Primary Sjögren's Syndrome
Conditions
Brief summary
A Phase 2a study to evaluate the efficacy and safety of AMG 557/MEDI5872 in Primary Sjögren's Syndrome
Detailed description
This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the clinical and biologic efficacy, as well as the safety of SC doses of AMG 557/MEDI5872 in adult subjects with Primary Sjögren's Syndrome.
Interventions
BIOLOGICALAMG 557/MEDI5872
Participants will receive a fixed SC dose of 210 mg MEDI5872 (AMG 557/MEDI5872) QW for 3 weeks (Days 1 to 15) and then Q2W for 9 weeks (Days 29 to 85) in double-blind period of the study. In open-label period, all participants from double-blind period will receive a fixed SC dose of 210 mg MEDI5872 from Day 99 to Day 183 (QW from Days 99 to 113 for participants from Placebo arm and on Days 99 and 113 for participants from MEDI5872 210 mg arm; and Q2W from Days 127 to 183 for participants from both arms).
OTHERPlacebo
The SC dose of placebo every week for 3 weeks (Days 1 to 15) and then every 2 weeks for 9 weeks (Days 29 to 85) in double-blind period of the study. In open-label period, an additional dose of blinded placebo will be administered on Day 106 for participants who will receive MEDI5872 210mg in double-blinded period.
Sponsors
Amgen
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 through 75 years at the time of signing the ICF. * Fulfill American-European Consensus Group (AECG) criteria for pSS * ESSDAI score ≥ 6. * Positive anti-SS-A and/or anti-SS-B autoantibodies and at least IgG \> 13 g/L or RF level \> upper limit of normal (ULN) or positive test for cryoglobulins * Willingness to undergo protocol-required minor salivary gland biopsies. * Negative TB test during screening * Immunization up to date as determined by local standard of care.
Exclusion criteria
* Previous treatment with AMG 557/MEDI5872. * Evidence of signs or symptoms of a viral, bacterial, or fungal infection within 2 weeks (14 days) prior to randomization (Day 1) according to the assessment of the investigator; any infection requiring IV antibiotic or antiviral treatment within 8 weeks of randomization (Day 1); history of herpes zoster within 3 months prior to randomization (Day 1). * Evidence of significant renal insufficiency * Positive test at screening for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) antibody. * Prior administration of any of the following: 1. Belimumab in the past 6 months prior to randomization (Day 1); 2. Rituximab in the past 12 months or CD19+ B cells \< 5/µL if rituximab treatment was more than 12 months prior to randomization (Day 1); 3. Abatacept in the past 6 months prior to randomization (Day 1); 4. Tumor necrosis factor inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) in the past 3 months prior to randomization (Day 1); 5. Tocilizumab in the past 3 months prior to randomization (Day 1); 6. Cyclophosphamide (or any other alkylating agent) in the past 6 months prior to randomization (Day 1); cyclosporine (except for eye drops), tacrolimus, sirolimus, mycophenolate mofetil, azathioprine, or leflunomide in the past 3 months prior to randomization (Day 1). * Receiving any of the following: 1. Corticosteroids: \> 10 mg/day oral prednisone (or equivalent); Any change or initiation of new dose within 4 weeks prior to signing the ICF through randomization (Day 1); Intramuscular, IV, or intra-articular corticosteroids within 4 weeks prior to signing the ICF through randomization (Day 1); Any change or initiation of new dose of topical corticosteroids within 2 weeks prior to signing the ICF through randomization (Day 1); 2. Antimalarials: any increase or initiation of new dose of antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) within 12 weeks prior to signing the ICF through randomization (Day 1). 3. Methotrexate: \> 20 mg/week methotrexate; Any change or initiation of new dose of methotrexate within 4 weeks prior to signing the ICF through randomization (Day 1); Any change in route of administration. 4. Any increase or initiation of new dose of regularly scheduled nonsteroidal anti inflammatory drugs (NSAIDs) within 2 weeks prior to signing the ICF through randomization (Day 1). 5. Cevimeline or pilocarpine and cyclosporine eye drops (Restasis): any increase or initiation of new doses within 2 weeks prior to signing the ICF through randomization (Day 1).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99 | Baseline (Day 1 predose) and Day 99 | The European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (i.e., no, low, moderate, high) according to their severity (no disease activity equals to 0 and for high disease activity the domain score equals 3 or 4). Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease. Adjusted mean change and standard error are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 | Baseline (Day 1 predose) and Day 99 | The minor salivary gland biopsy biomarkers included total plasma cell levels, CD4/ inducible T-cell costimulator (ICOS) TFH cells, and PD-1/ICOS TFH cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented. |
| Ratio to Baseline in Focus Score at Day 99 | Baseline (Day 1 predose) and Day 99 | The focus score is a semi-quantitative assessment of focal lymphocytic sialoadenitis, which is defined as the presence of \>= 1 dense aggregate of 50 or more lymphocytes in a 4 mm2 area. Higher numbers are associated with more inflammation. |
| Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99 | Baseline (Day 1 predose) and Day 99 | The European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) is a patient-reported, subjective symptom index for primary Sjögren's syndrome. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Adjusted mean change and standard error are presented. |
| Ratio to Baseline in Peripheral Blood Biomarkers at Day 99 | Baseline (Day 1 predose) and Day 99 | The peripheral blood biomarkers included total plasma cell levels (including plasma blast levels) and T follicular helper (TFH) cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were collected from Day 1 (postdose) until Day 99 for 'Placebo' arm and Day 296 for 'Any MEDI5872 210 mg' arm that were absent before treatment or that worsened relative to pre-treatment state. |
| Number of Participants With Adverse Events of Special Interest (AESIs) | Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period | An AESI (serious or non-serious) was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, new or reactivated tuberculosis infection, malignancy, and hypersensitivity and anaphylactic reactions. Treatment-emergent AESIs were collected from Day 1 (postdose) until Day 99 for 'Placebo' arm and Day 296 for 'Any MEDI5872 210 mg' arm. |
| Percentage of ESSDAI Responders at Day 99 | Baseline (Day 1 predose) and Day 99 | The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (no, low, moderate, high) according to their severity (0=no disease activity and ¾ = high disease activity of the domain). Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 \[best\] to 123 \[worst activity\]). Participants are considered to be an ESSDAI\[x\] responder as they achieved a reduction of x points or more in ESSDAI score, did not prematurely discontinue the study drug, and did not receive prohibited concomitant medications. |
Countries
France, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted across 4 countries (France, United Kingdom, Sweden, and the United States).
Pre-assignment details
A total of 59 participants were screened in the study. Of which, 27 participants were screen failures and 32 participants were randomized and enrolled in study. The results are posted per the data of primary efficacy analysis last participant last visit date.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/MEDI5872 210 mg Participants received a subcutaneous (SC) dose of placebo matching with MEDI5872 every week (QW) for 3 weeks (Days 1, 8, and 15) and then every 2 weeks (Q2W) for next 9 weeks (Days 29 to 85) in double-blind period of the study. In open-label period, participants received MEDI5872 QW from Days 99 to 113 and Q2W from Days 127 to 183. | 16 |
| MEDI5872 210 mg/MEDI5872 210 mg Participants received a fixed SC dose of 210 mg MEDI5872 every week (QW) for 3 weeks (Days 1 to 15) and then every 2 weeks (Q2W) for next 9 weeks (Days 29 to 85) in double-blind period of the study. In open-label period, participants continued dosing of MEDI5872 210mg Q2W from Days 99 to 183 and received an additional dose of blinded placebo on Day 106. | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period | Adverse Event | 0 | 1 |
| Double-blind Period | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | MEDI5872 210 mg/MEDI5872 210 mg | Total | Placebo/MEDI5872 210 mg |
|---|---|---|---|
| Age, Continuous | 51.1 Years STANDARD_DEVIATION 14.3 | 50.7 Years STANDARD_DEVIATION 13 | 50.2 Years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 28 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 27 Participants | 14 Participants |
| Sex: Female, Male Female | 14 Participants | 28 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 31 |
| other Total, other adverse events | 14 / 16 | 29 / 31 |
| serious Total, serious adverse events | 0 / 16 | 1 / 31 |
Outcome results
Primary
Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99
The European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (i.e., no, low, moderate, high) according to their severity (no disease activity equals to 0 and for high disease activity the domain score equals 3 or 4). Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease. Adjusted mean change and standard error are presented.
Time frame: Baseline (Day 1 predose) and Day 99
Population: Intent-to-treat (ITT) population included all randomized and treated participants, grouped according to assigned treatment. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99 | -2.3 Scores on a scale | Standard Error 0.8 |
| MEDI5872 210 mg | Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99 | -3.8 Scores on a scale | Standard Error 0.9 |
p-value: 0.26290% CI: [-3.6, 0.7]ANCOVA
Secondary
Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99
The European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) is a patient-reported, subjective symptom index for primary Sjögren's syndrome. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Adjusted mean change and standard error are presented.
Time frame: Baseline (Day 1 predose) and Day 99
Population: The ITT population included all randomized and treated participants, grouped according to assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99 | -1.0 Scores on a scale | Standard Error 0.5 |
| MEDI5872 210 mg | Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI) Score at Day 99 | -0.6 Scores on a scale | Standard Error 0.5 |
p-value: 0.57490% CI: [-0.8, 1.6]ANCOVA
Secondary
Number of Participants With Adverse Events of Special Interest (AESIs)
An AESI (serious or non-serious) was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, new or reactivated tuberculosis infection, malignancy, and hypersensitivity and anaphylactic reactions. Treatment-emergent AESIs were collected from Day 1 (postdose) until Day 99 for 'Placebo' arm and Day 296 for 'Any MEDI5872 210 mg' arm.
Time frame: Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period
Population: Placebo: As-treated population (participants grouped per actual treatment received).~Any MEDI5872 210 mg: Any MEDI5872 population (participants received at least 1 dose of MEDI5872 either in double-blind and/or open-label). 1 participant from 'Placebo' discontinued treatment before Day 99 and didn't receive MEDI5872 dose in open-label period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events of Special Interest (AESIs) | 1 Participants |
| MEDI5872 210 mg | Number of Participants With Adverse Events of Special Interest (AESIs) | 6 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were collected from Day 1 (postdose) until Day 99 for 'Placebo' arm and Day 296 for 'Any MEDI5872 210 mg' arm that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period
Population: Placebo: As-treated population (participants grouped per actual treatment received).~Any MEDI5872 210 mg: Any MEDI5872 population (participants received at least 1 dose of MEDI5872 either in double-blind and/or open-label). 1 participant from 'Placebo' discontinued treatment before Day 99 and didn't receive MEDI5872 dose in open-label period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 14 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 0 Participants |
| MEDI5872 210 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 29 Participants |
| MEDI5872 210 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 1 Participants |
Secondary
Percentage of ESSDAI Responders at Day 99
The ESSDAI is a clinical index that measures Sjogren's syndrome disease activity. A physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological). Each domain is assessed for activity level in 3 or 4 levels (no, low, moderate, high) according to their severity (0=no disease activity and ¾ = high disease activity of the domain). Each domain is assigned a weight between 1 and 6, and the domain score is multiplied by the domain weight. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 \[best\] to 123 \[worst activity\]). Participants are considered to be an ESSDAI\[x\] responder as they achieved a reduction of x points or more in ESSDAI score, did not prematurely discontinue the study drug, and did not receive prohibited concomitant medications.
Time frame: Baseline (Day 1 predose) and Day 99
Population: The ITT population included all randomized and treated participants, grouped according to assigned treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of ESSDAI Responders at Day 99 | ESSDAI [3] | 18.8 Percentage of participants |
| Placebo | Percentage of ESSDAI Responders at Day 99 | ESSDAI [4] | 18.8 Percentage of participants |
| MEDI5872 210 mg | Percentage of ESSDAI Responders at Day 99 | ESSDAI [3] | 43.8 Percentage of participants |
| MEDI5872 210 mg | Percentage of ESSDAI Responders at Day 99 | ESSDAI [4] | 43.8 Percentage of participants |
Comparison: ESSDAI \[3\]p-value: 0.25290% CI: [-3.1, 50.9]Fisher Exact
Comparison: ESSDAI\[4\]p-value: 0.25290% CI: [-3.1, 50.9]Fisher Exact
Secondary
Ratio to Baseline in Focus Score at Day 99
The focus score is a semi-quantitative assessment of focal lymphocytic sialoadenitis, which is defined as the presence of \>= 1 dense aggregate of 50 or more lymphocytes in a 4 mm2 area. Higher numbers are associated with more inflammation.
Time frame: Baseline (Day 1 predose) and Day 99
Population: The ITT population included all randomized and treated participants, grouped according to assigned treatment. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ratio to Baseline in Focus Score at Day 99 | 0.79 Ratio | Standard Deviation 0.53 |
| MEDI5872 210 mg | Ratio to Baseline in Focus Score at Day 99 | 0.96 Ratio | Standard Deviation 0.5 |
Secondary
Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99
The minor salivary gland biopsy biomarkers included total plasma cell levels, CD4/ inducible T-cell costimulator (ICOS) TFH cells, and PD-1/ICOS TFH cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented.
Time frame: Baseline (Day 1 predose) and Day 99
Population: The ITT population included all randomized and treated participants, grouped according to assigned treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 | Total Plasma Cells | 1.32 Ratio | Standard Error 0.13 |
| Placebo | Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 | CD4/ICOS TFH Cells | 1.76 Ratio | Standard Error 0.21 |
| Placebo | Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 | PD-1/ICOS TFH Cells | 1.06 Ratio | Standard Error 0.19 |
| MEDI5872 210 mg | Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 | Total Plasma Cells | 1.15 Ratio | Standard Error 0.11 |
| MEDI5872 210 mg | Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 | CD4/ICOS TFH Cells | 0.75 Ratio | Standard Error 0.18 |
| MEDI5872 210 mg | Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99 | PD-1/ICOS TFH Cells | 1.07 Ratio | Standard Error 0.16 |
Comparison: For total plasma cellsp-value: 0.4490% CI: [0.65, 1.18]ANCOVA
Comparison: For CD4/ICOS TFH cellsp-value: 0.00890% CI: [0.26, 0.7]ANCOVA
Comparison: For PD-1/ICOS TFH cellsp-value: 0.97290% CI: [0.64, 1.59]ANCOVA
Secondary
Ratio to Baseline in Peripheral Blood Biomarkers at Day 99
The peripheral blood biomarkers included total plasma cell levels (including plasma blast levels) and T follicular helper (TFH) cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented.
Time frame: Baseline (Day 1 predose) and Day 99
Population: The ITT population included all randomized and treated participants, grouped according to assigned treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Ratio to Baseline in Peripheral Blood Biomarkers at Day 99 | Plasma Cell Levels | 0.70 Ratio | Standard Error 0.24 |
| Placebo | Ratio to Baseline in Peripheral Blood Biomarkers at Day 99 | TFH Cells | 0.94 Ratio | Standard Error 0.27 |
| MEDI5872 210 mg | Ratio to Baseline in Peripheral Blood Biomarkers at Day 99 | Plasma Cell Levels | 0.65 Ratio | Standard Error 0.24 |
| MEDI5872 210 mg | Ratio to Baseline in Peripheral Blood Biomarkers at Day 99 | TFH Cells | 0.62 Ratio | Standard Error 0.27 |
Comparison: For plasma cell levelsp-value: 0.8290% CI: [0.52, 1.64]ANCOVA
Comparison: For TFH cellsp-value: 0.29190% CI: [0.33, 1.28]ANCOVA