Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents with Sickle Cell Disease during Vaso-Occlusive Crisis

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] - Hemic and Lymphatic Diseases [C15]

Trial duration

25 Jun 2025 → 2 Dec 2025

Decision date (initial)

2025-04-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The main objectives of this study are to evaluate the safety and tolerability of CSL889 administered by intravenous (IV) infusion in study subjects, and to evaluate the effect of CSL889 (human hemopexin) on time to resolution of vaso-occlusive crisis (VOC) in participants with sickle cell disease (SCD).

Secondary objectives 1

1. 0

Conditions and MedDRA coding

Sickle cell disease vaso-occlusive crisis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003333-PIP01-22

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 1

1. At the time of informed consent: >= 18 years of age (adults); or >= 12 to less than (<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee [IDMC]). •Diagnosed with SCD (any genotype). •Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.

Exclusion criteria 1

1. "• VOC pain onset greater than or equal to (>=) 72 hours before administration of first parenteral opioid (Part A; may be adjusted for Part B based on prespecified analysis). • Must not have a history of greater than (>) 5 VOCs requiring hospital admission in the past 6 months; or signs and / or symptoms of ACS; or new neurological symptoms suggestive of acute stroke or transient ischemic attack; or any stage (acute kidney injury) AKI; or been discharged from inpatient hospital admission for VOC or other vaso-occlusive event within 14 days before the current presentation. •Serum hemoglobin < 6 g/dL, serum ferritin >= 2000 ng/mL, receiving an approved medication for SCD that has not been on a stable, well-tolerated regimen, currently taking methadone or buprenorphine."

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Time to resolution of VOC (time to discontinuation of parenteral opioids)
2. Number of participants with treatment-emergent adverse events (TEAEs)
3. Percentage of participants with TEAEs
4. Number of participants with detectable treatment emergent (TE) anti-CSL889 antibodies
5. Percentage of participants with detectable TE anti-CSL889 antibodies

Secondary endpoints 17

1. Hospital admission rate
2. Length of hospital stay (If hospitalized)
3. Percentage of participants experiencing acute chest syndrome (ACS), acute kidney injury (AKI), or stroke
4. Length of acute care stay
5. Total Length of acute care and hospital stay
6. Re-presentation rate to an acute care facility for VOC or ACS after discharge
7. Hospital admission rate for VOC or ACS after discharge
8. Opioid consumption
9. Percentage of participants with >=30% pain reduction by NRS score
10. Maximum observed concentration (Cmax) after Doses 1 and 3 of CSL889
11. Area under the concentration (AUCtau) after Doses 1 and 3 of CSL889
12. Time of maximum concentration (Tmax) after Doses 1 and 3 of CSL889
13. Trough concentration (Ctrough) after each dose of CSL889
14. Accumulation ratio (AR) for AUCtau of CSL889 (the ratio between the AUCtau of Doses 3 and 1)
15. AR for Cmax of CSL889 (the ratio between the Cmax of Doses 3 and 1)
16. AR for Ctrough of CSL889 (the ratio between the Ctrough of the last dose and Dose 1)
17. Ctrough after each dose in sparse PK subset of CSL889

Investigational products

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

Test 1

Placebo 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

Study Director

Public contact point

Organisation

CSL Behring LLC

Contact name

Trial Registration Coordinator

Third parties 18

Locations

7 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Results and documents

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

Documents 152 files

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

Application history

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