Safety of Single Doses of CSL889 in Adult Patients With Sickle Cell Disease

CSL Behring

Status and phase

Completed

Phase 1

Conditions

Sickle Cell Disease

Treatments

Biological: CSL889

Study type

Interventional

Funder types

Industry

Identifiers

NCT04285827

CSL889_1001

2019-001870-27 (EudraCT Number)

Details and patient eligibility

About

This is a phase 1, first-in-human, multi-center, open-label, single dose cohort study to evaluate the safety and tolerability, pharmacokinetics (PK), exploratory pharmacodynamics (PD), and biomarkers of target engagement of CSL889 following single intravenous (IV) doses in subjects with sickle cell disease (SCD). The study involves sequential dose escalation of cohorts with between-group assessments of key safety and PK variables.

Enrollment

28 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of SCD as documented in the subject's medical record
Aged 18 to 60 years, inclusive
Stable SCD for at least 30 days before Day 1. Stable SCD is defined as the subject being at his or her medical baseline, with no evidence of worsening of disease over the last 30 days (including VOC, recent major surgery, hospitalization, serious infection, significant bleeding, cerebrovascular accident, seizures, or IV opioids)(Part A)
Uncomplicated VOC requiring parenteral opioid treatment and admission to hospital for management. Uncomplicated VOC is defined as sickle cell pain without the following associated clinical features (Part B):
- Fever (> 38.5 °C)
- Hypotension (< 90/60 mmHg)
- Hypoxia (< 90% oxygen saturation on room air, or requiring oxygen therapy to maintain oxygen saturation above 90%)
- New neurological signs and / or symptoms clinically suggestive of stroke or transient ischemic attack
- Signs and / or symptoms of Acute Chest Syndrome, accompanied by any new pulmonary infiltrate on chest radiography (chest X-ray to be performed if clinically indicated and according to local clinical guidelines)
Subject is either not taking one of the study permitted SCD therapies (hydroxyurea, L-glutamine, L-glutaminecrizanlizumab, and/or voxelotor) or subject has been taking one or more of those for at least 30 days before Day 1 and is on a stable, well tolerated regimen that is planned to continue without change throughout the study

Exclusion criteria

History of primary hemorrhagic stroke
History or evidence of inherited bleeding diathesis or significant coagulopathy at risk for bleeding
Weight >110 kg (242 lbs)
Surgery within 30 days before Day 1 or any preplanned surgeries during the study (minor surgeries may be permitted under local anesthesia before screening, with permission of the medical monitor)
Female subjects who are pregnant or breastfeeding
Female subject of childbearing potential or fertile male subject either 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 CSL889.
Treatment with any other drug / biologic that is newly approved for SCD during the conduct of this study within 90 days before Day 1. Exceptions: crizanlizumab [Adakveo®] and voxelotor [Oxbryta®] ] are permitted (where prescribed).
Treatment with another investigational product within 30 days or within 5 half-lives of the product (whichever is greater) before Day 1
Vaccination within 30 days before Day 1, or planned vaccination during the study
Body-mass index < 16 kg/m2 or weight < 50 kg (110 lbs)
History of anaphylactic-type reactions, transfusion related reaction, asthma, or autoimmune disease

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

28 participants in 8 patient groups

CSL889 Cohort A1 (Dose 1)

Experimental group

Description: