Hereditary Angioedema (HAE)
Conditions
Brief summary
The purpose of this study is to investigate the safety, PK / PD, and efficacy of SC CSL312 for prophylactic treatment of pediatric subjects with HAE.
Interventions
BIOLOGICALCSL312
Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously (SC)
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female 2. Aged 2 to 11 years, inclusive, with body weight ≥ 10th percentile based on age 3. Diagnosed with clinically confirmed C1-INH HAE 4. Experienced ≥ 2 HAE attacks during the 6 months before Screening
Exclusion criteria
1. Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema, recurrent angioedema associated with urticaria, or HAE type 3 2. Use of C1-INH products, androgens, antifibrinolytics, approved or future approved medications, or other small molecule medications for routine prophylaxis against HAE attacks within a minimum of 2 weeks before the Treatment Period 3. Participation in another interventional clinical study during the 30 days before the Treatment Period or within 5 half-lives of the final dose of the investigational product administered during the previous interventional study, whichever is longer 4. Having laboratory clinical abnormalities assessed as clinically significant by the investigator in results of hematology or chemistry assessments performed during Screening 5. Currently receiving a therapy not permitted during the study 6. Being pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | Up to Month 12 | — |
| Percentage of Participants With TEAE | Up to Month 12 | The percentage of participants was rounded to one place of decimal. |
| Number of TEAE | Up to Month 12 | — |
| TEAE Rates Per Injection | Up to Month 12 | The TEAE rate per injection was calculated as the number of TEAE/ number of injections. The number of injections was defined as the total injections a participant received during the Safety Evaluation Period under the dosing regimen to which the TEAE was assigned. |
| TEAE Rates Per Participant-Year | Up to Month 12 | The TEAE rate per participant year was calculated as number of TEAEs/ participant years. Participant-years of exposure were calculated as the sum of each participant's exposure duration (in years) under the specified dosing regimen or overall. For the time assigned to a dosing regimen, each study day was counted under the corresponding regimen. |
| Maximum Concentration (Cmax) of CSL312 at Steady-state | Up to Month 12 | — |
| Trough Concentration (Ctrough) of CSL312 at Steady-state | At Months 3, 4, 6, 9, 10, and 12 | — |
| Time to Maximum Concentration (Tmax) of CSL312 at Steady-State | Up to Month 12 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-normalized Number of HAE Attacks Per Month | Up to Month 12 | Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[Number of HAE attacks / Length of participant treatment in days\] \* 30.4375. |
| Time-normalized Number of HAE Attacks Per Year | Up to Month 12 | Time-normalized number of HAE attacks per year during treatment was calculated per participant as: \[Number of HAE attacks / Length of participant treatment in days\] \* 365.25. |
| Time-normalized Number of HAE Attacks Treated With On-demand Treatment Per Month | Up to Month 12 | The time-normalized number of HAE attacks per month treated with on-demand treatment were calculated as follows: \[(Number of HAE attacks treated with on - demand treatment during treatment period)/ Length of participant treatment in days\] ∗ 30.4375. |
| Time-normalized Number of HAE Attacks Treated With On-demand Treatment Per Year | Up to Month 12 | The time-normalized number of HAE attacks per year treated with on-demand treatment were calculated as follows: \[(Number of HAE attacks treated with on - demand treatment during treatment period)/ Length of participant treatment in days\] ∗ 365.25. |
| Time-normalized Number of Moderate and/or Severe HAE Attacks Per Month | Up to Month 12 | Time-normalized number of moderate or severe HAE attacks per month during treatment period was calculated per participant as: \[number of moderate or severe HAE attacks / length of participant treatment in days\] \* 30.4375. |
| Time-normalized Number of Moderate and/or Severe HAE Attacks Per Year | Up to Month 12 | Time-normalized number of moderate or severe HAE attacks per month during treatment period was calculated per participant as: \[number of moderate or severe HAE attacks / length of participant treatment in days\] \* 365.25. |
| Percentage Reduction in the Time-normalized Number of HAE Attacks | Up to Month 12 | The percentage reduction in the time-normalized number of HAE attacks was calculated within a participant as follows: 100\*\[ 1 - (Time-normalized number of HAE attacks per month during treatment period/Time-normalized number of HAE attacks per month from historical data)\]. |
| Number of Participants Experiencing at Least Greater Than or Equal to (>=) 50 Percent (%), >= 70%, >= 90%, or Equal to 100% (Attack-free) Reduction in the Time-normalized Number of HAE Attacks | Up to Month 12 | A participant was classified as a responder if the percentage reduction in the time-normalized number of HAE attacks under treatment compared to the time-normalized number of HAE attacks documented in the medical records was \>= 50%. Percent Reduction = 100 \* \[1 - (time-normalized number of HAE attacks during corresponding time window / time-normalized number of HAE attacks based on historical data)\]. Here number of participants experiencing at least \>= 50%, \>= 70%, \>= 90%, or equal to 100% (Attack-free) reduction in the time-normalized number of HAE attacks are reported. The number of responders at each reduction category have been reported. |
| Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation | Up to Month 12 | — |
| Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation | Up to Month 12 | The percentage of participants was rounded to one decimal place. |
| Number of Participants With TEAE by Severity | Up to Month 12 | Severity of AE was assessed by the investigator and categorized as mild, moderate and severe where: Mild: AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate: AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention. |
| Percentage of Participants With TEAE by Severity | Up to Month 12 | Severity of AE was assessed by the investigator and categorized as mild, moderate and severe where: Mild: AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate: AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention. The percentage of participants was rounded to one place of decimal. |
| Number of Participants With Anti-CSL312 Antibodies | At Day 1, Months 6 and 12 | — |
| Percentage of Participants With Anti-CSL312 Antibodies | At Day 1, Months 6 and 12 | The percentage of participants was rounded to one place of decimal. |
| Number of Participants With Adverse Events of Special Interest (AESI) | Up to Month 12 | AESI included severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators and suggestive events were independently identified for further review with a Standardized MedDRA Query (SMQ). |
| Percentage of Participants With AESI | Up to Month 12 | AESI included severe hypersensitivity including anaphylaxis. The AESI reported have been identified by investigators and suggestive events were independently identified for further review with an SMQ. The percentage of participants was rounded to one place of decimal. |
| FXIIa-mediated Kallikrein Activity | At Months 3, 4, and 12 and pre-dose and post dose at Months 6, 9, and 10 | — |
| Percent of Baseline FXIIa-mediated Kallikrein Activity | At Months 3, 4, and 12 and pre-dose and post dose at Months 6, 9, and 10 | Percent of Baseline at Visit \[i\] = 100 \* (actual value at Visit \[i\] / Baseline value), where Baseline is defined as the most recent, non-missing value before the first IP administration (including unscheduled visits). Here unit of measure is Percent (%) of FXIIa-mediated Kallikrein Activity. |
| Number of Participants With Laboratory Findings Reported as AE | Up to Month 12 | — |
| Percentage of Participants With Laboratory Findings Reported as AE | Up to Month 12 | The participant data were rounded to one decimal place. |
Countries
Australia, Canada, Germany, Israel, United States
Contacts
STUDY_DIRECTORStudy Director
CSL Behring
Participant flow
Recruitment details
This study was conducted at 9 sites in the United States, Australia, Canada, Germany, and Israel.
Pre-assignment details
A total of 24 participants were screened, of whom 22 were enrolled and 2 were screen failures.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 22 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 3.7 Years STANDARD_DEVIATION 1.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 21 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 16 |
| other Total, other adverse events | 5 / 6 | 11 / 16 |
| serious Total, serious adverse events | 0 / 6 | 1 / 16 |
Outcome results
None listed