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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CSL Behring LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

15 Jun 2021 → 21 Nov 2025

Decision date (initial)

2024-05-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

CSL Behring LLC

External identifiers

EU CT number

2024-510777-18-00

EudraCT number

2020-003918-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Prophylaxis, Efficacy, Pharmacodynamic

The primary objective of the study is to evaluate the long-term safety of SC administration of CSL312 in the prophylactic treatment of subjects with C1-INH HAE

Secondary objectives 1

1. The secondary objectives of this study are to evaluate the long‑term efficacy, safety and patient reported assessment of response to therapy The secondary objectives of this study are to evaluate the long‑term efficacy, safety and patient reported assessment of response to therapy

Conditions and MedDRA coding

Hereditary angioedema

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002726-PIP01-19

Plan to share IPD

Yes

IPD plan description

CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at [email protected].

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 6

1. 1. Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema or recurrent angioedema associated with urticaria
2. 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. 3. Use of monoclonal antibodies such as lanadelumab (Takhzyro®) 3 months before the first day of the Run-in Period.
4. 4. Female subjects use estrogen-containing oral contraceptives or hormone replacement therapy within 4 weeks prior to screening
5. 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. 6. Pregnant, breastfeeding, or not willing to cease breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Number of subjects with treatment emergent adverse events (TEAEs)
2. 2. Percentage of subjects with TEAEs
3. 3. TEAEs rates per injection
4. 4. TEAEs rates per subject year

Secondary endpoints 9

1. 1. The time-normalized number (per month and year) of Hereditary Angioedema (HAE attacks) for the entire study.
2. 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. 3. The time-normalized number (per month and year) of HAE attacks requiring on-demand treatment in subjects on treatment.
4. 4. The time-normalized number (per month and year) of moderate and/or severe HAE attacks in subjects on treatment
5. 5. Number and percentage of subjects rating their response to therapy as good or excellent.
6. 6. The number and percentage of subjects experiencing TEAEs with CSL312.
7. 7. The number and percentage of subjects experiencing adverse events of special interest (AESIs) with CSL312.
8. 8. The number and percentage of subjects experiencing serious adverse events (SAEs), including deaths, with CSL312.
9. 9. The number and percentage of subjects experiencing CSL312 induced anti-CSL312 antibodies with CSL312.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CSL Behring LLC

Sponsor organisation

CSL Behring LLC

Address

1020 1st Avenue

City

King Of Prussia

Postcode

19406-1310

Country

United States

Scientific contact point

Organisation

CSL Behring LLC

Contact name

Trial Registration Coordinator

Public contact point

Organisation

CSL Behring LLC

Contact name

Trial Registration Coordinator

Third parties 14

Locations

5 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 90 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications