Warm Autoimmune Hemolytic Anemia (wAIHA)
Conditions
Keywords
AIHA, C1q, complement, RBC lysis
Brief summary
This study will evaluate the safety and tolerability of ANX005 in participants with Warm Autoimmune Hemolytic Anemia (wAIHA).
Detailed description
After being informed of study details and potential risks, all participants who provide written informed consent will undergo an up to 6-week screening period to determine eligibility. Participants who meet the eligibility criteria will receive two once-weekly intravenous (IV) infusions of ANX005. Participants will return to the clinic weekly through Week 10 for study assessments. The total duration of individual participation in this study will be up to 16 weeks.
Interventions
DRUGANX005
ANX005 is provided as a solution for IV infusion
Sponsors
Annexon, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or non-pregnant, non-lactating female ≥18 years of age (no maximum age). * Diagnosis of wAIHA at least 3 months prior to screening with a direct antiglobulin test (DAT) ≥1 positive for immunoglobulin G (IgG)±C3, or a diagnosis of mixed autoimmune hemolytic anemia (AIHA) that is DAT positive for both IgG and C3, with a presence of a cold antibody with a thermal amplitude ≥30ºCelcius. * Hemoglobin (Hgb) level ≤10.0 grams/deciliter (pre-transfusion). * Evidence of classical complement pathway activation. * Evidence of active hemolysis. * Stable use of glucocorticoids and immunosuppressants are permitted. * Vaccinations against encapsulated bacterial organisms within 5 years prior to screening or participant must be willing to receive prophylaxis against infections with encapsulated bacteria via vaccination and/or the use of prophylactic antibiotics in accordance with local standards of practice and/or guidelines.
Exclusion criteria
* Elevated aspartate aminotransferase or alanine aminotransferase levels \>2.5 times the upper limit of normal. * Platelet count \<30 X 10\^9/liter. * History of cold agglutinin disease. * History of solid organ, bone marrow, or stem cell transplantation. * History of splenectomy within the 3 months prior to screening. * Received rituximab or other anti-CD20 monoclonal antibody \<3 months prior to screening. * Intravenous immunoglobulin (IVIg) treatment within 3 months prior to screening or plasmapheresis or immunoadsorption treatment within 60 days prior to screening. * Clinically significant, recent, or ongoing illness or medical condition, including coexistent autoimmune disorder, malignancy, HIV, hepatitis B virus, and hepatitis C virus. * History of meningitis or septicemia within the past 2 years. * Treatment with an investigational therapeutic agent within 30 days prior to screening. * Hypersensitivity to any drug product or excipients used in this study or to previous IV medication administration. * Body weight less than 50 kilograms (kg) or greater than 100 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Day 1 through Day 71 | An adverse event (AE) was any untoward medical occurrence in a participant who had been administered a pharmaceutical product. An AE did not necessarily have a causal relationship with the product and therefore could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product. An AE could arise with any use, route of administration, formulation, dose (including an overdose), or when used in combination with another pharmaceutical product. A TEAE was an AE with an onset date/time after the first infusion of ANX005 until the end of the study. A summary of serious and all other non-serious adverse events regardless of causality is located in the Adverse Events module. |
| Maximum Change From Baseline in Hemoglobin Levels | Baseline up to Day 71 | Maximum change from Baseline was calculated as the maximum post-Baseline value observed up to Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
| Change From Baseline in Lactate Dehydrogenase Levels at Day 71 | Baseline, Day 71 | Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
| Change From Baseline in Percentage of Reticulocytes/Total Cells Count at Day 71 | Baseline, Day 71 | Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
| Change From Baseline in Haptoglobin Levels at Day 71 | Baseline, Day 71 | Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
| Change From Baseline in Total Bilirubin Levels at Day 71 | Baseline, Day 71 | Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
| Change From Baseline in Indirect Bilirubin Levels at Day 71 | Baseline, Day 71 | Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Inhibition Complement CH50 From Baseline Through Day 71 | Baseline, Days 2, 4, 8, 15, 22, 29, 36, 43, 50, 57, and 71 | Change in percent inhibition complement CH50 from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. A decrease form baseline indicated a better outcome. |
| Change From Baseline in Complement C4 Level Through Day 71 | Baseline, Days 2, 4, 8 (pre-dose and end of infusion), 15, 22, 29, 36, 43, 50, 57, and 71 | Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
| Change From Baseline in Complement C1q Level Through Day 71 | Baseline, Days 2 (4 hours [hr] after Infusion and end of infusion), 4, 8 (pre-dose, 4 hr after Infusion, and end of infusion), 15, 22, 29, 36, 43, 50, 57, and 71 | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005. |
Countries
Australia, Austria, Bulgaria, United States
Contacts
STUDY_DIRECTORStudy Director
Annexon, Inc.
Participant flow
Pre-assignment details
Participants with wAIHA who met eligibility criteria were enrolled.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 7.56 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 5 Participants |
| Age, Customized Children (2-11 years) | 0 Participants |
| Age, Customized From 65-84 years | 1 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
None listed