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

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

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)

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Placebo; Drug: SelG1

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
  • São Paulo, Brazil
  • Bahia
    • Salvador, Bahia, Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
  • São Paulo
    • Campinas, São Paulo, Brazil
    • São José do Rio Preto, São Paulo, Brazil
• Jamaica
  • Kingston, Jamaica
• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Mobile, Alabama, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Los Angeles, California, United States
    • Oakland, California, United States
    • Orange, California, United States
    • Sacramento, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • Connecticut
    • New Haven, Connecticut, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Daytona Beach, Florida, United States
    • Jacksonville, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Augusta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
    • Peoria, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Kentucky
    • Louisville, Kentucky, United States
  • Louisiana
    • Baton Rouge, Louisiana, United States
    • New Orleans, Louisiana, United States
  • Maryland
    • Baltimore, Maryland, United States
    • Bethesda, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Detroit, Michigan, United States
  • Mississippi
    • Jackson, Mississippi, United States
  • Missouri
    • Kansas City, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • New Brunswick, New Jersey, United States
    • Newark, New Jersey, United States
  • New York
    • Bronx, New York, United States
    • Brooklyn, New York, United States
    • New Hyde Park, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
    • Durham, North Carolina, United States
    • Greenville, North Carolina, United States
  • Ohio
    • Cleveland, Ohio, United States
    • Columbus, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States
    • Sumter, South Carolina, United States
  • Texas
    • Fort Worth, Texas, United States
    • Houston, Texas, United States
  • Virginia
    • Norfolk, Virginia, United States
    • Richmond, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High-dose SelG1 (Selg1 5.0 mg/kg); IV Infusion, once every 4 weeks through Week 50	Drug: SelG1
EXPERIMENTAL: Low-dose SelG1 (Selg1 2.5 mg/kg); IV Infusion, once every 4 weeks through Week 50	Drug: SelG1
PLACEBO_COMPARATOR: Placebo; IV Infusion, once every 4 weeks through Week 50	Drug: Placebo

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

Collaborators and Investigators

• Sponsor: Reprixys Pharmaceutical Corporation
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Food and Drug Administration (FDA)

Publications and helpful links

General Publications

• Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439. doi: 10.1056/NEJMoa1611770. Epub 2016 Dec 3.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): March 1, 2016
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: July 3, 2013
• First Submitted That Met QC Criteria: July 9, 2013
• First Posted (ESTIMATE): July 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: priapism; monoclonal antibody; sickle cell disease; SCD; P-selectin; sickle cell anemia; sickle cell; pain crisis; vaso-occlusion; SelG1; pain crises; vasoocclusion; hepatic sequestration; splenic sequestration; chest syndrome
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: SelG1-00005; R44HL093893 (NIH); R01FD004805 (FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No