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An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema

Long-term safety and efficacy of CSL312 (garadacimab) in the prophylactic treatment of hereditary angioedema attacks

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

JPN-CHIKEN@csl.com.au

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

+81-3-4213-0191

JPN-CHIKEN@csl.com.au

Not Recruiting

Oct. 01, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

prevention purpose

1. Males and females aged >= 12 years
2. Diagnosed with clinically confirmed C1-INH HAE
3. Experienced >= 3 HAE attacks during the 3 months before Screening
4. Participated in the Run-in Period for at least 1 month (CSL312-naive subjects only)
5. Experienced at least an average of 1 HAE attack per month during the Run-in Period

1. Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema or recurrent angioedema associated with urticaria
2. Use of C1-INH products, androgens, antifibrinolytics or other small molecule medications for routine prophylaxis against HAE attacks at least 2 weeks before the first day of the Run-in Period
3. Use of monoclonal antibodies such as lanadelumab (Takhzyro(R)) 3 months before the first day of the Run-in Period.
4. Female subjects use estrogen-containing oral contraceptives or hormone replacement therapy within 4 weeks prior to screening
5. Female or male subjects who are fertile and sexually active not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 30 days after receipt of the last dose of CSL312
6. Pregnant, breastfeeding, or not willing to cease breastfeeding

Both

Hereditary Angioedema

Subcutaneous injection of Factor XIIa antagonist monoclonal antibody (CSL312) 200 mg

1. Number of subjects with treatment emergent adverse events (TEAEs)
2. Percentage of subjects with TEAEs
3. TEAEs rates per injection
4. TEAEs rates per subject year
(Time point of evaluation: up to 45 months)

Long-term efficacy (time point of evaluation: up to 43 months months):
1. The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study
2. The percentage reduction and the number of subjects experiencing at least >= 50%, >= 70%, >= 90 or equal to 100% (attack free) reduction in the time-normalized number of HAE attacks on Treatment compared to Run-in Period
3. The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment
4. The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment
5. The number and percentage of subjects rating their response to therapy as good or excellent

Long-term safety (time point of evaluation: for up to 45 months):
6. The number and percentage of subjects experiencing TEAEs
7. The number and percentage of subjects experiencing adverse events of special interest (AESIs)
8. The number and percentage of subjects experiencing TEAEs for naive C1-INH subjects only
9. The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths
10. The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies

Aug. 24, 2021

Yes

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available. Supporting Materials: Protocol and Statistical Analysis Plan will be availale. Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website. Access Criteria: Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee. An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee. The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

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