C1 ESTERASE INHIBITOR (HUMAN) for Hereditary angioedema | Hereditary angioedema type I | Hereditary angioedema type II | Acute hereditary angioedema attack

Inclusion criteria

• {"criterion_text":"- Is at least 18 years of age (applicable for 1st study phase) or is at least 2 years of age (applicable for 2nd study phase)"}
• {"criterion_text":"- Has confirmed diagnosis of HAE type I or II"}
• {"criterion_text":"- Has had at least 3 moderate or severe HAE attacks (excluding extremity attacks) in the last 3 months before the Screening Visit. For participants ≥2 and ≤12 years of age, has had at least 1 moderate or severe HAE attack (excluding extremity attacks) in the last 6 months before Screening Visit"}
• {"criterion_text":"- Has a documented congenital C1-INH functional activity <50% with or without C1-INH deficiency and C4 antigen level below the laboratory reference range"}
• {"criterion_text":"- Participant or the participant’s legally authorized representative(s) has signed informed consent (as required by local law), with the assent of participants legally capable of providing it, as applicable"}
• {"criterion_text":"- States willingness to comply with all study procedures and availability for the duration of the study"}
• {"criterion_text":"- If the participant is of childbearing potential (CBP), has a negative pregnancy test and must have been using a highly effective method of contraception and continue to do so until at least 2 weeks after their last dose (for both blinded and open-label doses of IMP). Not of CBP is defined as surgically sterilized (hysterectomy, bilateral oophorectomy) or who are postmenopausal (defined as women with no menses for 12 months without an alternative medical cause)"}

Exclusion criteria

• {"criterion_text":"- Has a history of clinically relevant antibody development against C1-INH"}
• {"criterion_text":"- (applicable until IDMC review of the interim preliminary safety and efficacy data): has clinically significant derangement in measurements of cardiovascular status (i.e. uncontrolled arterial hypertension, cardiac insufficiency New York Heart Association (NYHA) class III-IV), pulmonary status (i.e., COPD GOLD classification 3 and 4, severe asthma) and renal status (i.e., eGFR below 90 ml/min per 1.73 m2)"}
• {"criterion_text":"- Has a medical history consistent with Type 3 HAE (i.e., onset at age above 40 year, no family history, no known HAE mutation, low C1q level in plasma)"}
• {"criterion_text":"- Has a history of allergic reaction to C1-INH or other blood/plasma product"}
• {"criterion_text":"- Has a history of B-cell malignancy that was unresolved in the past 5 years"}
• {"criterion_text":"- Has a narcotic and/or alcoholic addiction"}
• {"criterion_text":"- Has participated in any other investigational drug evaluation within 30 days before screening"}
• {"criterion_text":"- Is pregnant or breastfeeding"}
• {"criterion_text":"- Has any clinically significant medical or psychiatric condition that, in the investigator’s opinion would interfere with the participant’s ability to participate in the study"}
• {"criterion_text":"- Has a history of thromboembolic events (TEEs), myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebrovascular accident, transient ischemic attack, severe peripheral vascular disease, or disseminated intravascular coagulation within one year before screening"}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint of this study is the time to the beginning of unequivocal symptom relief at the defining attack site (site of swelling or pain) in blinded participants. Participants will rate symptom relief for the defining site from the start of the IMP injection every 15 minutes over 4 hours.","definition_or_measurement_approach":"Participants will rate symptom relief for the defining site from the start of the IMP injection every 15 minutes over 4 hours; endpoint is time to beginning of unequivocal symptom relief at the defining attack site."}

Secondary endpoints

• {"endpoint_text":"- Percentage of participants responding to treatment, defined as beginning of unequivocal symptom relief at the defining site within 4 hours after injection (once per participant after first QAT in the study)","definition_or_measurement_approach":"Response defined as beginning of unequivocal symptom relief at the defining site within 4 hours after injection; measured once per participant after first QAT in the study."}
• {"endpoint_text":"- Time to the beginning of unequivocal symptom relief at all sites involved within 4 hours after injection","definition_or_measurement_approach":"Time from injection to beginning of unequivocal symptom relief at all sites involved, assessed within 4 hours after injection."}
• {"endpoint_text":"- Changes in symptom severity at the defining site by visual analog scale (VAS) rating from pre-injection over 4 hours after injection","definition_or_measurement_approach":"Change in VAS rating from pre-injection to assessments over 4 hours post-injection."}
• {"endpoint_text":"- Time to the beginning of unequivocal symptom relief at the defining site in participants receiving open-label treatment within 4 hours after injection","definition_or_measurement_approach":"Time from open-label injection to beginning of unequivocal symptom relief at defining site within 4 hours."}
• {"endpoint_text":"- Percentage of participants responding to treatment, defined as beginning of unequivocal symptom relief at the defining site within 4 hours after injection","definition_or_measurement_approach":"Percentage of participants with symptom relief at defining site within 4 hours after injection."}
• {"endpoint_text":"- Changes in symptom severity at the defining site by VAS rating from pre-injection over 4 hours after injection","definition_or_measurement_approach":"Change in VAS rating from pre-injection to 4 hours post-injection."}
• {"endpoint_text":"- Time to the beginning of unequivocal symptom relief at all sites involved within 4 hours after injection","definition_or_measurement_approach":"Time to symptom relief at all involved sites within 4 hours after injection."}
• {"endpoint_text":"- Time from each open-label injection start to complete resolution of QAT attacks","definition_or_measurement_approach":"Time from start of each open-label injection to complete resolution of QAT attacks."}
• {"endpoint_text":"- Percentage of repeated attacks per participant with unequivocal symptom relief at the defining site beginning within 4 hours after injection for subsequent attacks","definition_or_measurement_approach":"Percentage of repeated attacks per participant where symptom relief at defining site begins within 4 hours for subsequent attacks."}
• {"endpoint_text":"- Time from each open-label injection start to beginning of unequivocal symptom relief at the defining site for subsequent attacks within 4 hours after injection","definition_or_measurement_approach":"Time from each open-label injection to beginning of symptom relief at defining site for subsequent attacks, within 4 hours."}
• {"endpoint_text":"- Time from each open-label injection start to beginning of unequivocal symptom relief at all sites involved for subsequent attacks within 4 hours after injection","definition_or_measurement_approach":"Time from open-label injection to symptom relief at all involved sites for subsequent attacks within 4 hours."}
• {"endpoint_text":"- Time from each open-label injection start to complete resolution of subsequent attacks","definition_or_measurement_approach":"Time from open-label injection to complete resolution of subsequent attacks."}
• {"endpoint_text":"- Changes in symptom severity at the defining site by VAS rating from pre-injection over 4 hours after each IMP injection for repeated attacks","definition_or_measurement_approach":"Change in VAS rating from pre-injection to 4 hours after each IMP injection for repeated attacks."}
• {"endpoint_text":"- Occurrence of HAE attacks within 72 hours after pre-procedure injection","definition_or_measurement_approach":"Occurrence (yes/no) of HAE attacks within 72 hours following pre-procedure injection."}
• {"endpoint_text":"- Changes in QoL at the end of study compared with baseline","definition_or_measurement_approach":"Change in quality of life measures at end of study compared with baseline."}
• {"endpoint_text":"- Number and severity of adverse events (AEs)","definition_or_measurement_approach":"Count and severity grading of adverse events."}
• {"endpoint_text":"- Withdrawals due to AEs","definition_or_measurement_approach":"Number of participant withdrawals attributable to adverse events."}
• {"endpoint_text":"- Number and severity of AEs of special interest (AESIs), which comprise hypersensitivity, transmissible infectious agents, and AEs of the thromboembolic event (TEE) type","definition_or_measurement_approach":"Count and severity of AESIs including hypersensitivity, transmissible infectious agents, and TEE-type events."}
• {"endpoint_text":"- Changes in physical examination findings at the end of study compared with baseline","definition_or_measurement_approach":"Change in physical exam findings from baseline to end of study."}
• {"endpoint_text":"- Changes in vital signs from pre- to post-injection","definition_or_measurement_approach":"Change in vital sign measurements from pre-injection to post-injection assessments."}
• {"endpoint_text":"- Changes in laboratory parameters from pre- to post-injection","definition_or_measurement_approach":"Change in laboratory parameters from pre-injection to post-injection."}
• {"endpoint_text":"- Serology testing, blood nuclear antigen tests for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2, and parvovirus B19 at the end of study compared with baseline","definition_or_measurement_approach":"Serology and blood nuclear antigen testing for listed viruses at end of study compared with baseline."}
• {"endpoint_text":"- Presence of anti-C1-INH antibodies","definition_or_measurement_approach":"Assessment for presence of anti-C1-INH antibodies."}
• {"endpoint_text":"- Number and severity of local injection site reactions AEs","definition_or_measurement_approach":"Count and severity of local injection site adverse events."}
• {"endpoint_text":"- Number and severity of AEs reported within 7 days after a pre-procedure injection","definition_or_measurement_approach":"Count and severity of adverse events reported within 7 days after pre-procedure injection."}
• {"endpoint_text":"- The PK endpoint (for participants ≥2 to <18 years of age and a subset of 30 adults) is the effect of treatment on C1-INH activity, C1-INH antigen levels, and complement component 4 (C4) antigen levels. The area under the curve (AUC) over 1 week for C1-INH activity, uncorrected and corrected for baseline, will be used as the primary PK endpoints to be matched between adult and pediatric patients","definition_or_measurement_approach":"PK measures: C1-INH activity, C1-INH antigen levels, C4 antigen levels; AUC over 1 week for C1-INH activity (uncorrected and baseline-corrected) used as primary PK endpoints for matching adult and pediatric patients."}

Romania

Earliest CTIS Part Ii Submission Date

29-08-2023

Latest Decision Or Authorization Date

29-01-2024

Processing Time Days

153

Number Of Sites

1

Number Of Participants

4

Bulgaria

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

22-01-2025

Processing Time Days

233

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Austria

Contract research organisations

Name

Premier Research Group Limited

Responsibilities

Sponsor duties codes: 1,10,11,12,13,2,5,6,7,8

Name

Clinigen Clinical Supplies Management GmbH

Responsibilities

Sponsor duties codes: 14

Name

SGS Analytics Germany GmbH

Responsibilities

Sponsor duties codes: 4

Name

GxP Brain GmbH

Responsibilities

Sponsor duties codes: 3

Third parties

• {"country":"United Kingdom","full_name":"Premier Research Group Limited","duties_or_roles":"1,10,11,12,13,2,5,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"SGS Analytics Germany GmbH","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"GxP Brain GmbH","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}