Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202106894720601 Date of Approval: 14/06/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title GBT2104-132
Official 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
Brief summary describing the background and objectives of the trial 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).
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Haematological Disorders,Infections and Infestations
Sub-Disease(s) or condition(s) being studied Sickle Cell Disease
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/07/2021
Actual trial start date
Anticipated date of last follow up 01/03/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 280
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Inclacumab 30mg/kg administered IV on Day 1 The total study duration for each participant will be variable based on the time from the start of the index VOC admission to Day 1. For example, if a participant begins screening at the start of a 10-day index VOC admission and is randomized the day of their index VOC resolution, the study duration would be 170 days, including a 10-day Screening period, a 90-day treatment period, and a 70-day (10 week) follow-up period. The inclacumab drug substance is manufactured by fermentation cell culture using Chinese hamster ovary (CHO) cells followed by purification. The drug substance and drug product are manufactured in accordance with Good Manufacturing Practice (GMP). Inclacumab drug product is a sterile, clear to opalescent liquid concentrate for infusion with an approximate pH of 5.5 provided in colorless, 10 mL single-use vials. Each vial contains 500 mg of inclacumab and the following excipients: L histidine-acetate, sucrose, and poloxamer 188. 140
Control Group Placebo Placebo administered IV on Day 1 as a single dose. 90-day treatment period The placebo for inclacumab to be used in this study will be a matched placebo for IV infusion with the same excipients found in inclacumab without the active product. 140 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
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. 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). Participant has experienced between 2 and 10 VOCs 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: a. Has no medically determined cause other than a vaso-occlusive event, and b. Results in a visit to a healthcare facility (hospital, emergency department, urgent care center, outpatient clinic, or infusion center) or results in a remote contact with a healthcare provider; and c. 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 test 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). 1. Participant is receiving regularly scheduled red blood cell (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. 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. 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 legal guardian unable/unlikely to comply with the study procedures. 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 12 Year(s) 85 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/07/2022 SCIENTIFIC AND ETHICS REVIEW UNIT SERU
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840-00200 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/07/2022 Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840-00200 Nairobi 00100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/12/2021 Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840-00200 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 23/07/2021 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840-00200 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/03/2022 Komfo Anokye Teaching Hospital Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
P.O. Box 1934 Kumasi 1934 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/07/2021 University of Zambia Biomedical Research Ethics committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway campus PO Box 50110 Lusaka 44370 Zambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 11/01/2022 ERES CONVERGE IRB
Ethics Committee Address
Street address City Postal code Country
Olive Tree Mean Wood road Lusaka Lusaka Zambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/01/2022 ERES CONVERGE IRB
Ethics Committee Address
Street address City Postal code Country
Olive Tree Mean Wood road Lusaka Lusaka Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary endpoint for this study is, following an index VOC, 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. 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 definition of the index VOC requiring admission is the same as the primary endpoint VOC requiring admission. To ensure consistency across study sites, all on-study VOCs reported by the study investigators will be adjudicated by an independent, blinded panel comprised of experts in SCD. The primary efficacy analysis will be performed on adjudicated data. Within 90 days of randomization
Secondary Outcome The secondary efficacy endpoints of the study are the following: • 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 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 (eg, parenteral narcotic agents or parenteral nonsteroidal anti-inflammatory drugs [NSAIDs]), or an increase in treatment with oral narcotics within 90 days following randomization. Within 90 days following randomization.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI CRDR Siaya Clinical Research Annex Siaya County Hospital Siaya 144-40600 Kenya
Hospital Henri Mondor 51 Avenue Marechal De Lattre De Tassigy Service Doncologie Medicale Creiteil 94010 France
American University of Beirut Medical Center American University of Beirut Medical Center Beirut 110236 Lebanon
St Jude Childrens Research Hospital 262 Danny Thomas PI Memphis 381053678 United States of America
Cairo University Paediatric Hospital abou El Reesh Hospital 123 Address Cairo Egypt
Zagazig University Hospitals Zagazig-Zagazig University El Zaqaziq 44519 Egypt
Alexandria University Hospital Champollion Street, Khartoum Square Alexandria Egypt
Al Kasr Al Ainy Cairo University Hospital Kasr Al Ainy University Hospital, Al Manial, Cairo Governorate Elmanial Egypt
Hospital Santa Marcelina Rua Santa Marcelina, 177 Sao Paulo 08270070 Brazil
University of Illinois at Chicago 1740 West Taylor Street Chicago 60612 United States of America
Duke University Medical Centre 40 Duke Medicine Cir Durham 277104000 United States of America
Ain Shams University Hospital Address unknown City Unknown Egypt
E O Ospedali Galliera Mura Delle Cappuccine, 14 Genova 16128 Italy
Hopital Avicenne 125 Rue de Stalingrad Bobigny 93009 France
University of South Alabama 5600 Girby Road Mobile 36693 United States of America
Arkansas Childrens Hospital 1 Childrens Way Little Rock 722023500 United States of America
University of Michigan 3912 Taubman Center,1500 East Medical Center Drive Ann Arbor 48109 United States of America
Mersin University Medical Faculty Ic Hastaliklari Anabilim Dali Mersin 33169 Turkey
Hospital Pablo Tobon Uribe Calle 78B 69 240 Cons. 309 Medellin 50034 Colombia
Centre Hospital Intercommunal 40 Avenue De Verdun, Department Dophtalmologie Creteil 94010 France
Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Avnida Brigadeiro Faria Lima, 5546 Sao Jose Do Rio Preto 15090000 Brazil
Hospital de Clinicas de Porto Alegre HCPA PPDS Rua Ramiro Barcelos, 2350 Porto Alegre 90035-003 Brazil
Nini Hospital Achier El Daya Tarablus Lebanon
Universitatsklinikum Regensburg Franz Josef StrauB Allee 11 Regensburg 93053 Germany
Baskent University Medical Faculty Adana Dr Turgut Noyan Practice and Research Center Dadaloglu Mah.2591 Sok. No4A Saricam 1250 Turkey
Organizacion Clinical Bonnadona Prevenir S.A.S Carrera 49C 82-70 Torre Adminitrativa Piso 2 Barranquilla 180020 Colombia
Childrens Healthcare of Atlanta 1001 Johnson Ferry Rd Atlanta 303421605 United States of America
Acibadem Adana Hospital Kazim Karaberik Mah. No 59 Denizli 1130 Turkey
Kings College Hospital Denmark Hill London SE5 9RS United Kingdom
University of Nigeria Kwame Nkuruma Way Enugu Nigeria
Lagos University Teaching Hospital Haematology PO Box 12003 Surulere 101014 Nigeria
University of Abuja Teaching Hospital PMB 117 Gwagwalada FCT Abuj Nigeria
National Hospital Abuj Central Business District Abuja Nigeria
Alexandria Clinical Research Center Champollion Street El-Khartoum Square Alexandria Egypt
Sultan Qaboos University Hospital 35 Alkoudh Al Khoudh 123 Oman
International Cancer Institute PO Box 8088 Eldoret Gpo 30100 Kenya
HEMORIO Unidade de Pesquisa Clinica Rua Frei Caneca, 80 - 325 Rio De Janeiro 20211-030 Brazil
Childrens Hospital Mansoura University El Gomhoureya Street El Dakahleya Al Mansoura 35516 Egypt
Komfo Anokye Teaching Hospital KATH Post Office Box 1934, Kumasi, Ashanti, Ghana , Office of Dean/Department of Child Health Kumasi Ghana
KEMRI CRDR Clinical Research Clinic Nairobi Off Hospital Road Nairobi 00100 Kenya
Kasr El Aini Hospital Address Unknown City Unknown Egypt
AOU Seconda Universita degli Studi di Napoli Primo Policlinico Via De Crecchio Napoli 80138 Italy
Clinica De La Costa PPDS Carrera 50 80-90 Barranquilla 80020 Colombia
Hacettepe Universitesi Tip Fakultesi Hastanesi Ahmet Adnan Saygun Main Street Ankara 6100 Turkey
Strathmore University Ole Sangale road, madaraka Nairobi 59857 Kenya
International Cancer Institute P.O. Box 8088 Eldoret 30100 Kenya
The University Teaching Hospital Childrens Hospital RW 1X , Nationalist Road Lusaka 10101 Zambia
Arthur Davison Childrens Hospital Corner Chiwanangala and Boundary Roads, Northrise Ndola 10101 Zambia
Matero Clinical Research Site Chitimukulu Rd Matero 10101 Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
Global Blood Therapeutics Inc 181 Oyster Point Blvd South San Francisco 94080 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Global Blood Therapeutics Inc 181 Oyster Point Blvd South San Francisco CA 94080 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Dr Miguel Abboud American University Of Beirut Medical Center Beirut 11-0236 Lebanon
Dr Pablo Bartolucci 51 Avenue Marechal De Lattre De Tassigny Service Doncologie Medicale Creteil 94010 France
Dr Jeremie Estepp 262 Danny Thomas Pl Memphis 38105-367 United States of America
Dr Amal ElBeshlawy 123 Address Cairo Egypt
Dr Mohamed Badr Zagazig Zagazig University El Zaqaziq 44519 Egypt
Dr Hoda Hassab Champollion Street, Khartoum Square Alexandria Egypt
Dr Mervat Mattar Kasr Al Ainy University Hospital ,Al Manial, Cairo Governorate Elmanial Egypt
Dr Rita de Cassia Cavalheiro Rua Santa Marcelina, 177 Sao Paulo 08270-070 Brazil
Dr Santosh Saraf 1740 West Talylor Street Chicago 60612 United States of America
Dr Nirmish Shah 40 Duke Medicine Cir Durham 27710-400 United States of America
Dr Fatma Ebeid Ain Shams University Hospital Al Qahirah Egypt
Dr Gian Luca Forni Mura Delle Cappuccine, 14 Genova 16128 Italy
Dr Sylvain Le Jeune 125 Rue de Stalingrad Bobigny 93009 France
Dr Chibuzo Ilonze 5600 Girby Road Mobile 36693 United States of America
Dr Carolyne Suzanne Saccente 1 Childrens Way Little Rock 72202-350 United States of America
Dr Sharon Singh 3912 Taubman Center, 1500 East Medical Center Drive Ann Arbor 48109 United States of America
Dr Selma Unal Ic Hastaliklari Anabilim Dali Mersin 33169 Turkey
Dr Kenny Galves Calle 78B 69 240 Cons. 309 MEDELLIN 50034 Colombia
Dr Corinne Pondarre 40 Avenue De Verdun, Departement Dophtalmologie Creteil 94010 France
Dr Alexandre Lorenzetti Avenida Brigadeiro Faria Lima, 5546 Sao Jose Do Rio Preto 15090-000 Brazil
Dr Joao Ricardo Friedrisch Rua Ramiro Barcelos, 2350 Porto Alegre 90035-003 Brazil
Dr Adlette Inati Achier El Daya Tarablus Lebanon
Dr Katharina Kleinschmidt Franz-Josef-StrauB-Allee 11 Regensburg 93053 Germany
Dr Hakan Ozdogu Dadaloglu Mah2591 Sok No 4A Saricam 1250 Turkey
Dr Marla Saenz Rojas Carrera 49 C 82-70 Torre Administrativa Piso 2 BARRANQUILLA 180020 Colombia
Dr Robert Clark Brown 1001 Johnson Ferry Rd Atlanta 30342-160 United States of America
Dr Ali Bulent Antmen Kazim Karabekir Mah No 59 Denizli 1130 Turkey
Dr Moji Awogbade Denmark Hill London SE5 9RS United Kingdom
Dr Iheanyi Okpala Kwame Nkuruma Way Enugu Nigeria
Dr Adeseye Akinsete Lagos University Teaching Hospital Haematology Surulere 101014 Nigeria
Dr Obiageli Nnodu University of Abuja Teaching Hospital Abuja Nigeria
Dr Oluseyi Oniyangi Central Business District Abuja Nigeria
Dr Ashraf ElGhandour Champollion Street El-Khartoum Square Alexandria Egypt
Dr Salam AlKindi Sultan Qaboos University Hospital Al Khoudh 123 Oman
Dr Yasser Wali Sultan Qaboos University Hospital Al Khoudh 123 Oman
Dr Frederick Chite International Cancer Institute Eldoret Gpo 30100 Kenya
Dr Patricia Moura Rua Frei Caneca 08 - 325 Rio De Janeiro 20211-030 Brazil
Dr Videlis Nduba Siaya County Hospital Siaya 144-40600 Kenya
Dr Ahmed Mansour El Gomhoureya Street El. Dakahleya Al Mansoura 35516 Egypt
Dr Alex OseiAkoto Office of Dean Department of Child Health Kumasi Ghana
Dr Videlis Nduba Off hospital road Nairobi 0100 Kuwait
Dr Mona Hamdy Mahmoud Kasr El Aini Hospital Al Qahirah Egypt
Dr Silverio Perrotta Via De Crecchio Napoli 80138 Italy
Dr Fausto Vitali Carrera 50 Barranquilla 80020 Colombia
Dr Sule Unal Ahmet Adnan Saygun Main Street Ankara 6100 Turkey
Dr. Chunda Liyoka Nationalist Road Lusaka 10101 Zambia
Dr. Mwansa Jonathan Corner Chiwanangala and Boundary Roads, Northrise Ndola 10101 Zambia
Dr. Roma Chilengi Off Alick Nkhata Road Lusaka 10101 Zambia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Videlis Nduba vnduba@gmail.com +254724522474 KEMRI CRDR Clinical Research Clinic Nairobi, Off Hospital Road, PO Box 47855-00100
City Postal code Country Position/Affiliation
Nairobi 144-40600 Kenya Medical Doctor
Role Name Email Phone Street address
Public Enquiries Margot Hottmann mhottmann@gbt.com +0016508228728 181 Oyster Point Blvd
City Postal code Country Position/Affiliation
South San Francisco CA 94080 United States of America Senior Clinical Trial Manager
Role Name Email Phone Street address
Scientific Enquiries Carolyn Hoppe choppe@gbt.com +0016508228728 181 Oyster Point Blvd
City Postal code Country Position/Affiliation
South San Francisco CA 94080 United States of America Senior Director Medical Affairs
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Trial result summaries will be shared when the final clinical study report is available. The method of sharing the information is still to be determined across the entire program if studies. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol When the Clinical Study Report is final. To be confirmed.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information