Evaluation of Safety, Efficacy, and Pharmacokinetics of CSL889 (Human Hemopexin) in Sickle Cell Disease Patients Experiencing Vaso-Occlusive Crisis

The primary objective of this study is to evaluate the **safety** and tolerability of CSL889, a human hemopexin, when administered via intravenous infusion in individuals experiencing a vaso-occlusive crisis (VOC) associated with **sickle cell disease** (SCD). Additionally, the study aims to assess the effect of CSL889 on the time to resolution of VOC in these patients. This is clinically relevant as VOC is a significant complication of SCD, leading to severe pain and potential organ damage, and effective management can improve patient outcomes.

The clinical trial involves a total of **184 participants** diagnosed with **sickle cell disease** experiencing a vaso-occlusive crisis. The study population includes both male and female subjects, with an age range of 12 years and older. Participants are selected based on their presentation at the study site with a new acute vaso-occlusive crisis requiring treatment with parenteral opioids. The trial includes both adults and adolescents, where enrollment for adolescents is contingent upon approval by the sponsor and endorsement by the Independent Data Monitoring Committee. The study population is characterized by a vulnerable group, given the nature of the disease and the acute condition being studied. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the safety, efficacy, and pharmacokinetics of CSL889, a **solution for infusion** containing **human hemopexin**, in adults and adolescents experiencing a vaso-occlusive crisis due to **sickle cell disease**. The trial is structured as a Phase 2/3 adaptive study, with the primary objective of assessing the time to resolution of the vaso-occlusive crisis, defined as the time to discontinuation of parenteral opioids. Secondary endpoints include hospital admission rates, length of hospital stay, and the percentage of participants experiencing acute chest syndrome, acute kidney injury, or stroke.

The trial is expected to commence recruitment on July 7, 2025, and conclude by April 4, 2028. Participants will be involved in the study for a maximum treatment period of 5 days, during which they will receive either CSL889 or a placebo via **intravenous** infusion. The maximum daily dose of CSL889 is 10 grams, with a total maximum dose of 30 grams over the treatment period. The study includes several key visits: an initial screening visit to confirm eligibility, multiple follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess overall outcomes and collect final data.

Inclusion criteria require participants to be at least 12 years old, diagnosed with sickle cell disease of any genotype, and presenting with a new acute vaso-occlusive crisis necessitating treatment with parenteral opioids. Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or if the study is terminated early for any reason. The trial aims to provide comprehensive data on the safety and potential therapeutic benefits of CSL889 in managing vaso-occlusive crises in this patient population.

The clinical trial involves the administration of **Hemopexin, Human**, an experimental medication, to evaluate its safety, efficacy, and pharmacokinetics in individuals with sickle cell disease during a vaso-occlusive crisis. The investigational product, identified by the sponsor product code CSL889, is formulated as a **solution for infusion**. The active substance, **hemopexin, human**, is a protein derived from other sources, and is also known by synonyms such as Human hemopexin and Human beta-1B-glycoprotein. The medication is administered intravenously, with a maximum daily dose of 10 grams and a total maximum dose of 30 grams over a treatment period not exceeding 5 days. The study is designed to monitor participant compliance with the dosing schedule to ensure accurate assessment of the drug's effects.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is also presented as a solution for infusion but contains no active substance. The use of a placebo is critical in maintaining the study's integrity by providing a baseline to compare the effects of the investigational drug. The administration of the placebo follows the same route and schedule as the experimental medication to ensure consistency across treatment groups.

The efficacy of CSL889 in the treatment of **sickle cell disease** during vaso-occlusive crisis will be assessed using several primary and secondary endpoints. The primary efficacy endpoint is the time to resolution of vaso-occlusive crisis, defined as the time to discontinuation of parenteral opioids. Secondary endpoints include hospital admission rate, length of hospital stay, percentage of participants experiencing acute chest syndrome, acute kidney injury, or stroke, and opioid consumption. Additionally, pharmacokinetic parameters such as maximum observed concentration (Cmax), area under the concentration-time curve (AUCtau), time of maximum concentration (Tmax), and trough concentration (Ctrough) after doses of CSL889 will be evaluated.

Data collection will involve measuring these endpoints at specified timepoints throughout the study. The study is designed as a multicenter, randomized, multiple-dose, double-blind, placebo-controlled adaptive trial. The efficacy assessments will be conducted using validated scales and laboratory tests where applicable. The analysis will focus on comparing the outcomes between the treatment group receiving CSL889 and the placebo group to determine the therapeutic benefit of CSL889 in managing vaso-occlusive crises in participants with sickle cell disease.