Glomerular Disease, IgAN, Immunoglobulin A Nephropathy
Conditions
Keywords
VIS649, Kidney Diseases, Glomerulonephritis, IGA, Glomerulonephritis, Nephritis, Autoimmune Diseases, Immune System Diseases, Immunoglobulins, Antibodies, Immunoglobulin A, Immunologic Factors, Physiological Effects of Drugs, Proteinuria
Brief summary
The purpose of this study is to evaluate the efficacy and safety of VIS649 in participants with immunoglobulin A (IgA) Nephropathy (IgAN)
Detailed description
This is a Phase 2, double-blind, randomized, placebo-controlled study in patients aged 18 years and above with biopsy confirmed diagnosis of IgAN. The study is designed to test the safety and effectiveness of multiple doses of VIS649. The main objectives are to evaluate the safety and tolerability of VIS649 and to evaluate the dose response of different doses of VIS649 by measuring proteinuria. The study is comprised of three main periods, Screening, Treatment (12 months) and Follow-Up (4 months). Approximately 144 patients will be enrolled. The findings from this study will form the basis for subsequent clinical development of VIS649. VIS649 is a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of the cytokine A PRoliferation Inducing Ligand (APRIL), a key factor in the production of aberrantly glycosylated IgA1 (a-g- IgA1), which is critical to the pathogenesis of IgAN.
Interventions
DRUGDose-Placebo
Unit Dose Strength - 0.9%.
DRUGLow Dose-VIS649
Dose Level = Low
DRUGMedium Dose-VIS649
Dose Level = Medium
DRUGHigh Dose-VIS649
Dose Level = High
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patient, Investigator, Care Provider, Outcomes Assessor
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant is a male or female ≥ 18 years of age at the time of signing the informed consent. 2. Participant must have biopsy-confirmed IgAN. 3. Participant has medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per local SOC and applicable guidelines, for at least 3 months preceding screening. Participants should optimally be on at least 50% of the maximum recommended dose of these agents; however, if a participant is on their maximally tolerated dose (and this is \< 50% of the maximum recommended dose) and has been on this dose for at least 3 months, they may be enrolled. Participants who are unable to tolerate ACEI/ARB therapy may be eligible for participation in the study if their overall management of IgAN, including BP control, is as per local SOC and applicable guidelines. 4. Participants must have screening uPCR ≥ 0.75 g/g measured from a 24-hour urine or 24-hour urine protein ≥ 1.0 g/d, as measured from 24-hour urine collection. The proteinuria should be assessed when the participant is considered to be in a steady state with no recent heavy exercise, fever, or other potential issues that could impact the result. 5. Participants must have eGFR ≥ 45 mL/min/1.73 m² using the CKD-EPI formula. 6. Participant's serum Ig values must meet specified criteria 7. Female participants of childbearing potential must have a negative serum pregnancy test prior to the first dose. 8. Participant is willing to adhere to contraceptive requirements. 9. Participant or a legally authorized representative is able and is willing to give voluntary written informed consent
Exclusion criteria
Participants are excluded from the study if they meet any of the following criteria: 1. Participant has secondary forms of IgAN as defined by the treating physician. 2. Participant has co-existing CKD, other than IgAN. 3. Participant has evidence of additional pathological findings in the kidney biopsy (eg, diabetic kidney disease, membranous nephropathy, or lupus nephritis). However, hypertensive vascular changes are acceptable. 4. Participant has kidney biopsy MEST or MEST-C score as defined in the protocol. 5. Participant has nephrotic syndrome. 6. Participant has received a solid organ transplant, including kidney. 7. Participant has received bone marrow or hematologic stem cell transplantation. 8. Participant is currently receiving systemic immunosuppression (excluding topical, ophthalmic, per rectum, or inhaled corticosteroids). 9. Participant has received treatment with systemic corticosteroid therapy within 16 weeks of initial screening. 10. Participant has received treatment with a systemic immunosuppressive agents within 16 weeks of initial screening. 11. Participant has any chronic infectious disease. 12. Participant has acute infectious disease at the time of screening. 13. Participant has Type 1 diabetes. 14. Participant has uncontrolled Type 2 diabetes, as evidenced by a screening hemoglobin A1c value \> 8%. 15. Participant has uncontrolled BP (\> 140 mm Hg systolic or \> 90 mm Hg diastolic) 16. Participant has a history of chronic autoimmune neurodegenerative disorder such as multiple sclerosis. 17. Participant has a known allergy or intolerance to any component of the study intervention. 18. Participant is breastfeeding. 19. Participant has poorly compensated or controlled ischemic heart disease or cardiomyopathy, as judged by the Investigator. 20. Participant has chronic obstructive pulmonary disease (COPD) or asthma that has required systemic steroid therapy during the prior year. 21. Participant has known cirrhosis or liver dysfunction, defined as presence of coagulopathy, platelet count \< 100,000/μL or alanine aminotransferase \> 3× upper limit of normal. 22. Participant has active malignancy or is receiving chemotherapy for malignancy, except for nonmelanoma skin cancers and cervical carcinoma in situ. Participants with prior malignancy who have been documented to be cancer-free for ≥ 5 years may be enrolled. 23. Participant is planning or scheduled to undergo a tonsillectomy. Prior tonsillectomy is acceptable (if greater than 6 months prior to screening). 24. Participant enrolled in another investigational drug or device study within 3 months prior to initial screening. 25. Participant with a pre-existing illness other than those listed above that, in the opinion of the Investigator, would place the participant at increased risk through participation in this study. 26. Participant is unable to comply with study protocol procedures and/or study visit schedules. 27. Participant with known or suspected alcohol or drug abuse that would compromise their safety or study participation of the participant, in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Graded by Severity | Baseline to End of Study (16 months) | The number of participants who experienced adverse events, graded by maximum severity, are presented. |
| Changes From Baseline in Clinical Laboratory Tests | Baseline to End of Study (16 months) | The number of participants who experience a shift from normal at baseline to Grade 3/4 (moderate/sever) at a postbaseline time point are presented. |
| Clinically Meaningful Changes From Baseline in Vital Signs | Baseline to End of Study (16 months) | The number of participants who experienced clinically meaningful changes from baseline in vital signs (body mass index, diastolic blood pressure, height, heart rate, mean arterial pressure, respiratory rate, systolic blood pressure, temperature, and weight) are presented. |
| Clinically Significant Physical Examinations | Baseline to End of Study (16 months) | Clinically significant physical examination findings are presented. |
| Change From Baseline in uPCR: Month 12 | 12 months | Natural Log 24-Hour uPCR (Schedule A Urine Collection) Change from Baseline at Month 12: mixed model with repeated measurements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in uPCR: Months 9 and 16 | Baseline to 9 months and 16 months (16 months total) | Change from baseline in uPCR (Urine protein/creatinine ratio) |
| Change in 24-hour Urine Protein Excretion: Months 12 and 16 | 16 months | Change in 24-hour urine protein excretion from baseline to Months 12 and 16 |
| Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Baseline to 9,12, and 16 months (16 months total) | Number of participants in each group achieving a greater than or equal to 30% decline from baseline in urinary protein/creatinine ratio (uPCR) at Months 9, 12, and 16 |
| Participants in Each Group Achieving Clinical Remission | Baseline to End of Study (16 months) | Number of participants in each group achieving clinical remission. Clinical remission was defined as reduction in 24-hour urine protein excretion to less than 300 mg/day for at least 3 consecutive months. |
| Change From Baseline in eGFR at Months 9, 12, and 16 | Baseline to 12 and 16 months | Change from baseline in (eGFR) at Months 9, 12, and 16 |
| Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | Baseline to 12 and 16 months | Percent change from baseline in total serum immunoglobin (Ig)A, IgG, and IgM concentrations at Months 12 and 16 in PD population |
| Mean Serum PK Parameters at Month 0 and Month 11: Cmax | Months 0 and 11 | Serum PK parameters: maximum serum concentration (Cmax) |
| Median Serum PK Parameters at Month 0 and Month 11: Tmax | Month 0 and Month 11 | Serum PK parameters: time of maximum serum concentration (Tmax) |
| Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30 | Month 0 | Serum PK parameters of area under the concentration-time curve from time 0 to infinity (AUC0-inf) and area under the concentration-time curve from time 0 to Day 30 (AUC0-30) |
| Mean Serum PK Parameters at Month 0 and Month 11: t1/2z | Month 0 and Month 11 | Serum PK parameters: terminal elimination half-life(t1/2z) |
| Median Serum PK Parameters at Month 0: CL | Month 0 | Serum PK parameters of clearance. 8 mg/kg was not reported for this outcome measure. Other arms were not provided due to participants meeting exclusion criteria: %AUCext \> 20% and R2 Adjusted \< 0.8. Affected parameters at participant visits meeting this criteria were excluded. |
| Mean Serum PK Parameters at Month 0: Vz | Month 0 | Serum PK parameters of apparent volume of distribution (Vz). 8 mg/kg was not reported for this outcome measure. Other arms were not provided due to participants meeting exclusion criteria: %AUCext \> 20% and R2 Adjusted \< 0.8. Affected parameters at participant visits meeting this criteria were excluded. |
| Mean Serum PK Parameters at Month 11: AUCτ | Month 11 | Serum PK parameters: area under the concentration-time curve from time 0 to the end of the dosing period (AUCτ) |
| Mean Serum PK Parameters at Month 11: Vss | Month 11 | Serum PK parameters: volume of distribution at steady-state (Vss) |
| Mean Serum PK Parameters at Month 11: CLss | Month 11 | Serum PK parameters: clearance at steady-state (CLss) |
| Mean Serum PK Parameters at Month 11: Rac[AUC0-30] | Month 11 | Serum PK parameters: accumulation ratio of area under the concentration-time curve from time 0 to infinity (Rac\[AUC0-30\]) |
Countries
Australia, Canada, Hong Kong, India, Japan, Malaysia, Philippines, Singapore, South Korea, Spain, Sri Lanka, Taiwan, Thailand, United Kingdom, United States
Contacts
STUDY_DIRECTORAsher Schachter, M.D.
Visterra, Inc.
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VIS649 2 mg/kg 2 mg/kg VIS649 administered intravenously | 38 |
| VIS649 4 mg/kg 4 mg/kg of VIS649 administered intravenously | 41 |
| VIS649 8 mg/kg 8 mg/kg of VIS649 administered intravenously | 38 |
| Placebo Placebo administered intravenously | 38 |
| Total | 155 |
Baseline characteristics
| Characteristic | VIS649 2 mg/kg | Total | Placebo | VIS649 8 mg/kg | VIS649 4 mg/kg |
|---|---|---|---|---|---|
| ACEI or ARB Therapy | 37 Participants | 152 Participants | 38 Participants | 37 Participants | 40 Participants |
| Age, Continuous | 41.0 Years | 39.0 Years | 36.5 Years | 41.5 Years | 39.0 Years |
| Baseline 24-hour uPCR | 1.46 urinary protein/creatinine ratio STANDARD_DEVIATION 0.123 | 1.52 urinary protein/creatinine ratio STANDARD_DEVIATION 0.069 | 1.68 urinary protein/creatinine ratio STANDARD_DEVIATION 0.175 | 1.44 urinary protein/creatinine ratio STANDARD_DEVIATION 0.137 | 1.53 urinary protein/creatinine ratio STANDARD_DEVIATION 0.123 |
| Baseline urinary protein excretion (mg/day) | 1470.50 mg per day | 1900 mg per day | 2133.50 mg per day | 1900.00 mg per day | 1927.00 mg per day |
| Body Mass Index (BMI) | 27.15 kg/m2 STANDARD_DEVIATION 4.529 | 27.56 kg/m2 STANDARD_DEVIATION 5.894 | 27.35 kg/m2 STANDARD_DEVIATION 6.749 | 27.57 kg/m2 STANDARD_DEVIATION 5.778 | 28.10 kg/m2 STANDARD_DEVIATION 6.424 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 9 Participants | 2 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 144 Participants | 35 Participants | 35 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Height | 165.87 Centimeters STANDARD_DEVIATION 8.919 | 165.22 Centimeters STANDARD_DEVIATION 10.12 | 161.84 Centimeters STANDARD_DEVIATION 10.794 | 165.48 Centimeters STANDARD_DEVIATION 10.277 | 167.50 Centimeters STANDARD_DEVIATION 9.933 |
| History of Hypertension | 29 Participants | 112 Participants | 24 Participants | 28 Participants | 31 Participants |
| Previous use of systemic immunosuppressive therapy | 14 Participants | 36 Participants | 7 Participants | 8 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 115 Participants | 28 Participants | 28 Participants | 31 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 36 Participants | 10 Participants | 8 Participants | 9 Participants |
| Region of Enrollment Australia | 1 participants | 6 participants | 3 participants | 0 participants | 2 participants |
| Region of Enrollment Canada | 0 participants | 2 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Hong Kong | 3 participants | 5 participants | 2 participants | 0 participants | 0 participants |
| Region of Enrollment India | 5 participants | 39 participants | 14 participants | 10 participants | 10 participants |
| Region of Enrollment Japan | 5 participants | 19 participants | 4 participants | 5 participants | 5 participants |
| Region of Enrollment Malaysia | 3 participants | 8 participants | 1 participants | 2 participants | 2 participants |
| Region of Enrollment Philippines | 1 participants | 4 participants | 0 participants | 1 participants | 2 participants |
| Region of Enrollment Singapore | 1 participants | 6 participants | 0 participants | 2 participants | 3 participants |
| Region of Enrollment South Korea | 2 participants | 15 participants | 4 participants | 5 participants | 4 participants |
| Region of Enrollment Spain | 2 participants | 9 participants | 3 participants | 1 participants | 3 participants |
| Region of Enrollment Sri Lanka | 2 participants | 5 participants | 1 participants | 1 participants | 1 participants |
| Region of Enrollment Taiwan | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment Thailand | 4 participants | 10 participants | 2 participants | 1 participants | 3 participants |
| Region of Enrollment United Kingdom | 1 participants | 5 participants | 2 participants | 2 participants | 0 participants |
| Region of Enrollment United States | 8 participants | 21 participants | 2 participants | 6 participants | 5 participants |
| Sex: Female, Male Female | 16 Participants | 67 Participants | 24 Participants | 12 Participants | 15 Participants |
| Sex: Female, Male Male | 22 Participants | 88 Participants | 14 Participants | 26 Participants | 26 Participants |
| SGLT2i use at baseline | 3 Participants | 9 Participants | 3 Participants | 1 Participants | 2 Participants |
| Time since biopsy | 781.0 Days | 565.0 Days | 933.0 Days | 364.0 Days | 288.0 Days |
| Weight | 74.97 Kilograms STANDARD_DEVIATION 15.031 | 75.59 Kilograms STANDARD_DEVIATION 19.323 | 72.40 Kilograms STANDARD_DEVIATION 21.124 | 75.54 Kilograms STANDARD_DEVIATION 19.237 | 79.18 Kilograms STANDARD_DEVIATION 21.216 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 41 | 0 / 38 | 1 / 38 |
| other Total, other adverse events | 28 / 38 | 33 / 41 | 31 / 38 | 27 / 38 |
| serious Total, serious adverse events | 2 / 38 | 2 / 41 | 1 / 38 | 2 / 38 |
Outcome results
Primary
Change From Baseline in uPCR: Month 12
Natural Log 24-Hour uPCR (Schedule A Urine Collection) Change from Baseline at Month 12: mixed model with repeated measurements
Time frame: 12 months
Population: modified intent-to-treat (mITT) Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VIS649 2 mg/kg | Change From Baseline in uPCR: Month 12 | -0.64 g/g | Standard Error 0.2 |
| VIS649 4 mg/kg | Change From Baseline in uPCR: Month 12 | -0.89 g/g | Standard Error 0.1 |
| VIS649 8 mg/kg | Change From Baseline in uPCR: Month 12 | -0.97 g/g | Standard Error 0.2 |
| Placebo | Change From Baseline in uPCR: Month 12 | -0.22 g/g | Standard Error 0.2 |
Primary
Changes From Baseline in Clinical Laboratory Tests
The number of participants who experience a shift from normal at baseline to Grade 3/4 (moderate/sever) at a postbaseline time point are presented.
Time frame: Baseline to End of Study (16 months)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS649 2 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Calcium | 1 Participants |
| VIS649 2 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Potassium | 2 Participants |
| VIS649 2 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Phosphate | 1 Participants |
| VIS649 2 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Sodium | 0 Participants |
| VIS649 2 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Triglycerides | 0 Participants |
| VIS649 2 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Hemoglobin | 0 Participants |
| VIS649 4 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Hemoglobin | 0 Participants |
| VIS649 4 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Sodium | 1 Participants |
| VIS649 4 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Calcium | 0 Participants |
| VIS649 4 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Phosphate | 0 Participants |
| VIS649 4 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Potassium | 1 Participants |
| VIS649 4 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Triglycerides | 1 Participants |
| VIS649 8 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Potassium | 1 Participants |
| VIS649 8 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Phosphate | 0 Participants |
| VIS649 8 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Sodium | 0 Participants |
| VIS649 8 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Hemoglobin | 1 Participants |
| VIS649 8 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Triglycerides | 0 Participants |
| VIS649 8 mg/kg | Changes From Baseline in Clinical Laboratory Tests | Calcium | 0 Participants |
| Placebo | Changes From Baseline in Clinical Laboratory Tests | Triglycerides | 0 Participants |
| Placebo | Changes From Baseline in Clinical Laboratory Tests | Hemoglobin | 0 Participants |
| Placebo | Changes From Baseline in Clinical Laboratory Tests | Potassium | 0 Participants |
| Placebo | Changes From Baseline in Clinical Laboratory Tests | Sodium | 0 Participants |
| Placebo | Changes From Baseline in Clinical Laboratory Tests | Calcium | 0 Participants |
| Placebo | Changes From Baseline in Clinical Laboratory Tests | Phosphate | 1 Participants |
Primary
Clinically Meaningful Changes From Baseline in Vital Signs
The number of participants who experienced clinically meaningful changes from baseline in vital signs (body mass index, diastolic blood pressure, height, heart rate, mean arterial pressure, respiratory rate, systolic blood pressure, temperature, and weight) are presented.
Time frame: Baseline to End of Study (16 months)
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIS649 2 mg/kg | Clinically Meaningful Changes From Baseline in Vital Signs | 0 Participants |
| VIS649 4 mg/kg | Clinically Meaningful Changes From Baseline in Vital Signs | 0 Participants |
| VIS649 8 mg/kg | Clinically Meaningful Changes From Baseline in Vital Signs | 0 Participants |
| Placebo | Clinically Meaningful Changes From Baseline in Vital Signs | 2 Participants |
Primary
Clinically Significant Physical Examinations
Clinically significant physical examination findings are presented.
Time frame: Baseline to End of Study (16 months)
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIS649 2 mg/kg | Clinically Significant Physical Examinations | 1 Participants |
| VIS649 4 mg/kg | Clinically Significant Physical Examinations | 0 Participants |
| VIS649 8 mg/kg | Clinically Significant Physical Examinations | 0 Participants |
| Placebo | Clinically Significant Physical Examinations | 0 Participants |
Primary
Number of Participants With Adverse Events Graded by Severity
The number of participants who experienced adverse events, graded by maximum severity, are presented.
Time frame: Baseline to End of Study (16 months)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading to trial drug interrupted | 5 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading to death | 0 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | Serious TEAE | 2 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of mild | 19 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | Serious TEAE related to trial drug | 0 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of severe | 2 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug | 7 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of moderate | 7 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading discontinuation of trial drug | 1 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Mild | 7 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Moderate | 0 Participants |
| VIS649 2 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Severe | 0 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of moderate | 9 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Severe | 0 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug | 7 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | Serious TEAE related to trial drug | 0 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading to trial drug interrupted | 1 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | Serious TEAE | 2 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of mild | 22 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Moderate | 0 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Mild | 7 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of severe | 2 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading to death | 0 Participants |
| VIS649 4 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading discontinuation of trial drug | 0 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | Serious TEAE | 1 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of mild | 22 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of moderate | 8 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of severe | 1 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug | 4 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Mild | 3 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Moderate | 1 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Severe | 0 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | Serious TEAE related to trial drug | 0 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading to trial drug interrupted | 3 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading discontinuation of trial drug | 0 Participants |
| VIS649 8 mg/kg | Number of Participants With Adverse Events Graded by Severity | TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Moderate | 0 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Mild | 5 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of mild | 23 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE leading to trial drug interrupted | 0 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug | 5 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of severe | 1 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE leading to death | 1 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE leading discontinuation of trial drug | 0 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | Serious TEAE | 2 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE related to trial drug with a maximum severity of Severe | 0 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | TEAE with a maximum severity of moderate | 3 Participants |
| Placebo | Number of Participants With Adverse Events Graded by Severity | Serious TEAE related to trial drug | 0 Participants |
Secondary
Change From Baseline in eGFR at Months 9, 12, and 16
Change from baseline in (eGFR) at Months 9, 12, and 16
Time frame: Baseline to 12 and 16 months
Population: modified intent-to-treat (mITT) Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS649 2 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 12 (Day 360) | -2.35 mL/min/1.73 m^2 | Standard Deviation 10.591 |
| VIS649 2 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 9 (Day 270) | -0.26 mL/min/1.73 m^2 | Standard Deviation 9.201 |
| VIS649 2 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 16 (Day 485) | -3.63 mL/min/1.73 m^2 | Standard Deviation 10.132 |
| VIS649 4 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 12 (Day 360) | 0.64 mL/min/1.73 m^2 | Standard Deviation 9.212 |
| VIS649 4 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 9 (Day 270) | 0.24 mL/min/1.73 m^2 | Standard Deviation 7.519 |
| VIS649 4 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 16 (Day 485) | -0.18 mL/min/1.73 m^2 | Standard Deviation 9.418 |
| VIS649 8 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 16 (Day 485) | -3.49 mL/min/1.73 m^2 | Standard Deviation 9.503 |
| VIS649 8 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 12 (Day 360) | -1.25 mL/min/1.73 m^2 | Standard Deviation 8.507 |
| VIS649 8 mg/kg | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 9 (Day 270) | 0.16 mL/min/1.73 m^2 | Standard Deviation 7.83 |
| Placebo | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 12 (Day 360) | -7.31 mL/min/1.73 m^2 | Standard Deviation 14.318 |
| Placebo | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 9 (Day 270) | -3.83 mL/min/1.73 m^2 | Standard Deviation 14.062 |
| Placebo | Change From Baseline in eGFR at Months 9, 12, and 16 | Month 16 (Day 485) | -8.54 mL/min/1.73 m^2 | Standard Deviation 14.36 |
Secondary
Change From Baseline in uPCR: Months 9 and 16
Change from baseline in uPCR (Urine protein/creatinine ratio)
Time frame: Baseline to 9 months and 16 months (16 months total)
Population: modified intent-to-treat (mITT) Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VIS649 2 mg/kg | Change From Baseline in uPCR: Months 9 and 16 | Month 9 | -0.70 g/g | Standard Error 0.2 |
| VIS649 2 mg/kg | Change From Baseline in uPCR: Months 9 and 16 | Month 16 | -0.45 g/g | Standard Error 0.2 |
| VIS649 4 mg/kg | Change From Baseline in uPCR: Months 9 and 16 | Month 16 | -0.87 g/g | Standard Error 0.2 |
| VIS649 4 mg/kg | Change From Baseline in uPCR: Months 9 and 16 | Month 9 | -0.85 g/g | Standard Error 0.1 |
| VIS649 8 mg/kg | Change From Baseline in uPCR: Months 9 and 16 | Month 16 | -1.04 g/g | Standard Error 0.2 |
| VIS649 8 mg/kg | Change From Baseline in uPCR: Months 9 and 16 | Month 9 | -0.99 g/g | Standard Error 0.1 |
| Placebo | Change From Baseline in uPCR: Months 9 and 16 | Month 9 | -0.17 g/g | Standard Error 0.2 |
| Placebo | Change From Baseline in uPCR: Months 9 and 16 | Month 16 | -0.11 g/g | Standard Error 0.2 |
Secondary
Change in 24-hour Urine Protein Excretion: Months 12 and 16
Change in 24-hour urine protein excretion from baseline to Months 12 and 16
Time frame: 16 months
Population: modified intent-to-treat (mITT) Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| VIS649 2 mg/kg | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 12 | 49.47 mg/day |
| VIS649 2 mg/kg | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 16 | 36.24 mg/day |
| VIS649 4 mg/kg | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 16 | 55.19 mg/day |
| VIS649 4 mg/kg | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 12 | 57.80 mg/day |
| VIS649 8 mg/kg | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 12 | 65.49 mg/day |
| VIS649 8 mg/kg | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 16 | 68.47 mg/day |
| Placebo | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 12 | 18.74 mg/day |
| Placebo | Change in 24-hour Urine Protein Excretion: Months 12 and 16 | Month 16 | 8.30 mg/day |
Secondary
Mean Serum PK Parameters at Month 0 and Month 11: Cmax
Serum PK parameters: maximum serum concentration (Cmax)
Time frame: Months 0 and 11
Population: Intensive Pharmacokinetic Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: Cmax | Month 0 | 78.78 μg/mL | Standard Deviation 16.69 |
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: Cmax | Month 11 | 65.45 μg/mL | Standard Deviation 21.83 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: Cmax | Month 0 | 128.88 μg/mL | Standard Deviation 38.52 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: Cmax | Month 11 | 185.63 μg/mL | Standard Deviation 54.29 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: Cmax | Month 0 | 245.75 μg/mL | Standard Deviation 46.35 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: Cmax | Month 11 | 939.13 μg/mL | Standard Deviation 1140.1 |
Secondary
Mean Serum PK Parameters at Month 0 and Month 11: t1/2z
Serum PK parameters: terminal elimination half-life(t1/2z)
Time frame: Month 0 and Month 11
Population: Intensive Pharmacokinetic Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: t1/2z | Month 11 | 8.82 days | Standard Deviation 2.89 |
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: t1/2z | Month 0 | 5.78 days | Standard Deviation 1.25 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: t1/2z | Month 11 | 10.67 days | Standard Deviation 2.66 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: t1/2z | Month 0 | 10.87 days | Standard Deviation 3.23 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: t1/2z | Month 0 | 18.64 days | Standard Deviation 5.26 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 0 and Month 11: t1/2z | Month 11 | 14.85 days | Standard Deviation 8.32 |
Secondary
Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30
Serum PK parameters of area under the concentration-time curve from time 0 to infinity (AUC0-inf) and area under the concentration-time curve from time 0 to Day 30 (AUC0-30)
Time frame: Month 0
Population: Intensive pharmacokinetic population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30 | AUC0-inf | 544.49 day∙μg/mL | Standard Deviation 191.8 |
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30 | AUC0-30 | 542.69 day∙μg/mL | Standard Deviation 167.88 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30 | AUC0-inf | 1189.68 day∙μg/mL | Standard Deviation 184.72 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30 | AUC0-30 | 1245.02 day∙μg/mL | Standard Deviation 311.85 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30 | AUC0-30 | 3019.78 day∙μg/mL | Standard Deviation 473.59 |
Secondary
Mean Serum PK Parameters at Month 0: Vz
Serum PK parameters of apparent volume of distribution (Vz). 8 mg/kg was not reported for this outcome measure. Other arms were not provided due to participants meeting exclusion criteria: %AUCext \> 20% and R2 Adjusted \< 0.8. Affected parameters at participant visits meeting this criteria were excluded.
Time frame: Month 0
Population: Intensive pharmacokinetic population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 0: Vz | 2056.05 mL | Standard Deviation 726.38 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 0: Vz | 4075.62 mL | Standard Deviation 1184.26 |
Secondary
Mean Serum PK Parameters at Month 11: AUCτ
Serum PK parameters: area under the concentration-time curve from time 0 to the end of the dosing period (AUCτ)
Time frame: Month 11
Population: Intensive Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 11: AUCτ | 555.17 day∙μg/mL | Standard Deviation 116.13 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 11: AUCτ | 2403.14 day∙μg/mL | Standard Deviation 929.12 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 11: AUCτ | 13057.23 day∙μg/mL | Standard Deviation 8432.07 |
Secondary
Mean Serum PK Parameters at Month 11: CLss
Serum PK parameters: clearance at steady-state (CLss)
Time frame: Month 11
Population: Intensive Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 11: CLss | 227.66 mL/day | Standard Deviation 50.99 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 11: CLss | 176.22 mL/day | Standard Deviation 69.07 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 11: CLss | 60.55 mL/day | Standard Deviation 25.82 |
Secondary
Mean Serum PK Parameters at Month 11: Rac[AUC0-30]
Serum PK parameters: accumulation ratio of area under the concentration-time curve from time 0 to infinity (Rac\[AUC0-30\])
Time frame: Month 11
Population: Intensive Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 11: Rac[AUC0-30] | 1.27 ratio | Standard Deviation 0.02 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 11: Rac[AUC0-30] | 2.01 ratio | Standard Deviation 0.63 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 11: Rac[AUC0-30] | 4.41 ratio | Standard Deviation 3.08 |
Secondary
Mean Serum PK Parameters at Month 11: Vss
Serum PK parameters: volume of distribution at steady-state (Vss)
Time frame: Month 11
Population: Intensive Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VIS649 2 mg/kg | Mean Serum PK Parameters at Month 11: Vss | 2998.81 mL/kg | Standard Deviation 1437.79 |
| VIS649 4 mg/kg | Mean Serum PK Parameters at Month 11: Vss | 2670.87 mL/kg | Standard Deviation 854.09 |
| VIS649 8 mg/kg | Mean Serum PK Parameters at Month 11: Vss | 2517.15 mL/kg | Standard Deviation 1529.85 |
Secondary
Median Serum PK Parameters at Month 0 and Month 11: Tmax
Serum PK parameters: time of maximum serum concentration (Tmax)
Time frame: Month 0 and Month 11
Population: Intensive Pharmacokinetic Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VIS649 2 mg/kg | Median Serum PK Parameters at Month 0 and Month 11: Tmax | Tmax: Month 0 | 0.052 days |
| VIS649 2 mg/kg | Median Serum PK Parameters at Month 0 and Month 11: Tmax | Tmax: Month 11 | 0.089 days |
| VIS649 4 mg/kg | Median Serum PK Parameters at Month 0 and Month 11: Tmax | Tmax: Month 0 | 0.052 days |
| VIS649 4 mg/kg | Median Serum PK Parameters at Month 0 and Month 11: Tmax | Tmax: Month 11 | 0.127 days |
| VIS649 8 mg/kg | Median Serum PK Parameters at Month 0 and Month 11: Tmax | Tmax: Month 0 | 0.125 days |
| VIS649 8 mg/kg | Median Serum PK Parameters at Month 0 and Month 11: Tmax | Tmax: Month 11 | 0.123 days |
Secondary
Median Serum PK Parameters at Month 0: CL
Serum PK parameters of clearance. 8 mg/kg was not reported for this outcome measure. Other arms were not provided due to participants meeting exclusion criteria: %AUCext \> 20% and R2 Adjusted \< 0.8. Affected parameters at participant visits meeting this criteria were excluded.
Time frame: Month 0
Population: Intensive pharmacokinetic population
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| VIS649 2 mg/kg | Median Serum PK Parameters at Month 0: CL | 257.89 mL/day | Standard Deviation 71.77 |
| VIS649 4 mg/kg | Median Serum PK Parameters at Month 0: CL | 315.94 mL/day | Standard Deviation 95.36 |
Secondary
Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16
Number of participants in each group achieving a greater than or equal to 30% decline from baseline in urinary protein/creatinine ratio (uPCR) at Months 9, 12, and 16
Time frame: Baseline to 9,12, and 16 months (16 months total)
Population: modified intent-to-treat (mITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS649 2 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 9 | 19 Participants |
| VIS649 2 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 16 | 18 Participants |
| VIS649 2 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 12 | 19 Participants |
| VIS649 4 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 9 | 20 Participants |
| VIS649 4 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 16 | 21 Participants |
| VIS649 4 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 12 | 24 Participants |
| VIS649 8 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 12 | 23 Participants |
| VIS649 8 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 9 | 21 Participants |
| VIS649 8 mg/kg | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 16 | 24 Participants |
| Placebo | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 9 | 7 Participants |
| Placebo | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 16 | 8 Participants |
| Placebo | Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16 | Month 12 | 11 Participants |
Secondary
Participants in Each Group Achieving Clinical Remission
Number of participants in each group achieving clinical remission. Clinical remission was defined as reduction in 24-hour urine protein excretion to less than 300 mg/day for at least 3 consecutive months.
Time frame: Baseline to End of Study (16 months)
Population: modified intent-to-treat (mITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIS649 2 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 9 | 4 Participants |
| VIS649 2 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 16 | 3 Participants |
| VIS649 2 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 12 | 3 Participants |
| VIS649 4 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 9 | 5 Participants |
| VIS649 4 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 16 | 7 Participants |
| VIS649 4 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 12 | 5 Participants |
| VIS649 8 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 12 | 10 Participants |
| VIS649 8 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 9 | 7 Participants |
| VIS649 8 mg/kg | Participants in Each Group Achieving Clinical Remission | Month 16 | 9 Participants |
| Placebo | Participants in Each Group Achieving Clinical Remission | Month 9 | 1 Participants |
| Placebo | Participants in Each Group Achieving Clinical Remission | Month 16 | 1 Participants |
| Placebo | Participants in Each Group Achieving Clinical Remission | Month 12 | 1 Participants |
Secondary
Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16
Percent change from baseline in total serum immunoglobin (Ig)A, IgG, and IgM concentrations at Months 12 and 16 in PD population
Time frame: Baseline to 12 and 16 months
Population: Pharmacodynamic Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VIS649 2 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 12 (Day 360) | 48.35 percentage change | Standard Deviation 12.431 |
| VIS649 2 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 16 (Day 485) | 79.49 percentage change | Standard Deviation 12.167 |
| VIS649 2 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 12 (Day 360) | 72.88 percentage change | Standard Deviation 9.816 |
| VIS649 2 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 16 (Day 485) | 97.20 percentage change | Standard Deviation 10.006 |
| VIS649 2 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 12 (Day 360) | 37.33 percentage change | Standard Deviation 13.279 |
| VIS649 2 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 16 (Day 485) | 85.67 percentage change | Standard Deviation 10.729 |
| VIS649 4 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 16 (Day 485) | 84.74 percentage change | Standard Deviation 20.481 |
| VIS649 4 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 16 (Day 485) | 96.00 percentage change | Standard Deviation 12.913 |
| VIS649 4 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 12 (Day 360) | 32.35 percentage change | Standard Deviation 10.403 |
| VIS649 4 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 12 (Day 360) | 66.91 percentage change | Standard Deviation 12.613 |
| VIS649 4 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 16 (Day 485) | 69.62 percentage change | Standard Deviation 14.79 |
| VIS649 4 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 12 (Day 360) | 30.55 percentage change | Standard Deviation 11.959 |
| VIS649 8 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 16 (Day 485) | 57.28 percentage change | Standard Deviation 14.645 |
| VIS649 8 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 12 (Day 360) | 65.40 percentage change | Standard Deviation 15.693 |
| VIS649 8 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 16 (Day 485) | 84.98 percentage change | Standard Deviation 20.144 |
| VIS649 8 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 16 (Day 485) | 62.51 percentage change | Standard Deviation 16.864 |
| VIS649 8 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 12 (Day 360) | 30.03 percentage change | Standard Deviation 8.017 |
| VIS649 8 mg/kg | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 12 (Day 360) | 31.07 percentage change | Standard Deviation 7.946 |
| Placebo | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 12 (Day 360) | 98.21 percentage change | Standard Deviation 13.656 |
| Placebo | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgM : Month 16 (Day 485) | 97.45 percentage change | Standard Deviation 13.239 |
| Placebo | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 16 (Day 485) | 101.22 percentage change | Standard Deviation 10.612 |
| Placebo | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 16 (Day 485) | 101.48 percentage change | Standard Deviation 12.84 |
| Placebo | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgA : Month 12 (Day 360) | 102.23 percentage change | Standard Deviation 10.584 |
| Placebo | Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16 | IgG : Month 12 (Day 360) | 68.31 percentage change | Standard Deviation 13.218 |