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Trial details
A Randomized, Double-blind, Placebo-controlled, Multicenter Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises
Current status:
Approved
|
Date registered:
06/06/2022
Trial version(s)
History: 24/06/2021
History: 24/06/2021
Current: 24/06/2021
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Main Information
Primary registry identifying number
LBCTR2021074831
Protocol number
GBT2104-132
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
15/06/2021
Primary sponsor
Global Blood Therapeutics, Inc.
Primary sponsor: Country of origin
USA
Public title
A Randomized, Double-blind, Placebo-controlled, Multicenter Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises
Acronym
Scientific title
A Randomized, Double-blind, Placebo-controlled, Multicenter Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises
Acronym
Brief summary of the study: English
This is a Phase 3, randomized, double-blind, placebo-controlled, 2-arm, multicenter, parallel-group study. The primary objective of this study is to evaluate the safety and efficacy of a single dose of inclacumab compared to placebo to reduce the incidence of re-admission to a healthcare facility for a vaso-occlusive crisis (VOC) after an admission for an index VOC in participants with sickle cell disease (SCD). Additional objectives of the study are to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of inclacumab, the presence of anti-drug antibodies (ADAs), and changes in quality of life (QOL).
Brief summary of the study: Arabic
هذه هي دراسة في المرحلة الثالثة متعددة المراكز، عشوائية التوزيع، مزدوجة التعمية، مراقبة بدواء وهمي الهدف الأساسي من هذه الدراسة هو تقييم سلامة وفعالية جرعة واحدة من inclacumab مقارنةً بالدواء الوهمي لتقليل حدوث إعادة القبول في مرفق الرعاية الصحية لأزمة انسداد الأوعية الدموية (VOC) بعد القبول لمؤشر VOC. في المشاركين المصابين بمرض فقر الدم المنجلي (SCD). تتمثل الأهداف الإضافية للدراسة في تقييم الحرائك الدوائية (PK) والديناميكا الدوائية (PD) لـ inclacumab ، ووجود الأجسام المضادة للأدوية (ADAs) ، والتغيرات في نوعية الحياة (QOL).
Health conditions/problem studied: Specify
Patients with a diagnosis of sicke cell disease who have experienced between 2 and 10 vaso-occlusive crises in the 12 months preceding enrollment and have been hospitalized for an index vaso-occlusive crises.
Interventions: Specify
This study will be a randomized, placebo-controlled, double-blind, multicenter, parallel-group study to assess the safety and efficacy of a single dose of inclacumab in reducing the rate of re-admission to a healthcare facility for a VOC after an index VOC. The index VOC is any VOC that required admission to a healthcare facility and treatment with parenteral pain medication where the admission includes: • A hospital admission, or • An admission to an emergency room, observation unit, or infusion center for ≥ 12 hours, or • 2 visits to an emergency room, observation unit, or infusion center over a 72-hour period. for an acute episode of pain with no other cause other than a vaso-occlusive event that includes the following: • Uncomplicated VOC, • Acute chest syndrome (ACS), • Acute hepatic sequestration, • Acute splenic sequestration, or • Priapism. The study will include approximately 280 adult and adolescent participants (≥ 12 years of age) with SCD. Initial enrollment will include participants ≥ 16 years of age until the Data Monitoring Committee (DMC) recommends to the Sponsor that adequate safety and PK data support the enrollment of participants 12 to 15 years of age. Participants will be randomized with a 1:1 ratio into one of two treatment arms (140 participants per arm) as follows: • Inclacumab 30 mg/kg administered intravenously (IV); or • Placebo administered IV. Randomization may occur up to 5 days after the index VOC has resolved, as assessed by the Investigator (for example, hospital discharge, completion of parenteral analgesia, or transition to oral analgesics). On the day of randomization (Day 1), participants will receive a single dose of study drug. At the time of randomization, participants will be stratified by Baseline hydroxyurea (HU) use (yes; no), number of VOCs (2 to 4; 5 to 10) in the preceding 12 months, and geographic region (North America; rest of world). An independent DMC will regularly review the totality of accumulated safety data from all ongoing inclacumab studies on an ongoing, unblinded basis, with specific emphasis on adolescent participants. Details will be provided in the DMC Charter. Participants that complete the study through Day 90 will be provided the opportunity to enroll in an open-label extension (OLE) study.
Key inclusion and exclusion criteria: Inclusion criteria
Inclusion Criteria 1. Participant has an index VOC. The index VOC is any VOC that required admission to a healthcare facility and treatment with parenteral pain medication. An admission for the index VOC includes: a. A hospital admission, or b. An admission to an emergency room, observation unit, or infusion center for ≥ 12 hours, or c. 2 visits to an emergency room, observation unit, or infusion center over a 72-hour period. for an acute episode of pain with no other cause other than a vaso-occlusive event that includes the following: • Uncomplicated VOC, • Acute chest syndrome (ACS), • Acute hepatic sequestration, • Acute splenic sequestration, or • Priapism. 2. Participant has a confirmed diagnosis of SCD (any genotype). Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing at Baseline. 3. Participant is male or female, ≥ 12 years of age at the time of informed consent. NOTE: Initial study enrollment will include only participants ≥ 16 years of age until the DMC recommends to the Sponsor that adequate safety and PK data support the enrollment of participants 12 to 15 years of age. Sites will be informed by the Sponsor when participants 12 to 15 years of age may be enrolled. 4. Participant is able to complete screening and receive study drug within 5 days following investigator-assessed resolution of index VOC (for example, hospital discharge, discontinuation of parenteral pain medication, or transition to oral pain medication). 5. Participant has experienced between 2 and 10 VOCs (inclusive) within the 12 months prior to Screening as determined by documented medical history. The index VOC is not to be considered as one of the 2 to 10 events. A prior VOC is defined as an acute episode of pain that: • Has no medically determined cause other than a vaso-occlusive event, and • Results in a visit to a medical facility (hospital, emergency department, urgent care center, outpatient clinic, or infusion center) or results in a remote contact with a healthcare provider; and • Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. 6. Participants receiving erythropoiesis-stimulating agents (ESA, eg, erythropoietin [EPO]) must be on a stable dose for at least 90 days prior to Screening and expected to continue with the stabilized regimen throughout the course of the study. 7. Participants receiving HU, L-glutamine, or voxelotor must be on a stable dose for at least 30 days prior to Screening and expected to continue with the stabilized regimen throughout the course of the study. 8. Participant has adequate venous access, in the opinion of the Investigator, to comply with study procedures. 9. Participant understands the study procedures and agrees to participate in the study by giving written informed consent or parental permission/written assent 10. Women of childbearing potential (WOCBP) are required to have a negative serum pregnancy test at the Screening Visit and negative urine pregnancy tests on all subsequent clinic visits and must agree to use a highly effective method of contraception throughout the study period and for at least 165 days after dosing. Female participants will not be considered of childbearing potential if they are pre-menarchal, surgically sterile (hysterectomy, bilateral salpingectomy, tubal ligation, or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause, confirmed by follicle-stimulating hormone test results).
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
12
Key inclusion and exclusion criteria: Age maximum
90
Key inclusion and exclusion criteria: Exclusion criteria
Exclusion Criteria Candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening or Baseline visits or at the timepoint specified in the individual criterion listed. 1. Participant is receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion). 2. Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days prior to Screening. 3. Participant weighs > 133 kg (292 lbs.). 4. Participant has a significant active and poorly controlled (unstable) hepatic disorder clearly unrelated to SCD. 5. Participant has any of the following laboratory values at Screening: a. Absolute neutrophil count (ANC) < 1.0 × 109/L b. Platelet count < 80 × 109/L c. Hemoglobin < 4.0 g/dL for adults and < 5.0 g/dL for participants ages 12 to < 18 years of age d. Estimated glomerular filtration rate (eGFR) < 30 mL/min using Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula in adults, and Schwartz formula in adolescents. NOTE: Laboratory assessments conducted during Screening may be done by the local laboratory and must include at least a CBC with total and differential leukocyte count, platelet count, and hemoglobin, a chemistry panel with creatinine, and a serum pregnancy test to assess participant eligibility. Laboratory assessments conducted during the index VOC admission that are obtained within 7 days prior to screening may be used for Screening assessments if done as part of standard medical care. 6. Participant has known active (symptomatic) COVID infection or tests positive for COVID-19 at any time during their index admission. 7. Participant has a history of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to Screening including severe or unstable pulmonary hypertension. 8. Participant has had treatment for a malignancy within the 12 months prior to Screening (except non-melanoma skin cancer and in situ cervical cancers). 9. Participant has had a stroke within the 2 years prior to the Screening Visit. 10. Participant has a positive test indicative of active malaria infection at Screening. Testing to be conducted at local laboratories in malaria-endemic regions at the discretion of the Investigator. 11. Participant has any confirmed clinically significant drug allergy and/or known hypersensitivity to monoclonal antibody therapeutics or formulation components of the study drug or a related drug. 12. Participant has been treated with another investigational agent within 30 days or 5 half-lives of the investigational agent (whichever is greater) prior to Screening. 13. Participant has had a major surgery within 8 weeks prior to the Screening Visit. 14. Participant is pregnant, breastfeeding, or planning to become pregnant during the 90-day treatment period. 15. Participant, parent, or legal guardian are unlikely to comply with the study procedures. 16. Participant has other medical, or psychological, or behavioral conditions that, in the opinion of the Investigator, would: confound or interfere with evaluation of safety, efficacy, and/or PK of the investigational drug; prevent compliance with the study protocol; preclude informed consent; or render the participant, parent, or caretaker unable/unlikely to comply with the study procedures.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Safety
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
Inclacumab
Type of IMP
Immunological
Pharmaceutical class
Inclacumab is a recombinant human monoclonal antibody (huMAb) of the immunoglobulin (Ig)G4 subclass directed against human P-selectin, which is being developed by Global Blood Therapeutics, Inc. (GBT), for the treatment of sickle cell disease (SCD). Inclacumab binds to P-selectin, which is a cell adhesion molecule produced by endothelial cells and platelets. Upon activation of these cells (e.g., by thrombin, cytokines, complement components, hypoxia, and heme), P-selectin is translocated to the cell surface where it binds to its primary ligand P-selectin glycoprotein ligand-1 (PSGL-1) and mediates leukocytes recruitment by platelets or endothelial cells. The same mechanism is also responsible for abnormal rolling and adhesion of sickle red blood cells (RBC) to the endothelium, initiating acute vascular occlusion and chronically impairing microvascular blood flow in patients with SCD. Inclacumab binding of P-selectin and prevention of P-selectin binding to its ligands is the putative mechanism by which inclacumab prevents the binding of sickle RBCs or leukocytes to endothelium
Therapeutic indication
sickle cell disease (SCD)
Therapeutic benefit
Inclacumab is a recombinant huMAb of the IgG4 subclass directed against human P-selectin. The molecule is composed of two heterodimers, each composed of a heavy and a light polypeptide chain. The four polypeptide chains are linked together by disulfide bonds. To avoid antibody-dependent cell-mediated cytotoxicity and to improve structural stability, two single point mutations (L235E, S228P) were introduced into the Fc part of the molecule. The inclacumab drug substance is manufactured by fermentation cell culture using Chinese hamster ovary (CHO) cells followed by purification. The drug substance, drug product, and placebo are manufactured in accordance with Good Manufacturing Practices (GMP). Results from the SUSTAIN trial in patients with SCD showed that treatment with crizanlizumab, a humanized antibody to P-selectin, resulted in a significantly lower rate of sickle cell-related pain crises (i.e., VOC) than placebo. These data validated P-selectin as a therapeutic target for SCD disease. Inclacumab is currently not approved by any health authority for the treatment of patients with any disease. Inclacumab is being developed to reduce the risk of vaso-occlusive crises in patients with SCD.
Biospecimen retention
Samples with DNA**
Biospecimen description
optional genomic samples will be retained beyond study completion
Target sample size
280
Actual enrollment target size
Date of first enrollment: Type
Actual
Date of first enrollment: Date
13/12/2021
Date of study closure: Type
Actual
Date of study closure: Date
11/12/2023
Recruitment status
Recruiting
Date of completion
11/03/2024
IPD sharing statement plan
Yes
IPD sharing statement description
Patient's full identity will not be on any of the study documents or sample collected and kept by the sponsor for their studies. Only the partial date of birth will be only collected. Only a unique participant number for the study will link the data or samples to the patients.
Additional data URL
https://clinicaltrials.gov/ct2/show/NCT04927247
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
N.A
N.A
Sources of Monetary or Material Support
Name
Global Blood Therapeutics, Inc
Secondary Sponsors
Name
N.A
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Aziz
Zoghbi
MCT-CRO, Berytech Technology and Health, 5th Floor Damascus Road, Beirut, Lebanon
Lebanon
009617100 8269
aziz.zoghbi@mct -cro.com
Director of Country Oversight and Manageme nt MENA, Gulf and Africa
Scientific
Miguel
Abboud
American University of Beirut Medical Center, Cairo Street, Hamra, Beirut, Lebanon
Lebanon
009613534 213
ma56@aub.edu.l b
PI
Scientific
Adlette
Inati
Nini Hospital, el Maarad Street, Triploli, Lebanon
Lebanon
009613228 033
adlette.inati@lau. edu.lb
PI
Scientific
Carolyn
Hoppe
181 Oyster Point Blvd. South San Francisco, CA 94080, USA
United States of America
+1 510.289.90 97
choppe@gbt.com
Medical Monitor
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Nini Hospital
Adlette Inati
Professor of Pediatric Hematology and Oncology
Approved
American University of Beirut Medical Center
Miguel Abboud
Professor of Pediatric Hematology and Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
10/01/2022
Dr. Miguel Abboud
ma56@aub.edu.lb
+9613534213
Nini Hospital
23/06/2021
Dr. Adlette Inati
adlette.inati@lau.edu.lb
+9613228033
Countries of Recruitment
Name
Lebanon
United States of America
Health Conditions or Problems Studied
Condition
Code
Keyword
Sickle Cell Disease
Sickle-cell disorders (D57)
SCD, vaso-occlusive crisis, blood disorders, hemoglobin, red blood cells, sickle-like shape, mutation in hemoglobin gene, sickle-cell trait, sickle-cell crisis, Sickle Cell Disease SCD, Hydroxyurea/ Hydroxycarbamide Therapy, SCA
Interventions
Intervention
Description
Keyword
Inclacumab
Participants will be randomized with a 1:1 ratio into one of two treatment arms (140 participants per arm) as follows: • Inclacumab 30 mg/kg administered intravenously (IV); or • Placebo administered IV. Randomization may occur up to 5
Treatment
Primary Outcomes
Name
Time points
Measure
Index VOC requiring admission
the proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 90 days of randomization
An admission for a VOC includes: A hospital admission, or an admission to an emergency room, observation unit, or infusion center for ≥ 12 hours, or 2 visits to an emergency room, observation unit, or infusion center over a 72-hour period
Change in Laboratory assessments
at each visit
Complete blood count, chemistry and coagulation
Key Secondary Outcomes
Name
Time points
Measure
Time to first VOC
90 days of randomization
Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 90 days of randomization
Proportion of participants with at least 1 VOC
30 days of randomization
Proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 30 days of randomization.
Rate of VOCs leading to a healthcare visit (hospital, emergency room, clinic visit, or remote contact with a healthcare provider) that requires parenteral pain medication
Within 90 days of randmization
Rate of VOCs leading to a healthcare visit (hospital, emergency room, clinic visit, or remote contact with a healthcare provider) that requires parenteral pain medication (eg, parenteral narcotic agents or parenteral nonsteroidal anti-inflammatory drugs [NSAIDs]), or an increase in treatment with oral narcotics within 90 days following randomization.
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial