Study to Assess Safety and Impact of SelG1 With or Without Hydroxyurea Therapy in Sickle Cell Disease Patients With Pain Crises

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to determine whether the investigational drug SelG1 when given to sickle cell disease patients either taking or not taking hydroxyurea was effective in preventing or reducing the occurrence of pain crises. SelG1 prevents various cells in the bloodstream from sticking together. By stopping these cell-cell interactions, SelG1 may prevent small blood vessels from becoming blocked and therefore reduce the occurrence and severity of pain crises. Other effects of SelG1 was evaluated, as well as the safety of the drug and how long it stayed in the blood stream. Funding Source - FDA Office of Orphan Products Development (OOPD)

Official Title
-----------------
A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Blind, 12-Month Study to Assess Safety and Efficacy of SelG1 With or Without Hydroxyurea Therapy in Sickle Cell Disease Patients With Sickle Cell-Related Pain Crises

Conditions
-----------------
Sickle Cell Disease

Intervention / Treatment
-----------------
* Drug: SelG1
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Sickle Cell Disease (HbSS, HbSC, HbSβ⁰-thalassemia, or HbSβ⁺-thalassemia) If receiving hydroxyurea or erythropoietin, treatment must have been prescribed for at least 6 months, with the dose stable for at least 3 months Between 2 and 10 sickle cell-related pain crises in the past 12 months Key Exclusion Criteria: On a chronic transfusion program or planning on exchange transfusion during the study Hemoglobin <4.0 g/dL Planned initiation, termination, or dose alteration of hydroxyurea during the study Receiving chronic anticoagulation therapy (e.g. warfarin, heparin) other than aspirin

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-dose SelG1 (Selg1 5.0 mg/kg)<br>IV Infusion, once every 4 weeks through Week 50 | Drug: SelG1<br> <br> |
| Experimental: Low-dose SelG1 (Selg1 2.5 mg/kg)<br>IV Infusion, once every 4 weeks through Week 50 | Drug: SelG1<br> <br> |
| Placebo Comparator: Placebo<br>IV Infusion, once every 4 weeks through Week 50 | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Rate of Sickle Cell-related Pain Crises (SCPC) Per Hodges-Lehmann Median | An SCPC is defined as an acute episode of pain with no other medically determined cause than a vasoocclusive event that requires a medical facility visit and treatment with oral or parenteral narcotics, or parenteral non-steroidal anti-inflammatory drugs. The annual rate of SCPC is defined as the total number of pain crises for a patient occurring from the date of randomization to the end date multiplied by 365 divided by the number of days during that same time period. End date is defined as the last dose date plus 14 days. For participants never dosed, the end date was the end of study date. This calculation accounts for early dropouts or lost to follow-up by extrapolating the SCPC rate of every participant to one year. | One year | 
| Annual Rate of Sickle Cell-related Pain Crises (SCPC) - Per Standard Median | An SCPC is defined as an acute episode of pain with no other medically determined cause than a vasoocclusive event that requires a medical facility visit and treatment with oral or parenteral narcotics, or parenteral non-steroidal anti-inflammatory drugs. The annual rate of SCPC is defined as the total number of pain crises for a patient occurring from the date of randomization to the end date multiplied by 365 divided by the number of days during that same time period. End date is defined as the last dose date plus 14 days. For participants never dosed, the end date was the end of study date. This calculation accounts for early dropouts or lost to follow-up by extrapolating the SCPC rate of every participant to one year. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Rate of Days Hospitalized (Key Secondary Endpoint) Per Hodges-Lehmann Median | The annual rate of days hospitalized was calculated as the number of days hospitalized multiplied by 365 divided by the end date minus the date of randomization plus one where the end date is defined as the last dose date plus 14 days (for subjects never dosed, the end date equaled the end of study date, which was the last site contact for these patients). | One year | 
| Time to First Sickle Cell-related Pain Crisis | Time to first SCPC is defined as months from randomization to first SCPC. A participant without SCPC before withdrawal or completion of the study is considered censored at the time of the end date. End date is defined as the last dose plus 14 days. For participants never dosed, the end date is the end of study date. | Up to one year | 
| Time to Second Sickle Cell-related Pain Crisis | Time to second SCPC is defined as months from randomization to second SCPC. A patient with less than two SCPC before withdrawal or completion of the study is considered censored at the time of the end date. End date is defined as the last dose plus 14 days. For patients never dosed, the end date is the end of study date. | Up to one year | 
| Annual Rate of Uncomplicated Sickle Cell-related Pain Crisis Per Hodges-Lehmann Median | Uncomplicated SCPC is defined as an acute episode of pain with no known cause for pain other than a vasoocclusive event; requiring a visit to a medical facility; and requiring treatment with a parenteral or oral narcotic (including opiates), or parenteral NSAIDs; but is NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. | Up to one year | 
| Annual Rate of Acute Chest Syndrome Per Hodges-Lehmann Median | Acute Chest Syndrome (ACS) is defined on the basis of the finding of a new pulmonary infiltrate involving at least one complete lung segment that was consistent with alveolar consolidation, but excluding atelectasis (as indicated by chest X-ray). At least one of the following additional signs or symptoms needs to be present as well: a participant had to have reported chest pain, a temperature of more than 38.5oC, tachypnea, wheezing or cough. | One year | 
| Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | The BPI instrument was completed by the patients at pre-specified study visits prior to & during the Treatment & Follow-Up Evaluation Phases. Patients completed the brief pain inventory long-form, 1-week recall at the indicated pre-specified study visits. The BPI is a standardized self-reported questionnaire developed to provide information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI also asks questions about pain relief, pain quality, & the patient's perception of the cause of pain. Since pain can be quite variable over a day, the BPI asks patients to rate their pain at the time of responding to the questionnaire (pain now), & also at its worst, least, & average over the previous week. The scorings for pain & interference have a range from 0 (no pain/no interference) to 10 (worst pain/complete interference). The BPI scoring manual was used to calculate scores for each domain. | Baseline, Day 15, Week 14, Week 26, Week 38, Week 52, and Week 58, up to 58 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
P-selectin, SelG1, monoclonal antibody, sickle cell disease, sickle cell anemia, sickle cell, pain crisis, pain crises, vasoocclusion, vaso-occlusion, priapism, hepatic sequestration, splenic sequestration, chest syndrome, SCD