IgG4-RD
Conditions
Brief summary
The purpose of this Phase 2 study is to investigate the effect of XmAb5871 on IgG4-Related Disease (RD) activity
Interventions
BIOLOGICALXmAb5871
Sponsors
Massachusetts General Hospital
Xencor, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Active IgG4-RD * Compatible pattern of organ involvement consistent with IgG4-RD that cannot be attributed to other causes * Histopathologically-proven diagnosis of IgG4-RD * Peripheral blood plasmablast count \>900 cells/mL and/or elevated IgG4-RD levels during screening * Able and willing to complete the entire study according to the study schedule * Able and willing to provide written informed consent
Exclusion criteria
* History or evidence of a clinically unstable/uncontrolled disorder, condition or disease other than IgG4-RD that, in the opinion of the Investigator would pose a risk to the patient safety or interfere with the study evaluation, procedures or completion * Malignancy within 5 years (except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin, or prostate cancer with no recurrence ≥3 years following prostatectomy) * Presence of recurrent or chronic infections, defined as ≥3 infections requiring antimicrobials over the past 6 months prior to screening * Active infection requiring hospitalization or treatment with parenteral antimicrobials within the 60 days prior to randomization or oral antimicrobials within the 21 days prior to enrollment * Patient is taking \>40 mg of prednisone QD * Prior use of rituximab (or other B cell depleting agents) within 6 months of enrollment. Prior use of any B cell depleting agent greater than 6 months from enrollment is allowed if the CD19+ B cell count is within the normal reference range during screening * Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-life is unknown) prior to enrollment * Immunosuppressive agent use within the three months prior to enrollment * Has received live vaccines within 2 months of enrollment * Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to end-of-study visit * Unable or unwilling to partake in the follow-up assessments or required protocol procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With an Improvement in IgG4-RD Activity | Baseline Day 1 to Day 169 | Improvement of disease activity as defined by a decrease of IgG4-RD responder index \>= 2 points from Day 1 pre-dose disease activity score. The IgG4-RD Responder Index Total Activity Score ranges from 0 to a maximum of 162. Higher scores represent greater (i.e. worse) disease activity. A score of 0 represents no disease activity other than residual fibrosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing a Treatment-emergent Adverse Event as Assessed by CTCAE v4.3 | Baseline Day 1 to Day 197 | The number of patients experiencing a treatment-emergent adverse event as assessed by CTCAE v4.3 will be tabulated according to MedDRA system-organ class and preferred term, intensity and causality. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| XmAb5871 5 mg/kg 5 mg/kg weight-based dosing group | 15 |
| XmAb5871 Fixed Dose 90 mg or 180 mg fixed dose group | 5 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
Baseline characteristics
| Characteristic | XmAb5871 5 mg/kg | Total | XmAb5871 Fixed Dose |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 10.57 | 57.9 years STANDARD_DEVIATION 11.82 | 51.2 years STANDARD_DEVIATION 14.11 |
| Baseline IgG4-RD Responder Index Total Activity Score | 11.5 Total Activity Score STANDARD_DEVIATION 6.65 | 11.8 Total Activity Score STANDARD_DEVIATION 6.45 | 12.8 Total Activity Score STANDARD_DEVIATION 6.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 20 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Involved Areas at Baseline Bile Ducts | 2 Participants | 2 Participants | 0 Participants |
| Involved Areas at Baseline Constitutional Symptoms | 6 Participants | 7 Participants | 1 Participants |
| Involved Areas at Baseline Heart / Pericardium | 3 Participants | 3 Participants | 0 Participants |
| Involved Areas at Baseline Kidney | 5 Participants | 6 Participants | 1 Participants |
| Involved Areas at Baseline Lacrimal Glands | 7 Participants | 10 Participants | 3 Participants |
| Involved Areas at Baseline Lungs | 4 Participants | 6 Participants | 2 Participants |
| Involved Areas at Baseline Lymph Nodes | 10 Participants | 14 Participants | 4 Participants |
| Involved Areas at Baseline Nasal Cavity Lesion | 3 Participants | 3 Participants | 0 Participants |
| Involved Areas at Baseline Orbital Lesion | 2 Participants | 3 Participants | 1 Participants |
| Involved Areas at Baseline Other | 4 Participants | 8 Participants | 4 Participants |
| Involved Areas at Baseline Other ENT Lesions, e.g. tonsillitis, pharyngitis | 2 Participants | 2 Participants | 0 Participants |
| Involved Areas at Baseline Other Salivary Glands | 1 Participants | 1 Participants | 0 Participants |
| Involved Areas at Baseline Pancreas | 1 Participants | 4 Participants | 3 Participants |
| Involved Areas at Baseline Parotid Glands | 8 Participants | 10 Participants | 2 Participants |
| Involved Areas at Baseline Retroperitoneal Fibrosis | 1 Participants | 2 Participants | 1 Participants |
| Involved Areas at Baseline Sinusitis | 2 Participants | 4 Participants | 2 Participants |
| Involved Areas at Baseline Skin | 0 Participants | 1 Participants | 1 Participants |
| Involved Areas at Baseline Submandibular Glands | 9 Participants | 12 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 15 Participants | 3 Participants |
| Region of Enrollment United States | 15 Participants | 20 Participants | 5 Participants |
| Serum IgG4 level at Baseline | 440.33 mg/dL STANDARD_DEVIATION 622.99 | 544.90 mg/dL STANDARD_DEVIATION 588.674 | 858.60 mg/dL STANDARD_DEVIATION 351.608 |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 1 Participants |
| Sex: Female, Male Male | 10 Participants | 14 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 5 |
| other Total, other adverse events | 7 / 15 | 3 / 5 |
| serious Total, serious adverse events | 1 / 15 | 1 / 5 |
Outcome results
Primary
Proportion of Patients With an Improvement in IgG4-RD Activity
Improvement of disease activity as defined by a decrease of IgG4-RD responder index \>= 2 points from Day 1 pre-dose disease activity score. The IgG4-RD Responder Index Total Activity Score ranges from 0 to a maximum of 162. Higher scores represent greater (i.e. worse) disease activity. A score of 0 represents no disease activity other than residual fibrosis.
Time frame: Baseline Day 1 to Day 169
Population: Intent to Treat (ITT) Population: All patients who have received at least a partial dose of XmAb5871.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| XmAb5871 5 mg/kg | Proportion of Patients With an Improvement in IgG4-RD Activity | Responder at Day 169 visit | 12 Participants |
| XmAb5871 5 mg/kg | Proportion of Patients With an Improvement in IgG4-RD Activity | Non-Responder at Day 169 visit | 2 Participants |
| XmAb5871 5 mg/kg | Proportion of Patients With an Improvement in IgG4-RD Activity | Not Assessed at Day 169 visit | 1 Participants |
| XmAb5871 Fixed Dose | Proportion of Patients With an Improvement in IgG4-RD Activity | Responder at Day 169 visit | 4 Participants |
| XmAb5871 Fixed Dose | Proportion of Patients With an Improvement in IgG4-RD Activity | Non-Responder at Day 169 visit | 0 Participants |
| XmAb5871 Fixed Dose | Proportion of Patients With an Improvement in IgG4-RD Activity | Not Assessed at Day 169 visit | 1 Participants |
Secondary
Number of Patients Experiencing a Treatment-emergent Adverse Event as Assessed by CTCAE v4.3
The number of patients experiencing a treatment-emergent adverse event as assessed by CTCAE v4.3 will be tabulated according to MedDRA system-organ class and preferred term, intensity and causality.
Time frame: Baseline Day 1 to Day 197
Population: Safety Population: All patients who receive at least a partial dose of XmAb5871.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XmAb5871 5 mg/kg | Number of Patients Experiencing a Treatment-emergent Adverse Event as Assessed by CTCAE v4.3 | 13 Participants |
| XmAb5871 Fixed Dose | Number of Patients Experiencing a Treatment-emergent Adverse Event as Assessed by CTCAE v4.3 | 5 Participants |