PET Imaging of Vaso-Occlusive Crisis (VOC) in SCD

Enrico Novelli

Status and phase: Enrolling; Phase 1

Conditions: Sickle Cell Disease

Treatments: Drug: Cu-64]-LLP2A; Radiation: Positron Emission Tomography

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04925492

R01HL154629 (U.S. NIH Grant/Contract)

STUDY20020135

Details and patient eligibility

About

The purpose of this study is to find objective biomarkers of vaso-occlusion (blood vessel blockage) in people with SCD. Using information from earlier studies and work being done, researchers have developed a strategy to image VOC, using positron emission tomography (PET).

The ability to see and measure VOC in SCD patients can help patient care, by showing when and how a VOC is occurring or going to occur. Studying this method will also help in future drug research, as it will allow researchers to deliver promising new medications that target hyper-adhesion and sickling in people with SCD.

Full description

The purpose of this study is to find objective biomarkers of vaso-occlusion (blood vessel blockage) in people with Sickle Cell Disease(SCD). Using information from earlier studies, and work being done at Washington University, a strategy to image vaso-occulusive crisis (VOC) has been developed, using positron emission tomography (PET) for anatomical localization only. 64Cu-LLP2A is the radio tracer used for the study.

Aim: To develop quantitative PET imaging of VOC in patients with SCD. The researchers hypothesize that the radio tracer 64Cu-LLP2A uptake increases proportionally to the intensity of pain in patients with VOC, compared to baseline values. This increase in uptake will be assessed focally in areas of pain as well as globally to reflect heightened systemic inflammation.

Primary and secondary study endpoint: The overarching hypothesis of this study is that PET tracer uptake of intensity of 64Cu-LLP2A is a real time, quantitative measure of hyper adhesion in VOC.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a confirmed diagnosis of SCD (HbSS, SC, S/β-thalassemia, SD, SE, SO) by hemoglobin electrophoresis/High Performance Liquid Chromatography (HPLC)
• Aged 18 and above
• Ability to understand and provide informed consent.
• If receiving hydroxyurea or L-glutamine, crizanlizumab, voxelotor or erythropoietin stimulating agents, must have been receiving the drug for at least 12 weeks prior to screening and plan to continue taking the drug at the same dose and schedule during the study
• Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to screening visit as determined by medical history.

Exclusion criteria

• Active malignancy
• Current pregnancy or breast feeding
• Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted
• Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to screening visit or plans to participate in another investigational drug trial

Trial design

Primary purpose: Screening

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

20 participants in 2 patient groups

Finding Optimal Scan Timing

Experimental group

Description:

Group A will receive two PET scans after the radiotracer injection to learn the best timing of the scan for the rest of the people in the study during participant's baseline state. Participants will receive another injection of the radiotracer during a sickle cell crisis and have one PET scan. Receive an optional injection and perform another PET scan 12 months after your sickle cell crisis if there were technical problems the previous scans.

Treatment:

Radiation: Positron Emission Tomography

Drug: Cu-64]-LLP2A

Scan at Determined Optimal Timepoint

Experimental group

Description:

Group B participants will receive an injection of the radiotracer and undergo only one PET scan during a baseline state. Participants will receive another injection of the radiotracer during a sickle cell crisis and have one PET scan. Receive an optional injection and perform another PET scan 12 months after your sickle cell crisis if there were technical problems the previous scans.

Treatment:

Radiation: Positron Emission Tomography

Drug: Cu-64]-LLP2A