |
10
3.5%
|
7
2.4%
|
| Leukocyte Esterase Mod |
1
0.3%
|
3
1%
|
| Leukocyte Esterase Moderate |
1
0.3%
|
4
1.4%
|
| Leukocyte Esterase negative |
162
56.4%
|
159
55.6%
|
| Leukocyte Esterase small |
5
1.7%
|
7
2.4%
|
| Leukocyte Esterase trace |
13
4.5%
|
10
3.5%
|
| Leukocyte + |
5
1.7%
|
0
0%
|
| Leukocyte ++ |
1
0.3%
|
0
0%
|
| Leukocyte +++ |
1
0.3%
|
1
0.3%
|
| Leukocyte 0-2 |
105
36.6%
|
99
34.6%
|
| Leukocyte 10-25 |
2
0.7%
|
2
0.7%
|
| Leukocyte 2-5 |
6
2.1%
|
7
2.4%
|
| Leukocyte 25-50 |
0
0%
|
1
0.3%
|
| Leukocyte 5-10 |
2
0.7%
|
4
1.4%
|
| Leukocyte less than 1 |
8
2.8%
|
5
1.7%
|
| Leukocyte large |
4
1.4%
|
5
1.7%
|
| Leukocyte mod |
1
0.3%
|
5
1.7%
|
| Leukocyte negative |
187
65.2%
|
188
65.7%
|
| Leukocyte small |
2
0.7%
|
5
1.7%
|
| Leukocyte trace |
9
3.1%
|
7
2.4%
|
| Mucous threads 2+ |
0
0%
|
1
0.3%
|
| Mucous Threads few |
24
8.4%
|
25
8.7%
|
| Mucous Threads many |
2
0.7%
|
1
0.3%
|
| Mucous Threads Mod |
1
0.3%
|
2
0.7%
|
| Mucous Threads trace |
1
0.3%
|
2
0.7%
|
| Nitrite negative |
190
66.2%
|
190
66.4%
|
| Nitrite positive |
8
2.8%
|
3
1%
|
| Occult Blood 1+ |
1
0.3%
|
0
0%
|
| Occult Blood 2+ |
1
0.3%
|
2
0.7%
|
| Occult Blood 3+ |
0
0%
|
1
0.3%
|
| Occult Blood large |
5
1.7%
|
3
1%
|
| Occult Blood mod |
1
0.3%
|
5
1.7%
|
| Occult Blood moderate |
2
0.7%
|
7
2.4%
|
| Occult Blood negative |
163
56.8%
|
148
51.7%
|
| Occult Blood small |
22
7.7%
|
21
7.3%
|
| Occult Blood trace |
3
1%
|
6
2.1%
|
| Protein + |
7
2.4%
|
10
3.5%
|
| Protein ++ |
2
0.7%
|
0
0%
|
| Protein ++++ |
0
0%
|
1
0.3%
|
| Protein 1+ |
3
1%
|
4
1.4%
|
| Protein large |
1
0.3%
|
0
0%
|
| Protein negative |
244
85%
|
238
83.2%
|
| Protein non-heam |
1
0.3%
|
0
0%
|
| Protein trace |
12
4.2%
|
15
5.2%
|
| Specific Gravity <=1.005 |
1
0.3%
|
5
1.7%
|
| Specific Gravity >=1.030 |
3
1%
|
6
2.1%
|
| Squamous Epithelial Cells 0-2 |
8
2.8%
|
3
1%
|
| Squamous Epithelial Cells 2-5 |
2
0.7%
|
5
1.7%
|
| Squamous Epithelial Cells 5-10 |
2
0.7%
|
2
0.7%
|
| Squamous Epithelial Cells <1 |
9
3.1%
|
8
2.8%
|
| Turbidity clear |
15
5.2%
|
15
5.2%
|
| Turbidity cloudy |
2
0.7%
|
3
1%
|
| Turbidity hazy |
19
6.6%
|
16
5.6%
|
| Urobilinogen <2.0 |
113
39.4%
|
111
38.8%
|
| Urobilinogen less than 2.0 |
33
11.5%
|
31
10.8%
|
| Urobilinogen normal |
47
16.4%
|
46
16.1%
|
| Transitional Epithelial Cells <1 |
2
0.7%
|
0
0%
|
Adverse Events
| Time Frame | On-treatment SAEs and non-serious AEs were collected from the start of investigational product until Day 183. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Population | |||||
| Arm/Group Title | AVA Alone | Raxibacumab Only and Discontinued Due to AE During Raxibacumab Infusion | AVA + Raxibacumab With no AE During Raxibacumab Infusion That Led to Discontinuation | |||
| Arm/Group Description | Participants administered AVA SC, 0.5 mL on Days 1, 15 and 29 | During the study, six of 286 raxibacumab-treated subjects (2.1%) had adverse events (AEs) to raxibacumab that required drug discontinuation, administration of additional medications for mitigation of signs and symptoms, and discontinuation from the study. This new arm is included to capture safety data for these 6 subjects. | Participants administered SC 0.5 mL of AVA doses on Days 1, 15, and 29, with the first AVA dose administered immediately after completion of a single 40 mg/kg, IV infusion of raxibacumab dose (Day 1). Participants were premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions. | |||
All Cause Mortality |
||||||
| AVA Alone | Raxibacumab Only and Discontinued Due to AE During Raxibacumab Infusion | AVA + Raxibacumab With no AE During Raxibacumab Infusion That Led to Discontinuation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
Serious Adverse Events |
||||||
| AVA Alone | Raxibacumab Only and Discontinued Due to AE During Raxibacumab Infusion | AVA + Raxibacumab With no AE During Raxibacumab Infusion That Led to Discontinuation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/286 (1.7%) | 0/6 (0%) | 3/280 (1.1%) | |||
| Hepatobiliary disorders | ||||||
| Bile Duct Stone | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Cholecystitis | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Cholelithiasis | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Infections and infestations | ||||||
| Bronchitis | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Toxicity To Various Agents | 1/286 (0.3%) | 1/6 (16.7%) | 0/280 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Rhabdomyolysis | 1/286 (0.3%) | 1/6 (16.7%) | 0/280 (0%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion Spontaneous | 2/286 (0.7%) | 2/6 (33.3%) | 0/280 (0%) | |||
| Psychiatric disorders | ||||||
| Completed Suicide | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Suicidal Ideation | 1/286 (0.3%) | 1/6 (16.7%) | 0/280 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asphyxia | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Respiratory Failure | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| AVA Alone | Raxibacumab Only and Discontinued Due to AE During Raxibacumab Infusion | AVA + Raxibacumab With no AE During Raxibacumab Infusion That Led to Discontinuation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 85/286 (29.7%) | 6/6 (100%) | 80/280 (28.6%) | |||
| Blood and lymphatic system disorders | ||||||
| Leukocytosis | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Ear and labyrinth disorders | ||||||
| Ear Discomfort | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Eye disorders | ||||||
| Visual Impairment | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 6/286 (2.1%) | 0/6 (0%) | 4/280 (1.4%) | |||
| Vomiting | 2/286 (0.7%) | 0/6 (0%) | 2/280 (0.7%) | |||
| Toothache | 2/286 (0.7%) | 0/6 (0%) | 0/280 (0%) | |||
| Abdominal Discomfort | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Abdominal Pain Lower | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Abdominal Pain Upper | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Diarrhoea | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Gastritis | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Gastrooesophageal Reflux Disease | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Rectal Haemorrhage | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| General disorders | ||||||
| Injection Site Reaction | 18/286 (6.3%) | 0/6 (0%) | 18/280 (6.4%) | |||
| Injection Site Erythema | 11/286 (3.8%) | 0/6 (0%) | 13/280 (4.6%) | |||
| Injection Site Pain | 6/286 (2.1%) | 0/6 (0%) | 8/280 (2.9%) | |||
| Injection Site Swelling | 4/286 (1.4%) | 0/6 (0%) | 3/280 (1.1%) | |||
| Injection Site Pruritus | 4/286 (1.4%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Fatigue | 3/286 (1%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Injection Site Nodule | 1/286 (0.3%) | 0/6 (0%) | 2/280 (0.7%) | |||
| Feeling hot | 2/286 (0.7%) | 0/6 (0%) | 0/280 (0%) | |||
| Pain | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Pyrexia | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Asthenia | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Catheter Site Pain | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Chest Discomfort | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Induration | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Infusion Site Bruising | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Infusion Site Extravasation | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Injection Site Mass | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Injection Site Rash | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Local Swelling | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Peripheral Swelling | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Vaccination Site Reaction | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Immune system disorders | ||||||
| Seasonal Allergy | 3/286 (1%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Hypersensitivity | 0/286 (0%) | 1/6 (16.7%) | 0/280 (0%) | |||
| Infections and infestations | ||||||
| Urinary Tract Infection | 6/286 (2.1%) | 0/6 (0%) | 2/280 (0.7%) | |||
| Upper Respiratory Tract Infection | 3/286 (1%) | 0/6 (0%) | 4/280 (1.4%) | |||
| Bronchitis | 2/286 (0.7%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Viral Upper Respiratory Tract Infection | 3/286 (1%) | 0/6 (0%) | 0/280 (0%) | |||
| Influenza | 2/286 (0.7%) | 0/6 (0%) | 0/280 (0%) | |||
| Pharyngitis Streptococcal | 2/286 (0.7%) | 0/6 (0%) | 0/280 (0%) | |||
| Sinusitis | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Tooth Infection | 2/286 (0.7%) | 0/6 (0%) | 0/280 (0%) | |||
| Acute Sinusitis | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Conjunctivitis | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Furuncle | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Tonsillitis | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Tooth Abscess | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Ligament Sprain | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Muscle Strain | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Animal Bite | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Arthropod Bite | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Contusion | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Foot Fracture | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Infusion Related Reaction | 0/286 (0%) | 4/6 (66.7%) | 1/280 (0.4%) | |||
| Laceration | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Limb Injury | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Road Traffic Accident | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Skin Injury | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Upper Limb Fracture | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Investigations | ||||||
| Aspartate Aminotransferase Increased | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Blood Creatine Phosphokinase Increased | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Hepatic Enzyme Increased | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Lymphocyte Count Decreased | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Neutrophil Count Decreased | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Pain In Extremity | 3/286 (1%) | 0/6 (0%) | 3/280 (1.1%) | |||
| Back Pain | 2/286 (0.7%) | 0/6 (0%) | 2/280 (0.7%) | |||
| Arthralgia | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Muscle Tightnes | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Flank Pain | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Muscle Fatigue | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Muscular Weakness | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Musculoskeletal Chest Pain | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Myalgia | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Nervous system disorders | ||||||
| Headache | 6/286 (2.1%) | 0/6 (0%) | 9/280 (3.2%) | |||
| Presyncope | 1/286 (0.3%) | 0/6 (0%) | 3/280 (1.1%) | |||
| Nerve Compression | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Paraesthesia | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Dizziness | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Dysgeusia | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Hypoaesthesia | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Psychiatric disorders | ||||||
| Loss Of Libido | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Anxiety | 0/286 (0%) | 0/6 (0%) | 0/280 (0%) | |||
| Renal and urinary disorders | ||||||
| Nephrolithiasis | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Nasal Congestion | 2/286 (0.7%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Cough | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Sinus Congestion | 2/286 (0.7%) | 0/6 (0%) | 0/280 (0%) | |||
| Dry Throat | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Oropharyngeal Pain | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Respiratory Tract Congestion | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Rhinorrhoea | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Throat Tightness | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis Contact | 2/286 (0.7%) | 0/6 (0%) | 0/280 (0%) | |||
| Erythema | 1/286 (0.3%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Urticaria | 0/286 (0%) | 1/6 (16.7%) | 2/280 (0.7%) | |||
| Dermatitis | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Hyperhidrosis | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Miliaria | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Pruritus | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Pruritus Generalised | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Rash Erythematous | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
| Rash Generalised | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Vascular disorders | ||||||
| Haematoma | 0/286 (0%) | 0/6 (0%) | 3/280 (1.1%) | |||
| Flushing | 1/286 (0.3%) | 0/6 (0%) | 0/280 (0%) | |||
| Hot Flush | 0/286 (0%) | 0/6 (0%) | 1/280 (0.4%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
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