CSL312_3003 Safety and Pharmacokinetic Study in Subjects 2 to 11 Years of Age With Hereditary Angioedema

Phase 3CompletedNCT05819775

CSL Behring22 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hereditary Angioedema (HAE)

Interventions

CSL312BIOLOGICAL

Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously (SC)

Eligibility

Sex: ALLMin age: 2 YearsMax age: 11 Years

Medical Language ↔ Plain English

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.

Locations (13)

Research Solutions of Arizona

Litchfield Park, Arizona, United States

Medical Research of Arizona

Scottsdale, Arizona, United States

Donald S. Levy M.D.

Orange, California, United States

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAE)

Time frame: Up to Month 12

Percentage of Participants With TEAE

The percentage of participants was rounded to one place of decimal.

Time frame: Up to Month 12

Number of TEAE

Time frame: Up to Month 12

TEAE Rates Per Injection

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.

Time frame: Up to Month 12

TEAE Rates Per Participant-Year

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.

Time frame: Up to Month 12

Maximum Concentration (Cmax) of CSL312 at Steady-state

Time frame: Up to Month 12

Trough Concentration (Ctrough) of CSL312 at Steady-state

Time frame: At Months 3, 4, 6, 9, 10, and 12

Time to Maximum Concentration (Tmax) of CSL312 at Steady-State

Time frame: Up to Month 12

Secondary Outcomes

Data from ClinicalTrials.gov

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Raffi Tachdjian MD, Inc.

Santa Monica, California, United States

Bernstein Clinical Research

Cincinnati, Ohio, United States

PennState Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

AARA Research Center

Dallas, Texas, United States

Campbelltown Hospital, Western Sydney University

Campbelltown, Australia

Ottawa Allergy Research Corp

Ottawa, Canada

HZRM Hämophilie Zentrum Rhein Main GmbH

Frankfurt am Main, Hesse, Germany

...and 3 more locations

Time-normalized Number of HAE Attacks Per Month

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 frame: Up to Month 12

Time-normalized Number of HAE Attacks Per Year

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 frame: Up to Month 12

Time-normalized Number of HAE Attacks Treated With On-demand Treatment Per Month

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 frame: Up to Month 12

Time-normalized Number of HAE Attacks Treated With On-demand Treatment Per Year

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 frame: Up to Month 12

Time-normalized Number of Moderate and/or Severe HAE Attacks Per Month

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 frame: Up to Month 12

Time-normalized Number of Moderate and/or Severe HAE Attacks Per Year

Time frame: Up to Month 12

Percentage Reduction in the Time-normalized Number of HAE Attacks

The percentage reduction in the time-normalized number of HAE attacks was calculated within a participant as follows: 100\*\[ 1 - (Time-normalized number of HAE attacks per month during treatment period/Time-normalized number of HAE attacks per month from historical data)\].

Time frame: Up to Month 12

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

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.

Time frame: Up to Month 12

Number of Participants Experiencing Serious Adverse Events (SAE), Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation

Time frame: Up to Month 12

Percentage of Participants Experiencing SAE, Experiencing Death, Related TEAE, TEAE Leading to Study Discontinuation

The percentage of participants was rounded to one decimal place.

Time frame: Up to Month 12

Number of Participants With TEAE by Severity

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.

Time frame: Up to Month 12

Percentage of Participants With TEAE by Severity

Time frame: Up to Month 12

Number of Participants With Anti-CSL312 Antibodies

Time frame: At Day 1, Months 6 and 12

Percentage of Participants With Anti-CSL312 Antibodies

The percentage of participants was rounded to one place of decimal.

Time frame: At Day 1, Months 6 and 12

Number of Participants With Adverse Events of Special Interest (AESI)

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).

Time frame: Up to Month 12

Percentage of Participants With AESI

Time frame: Up to Month 12

FXIIa-mediated Kallikrein Activity

Time frame: 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

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.

Time frame: At Months 3, 4, and 12 and pre-dose and post dose at Months 6, 9, and 10

Number of Participants With Laboratory Findings Reported as AE

Time frame: Up to Month 12

Percentage of Participants With Laboratory Findings Reported as AE

The participant data were rounded to one decimal place.

Time frame: Up to Month 12