Resumen

Ensayo clínico prospectivo, multicéntrico, aleatorizado, doble ciego, de grupos paralelos, controlado con placebo, de eficacia y seguridad de fase 3 de un concentrado intravenoso de inhibidor de C1 esterasa (C1-INH) derivado de plasma humano en participantes con deficiencia congénita de C1-INH para el tratamiento y la prevención preprocedimiento de ataques agudos de angioedema hereditario.

Elegibilidad

Edad mínima: 2 YearsSexo: ALL

Criterios de inclusión

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)
Has confirmed diagnosis of HAE type I or II
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
Has a documented congenital C1-INH functional activity \<50% with or without C1-INH deficiency and C4 antigen level below the laboratory reference range
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
States willingness to comply with all study procedures and availability for the duration of the study
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). Highly effective methods of contraception:
Combined hormonal contraception (estrogens and progesterone) methods such as oral, implantable, intravaginal, injectable, or transdermal contraceptives at a stable dose for a minimum of 1 full cycle (hormonal contraceptives must inhibit ovulation) and for at least 4 weeks before screening
Progesterone only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
Intrauterine device
Intrauterine hormone-releasing system inserted at least 4 weeks before screening
Bilateral tubal ligation/occlusion or vasectomized partner (with surgical success confirmed by medical assessment) OR Agrees to abstain from heterosexual intercourse during study participation and to use a highly effective contraceptive (as described above) as backup if they become sexually active during the study. Abstinence is only acceptable if this is the participant's usual lifestyle. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception
Note: If a participant of CBP has a positive or suspected positive urine pregnancy test within 72 hours prior to treatment, a serum pregnancy test will be required
Male participants must not plan to father a child or donate sperm for 90 days after their last dose of study drug (for both blinded and open-label doses of the IMP). However, there are no official contraception requirements for male participants during the study.
Has confirmed QAT per definition criteria
Has a swelling episode that is new and not the continuation of a previous HAE attack

Criterios de exclusión

Has a history of clinically relevant antibody development against C1-INH
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)
Has a history of allergic reaction to C1-INH or other blood/plasma product
Has a history of B-cell malignancy that was unresolved in the past 5 years
Has a narcotic and/or alcoholic addiction
Has participated in any other investigational drug evaluation within 30 days before screening
Is pregnant or breastfeeding
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
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
(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)
Has received blood or a blood product for prophylactic or acute treatment with any C1-INH (Berinert®, Cinryze®, HAEgarda®, Ruconest®, etc.), non-biological bradykinin and kallikrein pathway inhibitors (e.g., ecallantide, icatibant, berotralstat), or treatment with tranexamic acid within 14 days before dosing with the IMP (or is not willing to abstain from these medications throughout the study)
started or changed hormone replacement therapy or selective estrogen receptor modulators (e.g., tamoxifen) within 14 days before IMP dosing
Started or changed androgen therapy (e.g. testosterone, dehydro- epiandrosterone/androstenedione, oxandrolone, danazol, stanozolol) within 14 days before IMP dosing or is not willing to maintain a stable dose throughout the study
Started or changed the dose of monoclonal antibodies e.g. lanadelumab within 11 weeks before dosing or not willing to maintain a stable dose throughout the study
Has used narcotic pain medications or non-opioid analgesics within 7 days before IMP dosing for a QAT
Has received OCTA-C1-INH within 14 days before IMP dosing
Has received blood or a blood product for prophylactic or acute treatment with any C1-INH (Berinert®, Cinryze®, HAEgarda®, Ruconest®, etc.), non-biological bradykinin and kallikrein pathway inhibitors (e.g., ecallantide, icatibant, berotralstat), or treatment with tranexamic acid within 14 days before dosing with the IMP (or is not willing to abstain from these medications throughout the study)
Is receiving hormone replacement therapy or selective estrogen receptor modulators (e.g., tamoxifen) and has had their dose changed within 14 days before IMP dosing
Is receiving or has received androgen therapy (e.g., testosterone, dehydroepiandrosterone/androstenedione, oxandrolone, danazol, stanozolol) IN ANY DOSE within 14 days before dosing
Started or changed the dose of monoclonal antibodies e.g lanadelumab within 11 weeks before dosing or not willing to maintain a stable dose throughout the study
Has used narcotic pain medications or non-opioid analgesics within 7 days before IMP dosing
Has received IMP within 14 days before IMP dosing
Has planned dental, medical, or surgical procedures during the PK Period that will require pre-procedural prevention

Intervenciones

drug

OCTA-C1-INH

OCTA-C1-INH is a stable, sterile, virus-inactivated, nano-filtered, highly purified concentrate of human C1-INH prepared from pooled human plasma. After reconstitution in 2.5mL water for injection, the solution can be administered as a slow IV injection. OCTA-C1-INH is given as a dose of 20 IU/kg body weight (BW)

other

Placebo

0.1 mL/kg BW 0.9% sodium chloride injection

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

OCTA-C1-INH

Placebo

Ubicaciones

Octapharma Research Site

Patrocinadores

Contactos

Patrick M Murphy