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

• ClinicalTrials.gov Identifier: NCT01895361
• Recruitment Status: Completed
• First Posted: July 10, 2013
• Results First Posted: January 31, 2020
• Last Update Posted: January 31, 2020
• Sponsor: Reprixys Pharmaceutical Corporation
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Food and Drug Administration (FDA)
• Information provided by (Responsible Party): Reprixys Pharmaceutical Corporation

Tracking Information

• First Submitted Date: July 3, 2013
• First Posted Date: July 10, 2013
• Results First Submitted Date: December 12, 2019
• Results First Posted Date: January 31, 2020
• Last Update Posted Date: January 31, 2020
• Study Start Date: July 2013
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 21, 2020)

• Annual Rate of Sickle Cell-related Pain Crises (SCPC) Per Hodges-Lehmann Median [ Time Frame: One year ]
  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.
• Annual Rate of Sickle Cell-related Pain Crises (SCPC) - Per Standard Median [ Time Frame: One year ]
  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.

• Original Primary Outcome Measures (submitted: July 9, 2013): Rate of sickle cell-related pain crises [ Time Frame: One year ]

Current Secondary Outcome Measures (submitted: January 21, 2020)

• Annual Rate of Days Hospitalized (Key Secondary Endpoint) Per Hodges-Lehmann Median [ Time Frame: One year ]
  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).
• Time to First Sickle Cell-related Pain Crisis [ Time Frame: Up to one year ]
  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.
• Time to Second Sickle Cell-related Pain Crisis [ Time Frame: Up to one year ]
  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.
• Annual Rate of Uncomplicated Sickle Cell-related Pain Crisis Per Hodges-Lehmann Median [ Time Frame: Up to one year ]
  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.
• Annual Rate of Acute Chest Syndrome Per Hodges-Lehmann Median [ Time Frame: One year ]
  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.
• Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire [ Time Frame: Baseline, Day 15, Week 14, Week 26, Week 38, Week 52, and Week 58, up to 58 weeks ]
  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.

Original Secondary Outcome Measures (submitted: July 9, 2013)

• Rate of sickle cell-related pain crises by concomitant hydroxyurea use [ Time Frame: One year ]
• Time to first sickle cell-related pain crisis [ Time Frame: Up to one year ]
• Time to second sickle cell-related pain crisis [ Time Frame: Up to one year ]
• Number of hospitalization days per year [ Time Frame: Up to one year ]
• Absolute change from baseline in hemoglobin [ Time Frame: One year ]
• Absolute change from baseline in lactate dehydrogenase [ Time Frame: One year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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)

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sickle Cell Disease

Intervention

• Drug: SelG1
• Drug: Placebo

Study Arms

• Experimental: High-dose SelG1 (Selg1 5.0 mg/kg)
  IV Infusion, once every 4 weeks through Week 50
  Intervention: Drug: SelG1
• Experimental: Low-dose SelG1 (Selg1 2.5 mg/kg)
  IV Infusion, once every 4 weeks through Week 50
  Intervention: Drug: SelG1
• Placebo Comparator: Placebo
  IV Infusion, once every 4 weeks through Week 50
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 12, 2016): 198
• Original Estimated Enrollment (submitted: July 9, 2013): 174
• Actual Study Completion Date: March 2016
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Jamaica, United States

Administrative Information

• NCT Number: NCT01895361
• Other Study ID Numbers: SelG1-00005; R44HL093893 ( U.S. NIH Grant/Contract ); R01FD004805 ( U.S. FDA Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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.

• URL: https://www.clinicalstudydatarequest.com

• Current Responsible Party: Reprixys Pharmaceutical Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Reprixys Pharmaceutical Corporation
• Original Study Sponsor: Same as current

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• Food and Drug Administration (FDA)

• Investigators: Not Provided
• PRS Account: Reprixys Pharmaceutical Corporation
• Verification Date: January 2020