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.: PACTR202106511293049 Date of Approval: 17/06/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title GBT2104-131
Official scientific title A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Safety and Efficacy of Inclacumab in Participants with Sickle Cell Disease Experiencing 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 treatment every 12-weeks with inclacumab to reduce the incidence of VOCs in participants with SCD. Additional objectives of the study are to evaluate the PK and PD of inclacumab, the presence of anti-drug antibodies (ADAs), and changes in quality of life (QOL). This study uses placebo as a comparator on the background of standard of care (SOC) treatment for a VOC. Placebo was chosen as the control because it is necessary to determine the safety and efficacy of inclacumab by allowing efficacy to be estimated controlling for background VOCs with SOC and safety signals to be distinguished from AEs occurring due to SCD. Treatments with stable standard of care are allowed including stable doses of HU, erythropoietin stimulating agents (ESAs), voxelotor, and L-glutamine. However, initiation of these agents during screening or after randomization and use of crizanlizumab for 90 days prior and during the study is prohibited. Crizanlizumab has a similar mechanism of action that would confound interpretation of this study. All other standard therapeutic interventions for SCD (eg, hydration, analgesia, acute transfusions) are allowed under this protocol. Randomization to placebo treatment in this study does not place study participants at increased risk, as the SOC (other than the use of crizanlizumab) for patients with VOCs will be provided during the study.
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 01/06/2021
Actual trial start date
Anticipated date of last follow up 31/10/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 240
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 30 mg/kg administered IV Q12W 48-week treatment period This study is a randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of inclacumab compared to placebo when administered once every 12 weeks (Q12W) (Day 1, Week 12, Week 24 and Week 36) to patients with a diagnosis of SCD who have experienced between 2 and 10 VOCs in the 12 months preceding enrollment in this study. Given the long half-life of inclacumab (terminal half-life of 21 to 28 days) at the dose to be evaluated in this study, the majority of participants receiving active study drug are expected to maintain target concentrations through Week 48. The primary endpoint of the study is the rate of VOCs occurring over a 48-week treatment period. The safety of treatment with inclacumab over the 48-week period will also be assessed. This study builds on experience from previous clinical studies in patients with SCD in reducing the incidence of VOCs. A placebo-controlled trial represents the most common and acceptable approach for determining the safety and efficacy for a therapeutic through a well-designed, controlled study. Some notable distinctions from prior studies include the definition of a VOC that allows for telemedicine in addition to the previous definitions which required a visit to a healthcare facility. This distinction has been incorporated based on the changes in treatment practices that have occurred as a result of the COVID-19 pandemic. Patients with SCD are less likely to visit a healthcare facility and are more frequently reaching out to their healthcare provider for pain medication changes/prescriptions (McFarling, 2020; Powell, 2020). Even though patients are not making as many visits to a healthcare facility for a VOC, the telemedicine visit nonetheless represents a crisis on the part of the patient that requires intervention by a healthcare practitioner. Use of a telemedicine-based VOC is therefore justified. 120
Control Group Placebo IV 30mg/kg 48 weeks treatment Placebo 120 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Participant has a confirmed diagnosis of SCD (HbSS, HbSC, HbSβ0 thalassemia, or HbSβ+ thalassemia genotype). Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening. 2. Participant is male or female, ≥ 12 years of age at the time of informed consent. NOTE: Initial study enrollment will include participants ≥ 16 years of age until the DMC determines 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. 3. Participant has experienced between 2 and 10 VOCs within the 12 months prior to the Screening Visit as determined by documented medical history. A prior VOC is defined as an acute episode of pain which:  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. 4. Participants receiving erythropoiesis-stimulating agents (ESA, eg, erythropoietin [EPO]) must be on a stable dose for at least 90 days prior to the Screening Visit and expected to continue with the stabilized regimen throughout the course of the study. 5. Participants receiving HU, L-glutamine, or voxelotor must be on a stable dose for at least 30 days prior to the Screening Visit and expected to continue with the stabilized regimen throughout the course of the study. 6. Participant has adequate venous access, in the opinion of the Investigator, to comply with study procedures. 7. Participant understands the study procedures and agrees to participate in the study by giving written informed consent or parental permission/written assent. 8. 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 RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion). 2. Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days prior to the Screening Visit 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 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 during Screening. 7. Participant has a history of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including severe or unstable pulmonary hypertension. 8. Participant has had treatment for a malignancy within the 12 months prior to the Screening Visit (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 malariaendemic 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 in another investigational trial within 30 days or 5 half-lives of the investigational agent (whichever is greater) prior to the Screening Visit. 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 48-week treatment period. 15. Participant, parent, or legal guardian are unlikely to comply with the study procedures. 16. Participant has other medical, or psychological, or addictive condition 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. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 12 Year(s) 65 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 05/05/2021 Zagazig University Faculty of Medicine Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
KM 28 Cairo Ismailia Road Ahmed Orabi District El Zagazig 44519 Egypt
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 20/04/2022 KEMRI 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 20/04/2022 KEMRI 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 07/12/2021 KEMRI 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 08/06/2021 Gertrudes Childrens Home
Ethics Committee Address
Street address City Postal code Country
P.O Box 34, Muthaiga road 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 27/10/2021 KEMRI SERU
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 26/10/2021 National Institute for Medical Research Tanzania
Ethics Committee Address
Street address City Postal code Country
P.O. Box 9653 11101 Dar es Salaam -3 Barack Obama Drive Dare es Salam 11101 Tanzania
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 24/02/2022 Komfo Anokye Teaching Hospital Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
Kumasi Ghana 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 09/07/2021 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 efficacy endpoint for the study is the rate of VOCs during the 48-week treatment period. A 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 (hospitalization, 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. Complicated VOCs of acute chest syndrome (ACS), hepatic sequestration, splenic sequestration, and priapism that meet the requirements listed above will be included in the primary endpoint. To ensure consistency across study sites, all VOCs identified will be adjudicated by an independent, blinded panel comprised of experts in SCD. The primary efficacy analysis will be performed on adjudicated data. During the 48-week period
Secondary Outcome The secondary efficacy endpoints for the study are the following:  Time to first VOC during the 48-week treatment period.  Time to second VOC during the 48-week treatment period.  Proportion of participants with no VOCs during the 48-week treatment period. Rate of VOCs that required admission to a healthcare facility and treatment with parenteral pain medication during the 48-week treatment period where 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, or  Number of days of inpatient hospitalization for a VOC during the 48-week treatment period. During the 48-week period
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
Brigham and Womens Hospital 75 Francis Street Boston 2115 United States of America
Cairo University Paediatric Hospital about 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
Duke University Medical Center 40 Duke Medicine Cir Durham 277104000 United States of America
Indiana Hemophilia and Thrombosis Center 8326 Naab Rd Indianapolis 462601920 United States of America
Mersin University Medical Faculty Ic Hastaliklari Anabilim Dali Mersin 33169 Turkey
University of South Alabama Children and Women Hospital 1601 Center St Ste 1280 Mobile 36604 United States of America
General Hospital of Larisa Tsakalof 1 Larissa 41221 Greece
Sociedad de Oncologia y hematologia del Cesar Ltda Carrera 15 14 91 Valledupar 200001 Colombia
Nini Hospital Achier El Daya Tarablus Lebanon
Basket University Medical Faculty Adana Dr. Turgut Noyan Practice and Research Center Dadaloglu Mah.2591 Sok. No4/A Saricam 1250 Turkey
Organizacion Clinica Bonnadona Prevenir S.A.S Carrera 49C 82-70 Torre Administrativa Piso 2 Barranquilla 180020 Colombia
Childrens Healthcare of Atlanta 1001 Johnson Ferry Rd Atlanta 303421605 United States of America
Acibadem Adana Hospital Kazim Karabekir Mah. No 59 Denizli 1130 Turkey
University of Nigeria Kwame Nkuruma Way Enugu Nigeria
Alexandria Clinical Research Center Champollion Street El-Khartoum Square Alexandria Egypt
Sultan Qaboos University Hospital 35, Alkoudh Al Khoudh 123 Oman
Childrens Hospital Mansoura University El Gomhoureya Street El. Dakahleya Al Monsoura 35516 Egypt
KEMRI CRDR Clinical Research Clinic Nairobi Off hospital road Nairobi Kenya
Cairo University Faculty of Medicine 417, 4th Touristic Area, 6 October Guiza 97661 Egypt
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
Gertrudes Childrens Home 34 Muthaiga Rd Nairobi 00100 Kenya
International Cancer Institute ICI P.O Box 8088 Eldoret 30100 Kenya
Strathmore University Ole Sangale rd Nairobi 00200 Kenya
NIMR Mbeya Medical Research Center Hospital Hill Road Dar es Salam 53107 Tanzania
Komfo Anokye Teaching Hospital KATH Post Office Box 1934, Kumasi, Ashanti, Ghana. Ashanti Ghana
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 CA 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 Maureen Achebe 75 Francis Street, Heart Vascular Center Boston Massachusetts 2115 United States of America
Dr Almal ElBeshlawy 123 Address Cairo Al Qahirah 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 Nirmish Shah 40 Duke Medicine Cir Durham 27710-400 United States of America
Dr Sylvain Le Jeune 125 Rue de Stalingrad Bobigny 93009 France
Dr Brandon Hardesty 8326 Naab Rd Indianapolis 46260-192 United States of America
Dr Selma Unal Ic Hastaliklari Anabilim Dali Mersin 33169 Turkey
Dr Kenny Galvez Calle 78B 69 240 Cons. 309 Medellin 50034 Colombia
Dr Chibuzo Ilonze 1601 Center St Ste 1280 Mobile 36604 United States of America
Dr Carmen Rosales Carrera 15 14 91 Valledupar 200001 Colombia
Dr Adlette Inati Achier El Daya Tarablus Lebanon
Dr Hakan Ozdogu Dadaloglu Mah2591 Sok 4/A Saricam 1250 Turkey
Dr Marla Saenz Carrera49 C82-70 Torre Administrativa Piso 2 Barranquilla 180020 Colombia
Dr Robert Brown 1001 Johnson Ferry Rd Atlanta 30342-160 United States of America
Dr Ali Bulent Antmen Kazim Karabekir Mah.59 Denizli 1130 Turkey
Dr Iheanyi Okpala Kwame Nkuruma Way Enugu Nigeria
Dr Ashraf ElGhandour Champollion Street El-Khartoum Square Alexandria Egypt
Dr Salam Alkindi 35, Alkoudh Al Khoudh 123 Oman
Dr Yasser Wali 35, Alkoudh Al Khoudh 123 Oman
Dr Videlis Nduba Siaya County Hospital Siaya 144-40600 Kenya
Dr Ahmed Mansour El Gomhoureya Street El. Dakahleya Al Mansoura 35516 Egypt
Dr Videlis Nduba Off hospital road Nairobi 00100 Kenya
Dr Mona Hamdy Mahmoud 417, 4th Touristic Area, 6 October Guiza 97661 Egypt
Dr Fausto Vitali Carrera 50, 80-90 Barranquilla 80020 Colombia
Dr Sule Unal Ahmet Adnan Saygun Main Street Ankara 6100 Turkey
Dr Alex Osei Akoto Office of Dean Department of Child Health Kumasi Ghana
Dr. Bernhards Ogutu Ole Sangale road Nairobi 00200 Kenya
Dr. Jessie Githanga P O Box 34 Muthaiga Road Nairobi 00100 Kenya
Dr. Fredrick Chite Asirwa P.O. Box 8088 Nandi Road Eldoret 30100 Kenya
Dr. Chunda Liyoka Nationalist Rd Lusaka 10101 Zambia
Jonathan Mwansa 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 Kenya Medical Doctor
Role Name Email Phone Street address
Public Enquiries Kalyan Obalampalli kobalampalli@gbt.com +2579162840777 181 Oyster Point Blvd.
City Postal code Country Position/Affiliation
South San Francisco CA 94080 United States of America Global Blood Therapeutics Inc.
Role Name Email Phone Street address
Scientific Enquiries Carolyn Hoppe choppe@gbt.com +0016507417741 181 Oyster Point Blvd.
City Postal code Country Position/Affiliation
South San Francisco CA 94080 United States of America Sr. 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 of 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