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.: PACTR202010781639956 Date of Approval: 08/10/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title The impact of COVID-19 treatment on the type, strength and duration of antibody and cellular immune responses in SARS-CoV-2 patients in sub-Saharan Africa Ancillary Study of the ANTICOV Study: An open-label, multicentre, randomised, adaptive platform trial of the safety and efficacy of several therapies, including antiviral therapies, versus control in mild / moderate cases of COVID-19
Official scientific title The impact of COVID-19 treatment on the type, strength and duration of antibody and cellular immune responses in SARS-CoV-2 patients in sub-Saharan Africa
Brief summary describing the background and objectives of the trial Early treatment of viral infections can have immediate therapeutic effects but there is a risk of blunting the immune response and thus reducing the memory response to potential reinfection. Available data show that severe cases of COVID-19 have higher antibody levels than mild cases and asymptomatic SARS-coronavirus infections seem to elicit even lower levels. In addition to the strong focus on the humoral immune system in most studies, in particular serological testing and neutralizing antibodies, the role of cellular immunity against the current (SARS-Cov-2) and prior coronavirus outbreaks (MERS and SARS) is often partially neglected. First reports have observed that COVID-19 does not always results in detectable antibodies, let alone with neutralizing/protective properties, in particular in young adults . In addition to the strong focus on the humoral immune system in most studies, in particular serological testing and neutralizing antibodies, the role of cellular immunity against the current (SARS-Cov-2) and prior coronavirus outbreaks (MERS and SARS) is often partially neglected. First reports have observed that COVID-19 does not always results in detectable antibodies, let alone with neutralizing/protective properties, in particular in young adults . This indicates a key role for both the humoral and cellular immunity in resolving the disease . Likewise, research to date showed a severe lymphopenia and an exhausted T-cell phenotype in severe COVID-19 patients. In combination with its critical role in virus clearance and activation of antibody-producing B cells, T cells are argued to be important moderators of the COVID-19 disease. Our main aim is to assess the impact of (effective) COVID-19 treatment on the strength and duration of SARS-CoV-2-specific antibody and cellular immunity in mild / moderate COVID-19 patients across sub-Saharan Africa.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ANTICOV IMMUNO
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Covid-19
Purpose of the trial Treatment: Drugs
Anticipated trial start date 21/09/2020
Actual trial start date
Anticipated date of last follow up 30/09/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 1000
Actual target sample size (number of participants)
Recruitment status Completed
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
Parallel: different groups receive different interventions at same time during study Randomised Dynamic (adaptive) random allocation such as minimization Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Paracetamol One to two tablets every 4-6 hours as required, to a maximum of 6 tablets (3 grams) daily in divided doses Up to 14 days Oral route 250 Active-Treatment of Control Group
Experimental Group Hydroxychloroquine Day 1: loading dose of 800 mg daily, divided into two daily intakes of 400 mg taken 12 hours apart Day 2-7: maintenance dose of 400 mg daily, divided into two daily intakes of 200 mg taken 12 hours apart 7 days oral route 250
Experimental Group Lopinavir Ritonavir Day 1: loading dose of lopinavir 1600 mg / ritonavir 400 mg daily, divided into two daily intakes of lopinavir 800 mg / ritonavir 200 mg taken 12 hours apart Day 2-14: maintenance dose of lopinavir 800 mg / ritonavir 200 mg daily, divided into two daily intakes of lopinavir 400 mg / ritonavir 100 mg taken 12 hours apart 14 days Oral route 250
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
From the Master study : 1. Male or female patients, 2. Adults over or equal to 18 years of age at the time of screening. Children > 12 years of age may be included if recommended by the DSMB after the first analysis. 3. COVID-19 confirmed by molecular biology for SARS-Cov2 according to national guidelines, based on result within 24 hours prior to screening. 4. Viral syndrome with or without uncomplicated pneumonia, defined as blood oxygen saturation level (SpO2) over or equal to 94%. 5. Corrected QT interval (QTc – Bazett and Fridericia) < 480 msec on ECG. 6. Signed written consent from the patient or his/her representative. 7. Accepting and having the ability to be reached by telephone throughout the study. 8. Having designated a contact person who can be contacted in case of emergency. For the Immuno Ancillary study 1. Able and willing to provide consent for the immunological ancillary study 2. Able and willing to perform all study visits for a duration of 12 months after treatment start From the Master Study 1. Abnormal physical examination findings: • respiratory rate over or equal to 25 per minute; • blood pressure < 90/60 mmHg or > 160/100 mmHg; • body weight < 45 kg for patients over or equal to 18 years of age and age-adapted for children > 12 years of age if inclusion is recommended by the DSMB after the first analysis; • recurrent diarrhoea or vomiting episodes (> 3 in the last 24 hours) or hypokalaemia (< 3.5 mmol/L). 2. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency. 3. Feeling unwell for more than 7 days prior to screening. 4. Severe cardiopathy or history of arrhythmia, renal or liver insufficiency. 5. History of congenital or acquired long QT-interval, family history of long QT arrythmia, cardiac disease such as heart failure, myocardial infarction, family history of sudden cardiac death, sudden cardiac death, bradycardia < 50 bpm. 6. Past history of retinopathy, such as spots or dark strings floating in the field of vision (floaters), blurred or fluctuating vision, impaired colour vision, dark or empty areas in vision. 7. History of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. 8. End-organ compromise requiring admission to a resuscitation or continuous care unit or short-term life-threatening comorbidity with life expectancy < 3 months. 9. Pregnancy based on urine pregnancy test at screening or breast-feeding, unless recommended by the Data and Safety Monitoring Board after the first interim analysis. 10. Prior treatment with. lopinavir/ritonavir within 29 days prior to screening except if patients are receiving the same regimen as planned in this study. Patients randomised to lopinavir/ritonavir will stop their current treatment and switch to the IP lopinavir/ ritonavir. If randomised to other arms, patients will continue their current treatment with lopinavir/ritonavir. 11. Prior treatment with hydroxychloroquine within 29 days prior to screening or on-going at screening. 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 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 21/07/2020 Ministere de la sante publique comite national d ethique et de la sante Republique democratique du Congo CNES
Ethics Committee Address
Street address City Postal code Country
Immeuble PNMLS 1er Niveau local 5 Commune de Kasa-Vubu Kinshasa na Democratic Republic of the Congo
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1) Seroconversion for SARS-CoV-2 IgM, IgA and IgG by treatment arm and patient outcome Day 0, Day 7, Day 21, Month 1, Month 3, Month 6, Month 12
Primary Outcome 2) Quantitative levels of antibodies (IgM, IgG, IgA) specific for SARS-CoV-2 day 0, d7, d21, month1, M3, M6 and M12
Primary Outcome 3) Frequency of SARS-CoV-2-specific effector/memory CD4+ and CD8+ T cells Day 0, Day 21, Month 3, Month 6, Month 12
Primary Outcome 4) Proportions of (poly)functional SARS-CoV-2-specific T cells Day 0, Day 21, Month 3, Month 6, Month 12
Secondary Outcome 1) Epitope specificity of IgM, IgA and IgG isotypes targeting SARS-CoV-2 all visits
Secondary Outcome 2) Avidity index and neutralization activity (% neutralization or IC50) in selected participants and time points based on antibody levels and kinetics time points based on antibody levels and kinetics
Secondary Outcome 3) Quantitative levels of antibodies (IgM, IgG) against prevalent infections such as malaria and helminths, antibody levels against other respiratory infections, and medical history of TB, HIV and other known comorbidities (e.g. malnutrition). all visits
Secondary Outcome 4) Quantitative levels and seropositivity of antibodies (e.g. IgM, IgG, IgA) against coronaviruses circulating in participating countries all visits
Secondary Outcome 5) Positivity for SARS-CoV-2 in saliva (PCR/RDT) Month 1, Month 3, Month 6, Month 12
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Clinique Ngaliema Gombe Avenue Papa ILEO, ex des Cliniques Kinshasa, RDCongo BP3089 Kinshasa 3089 Democratic Republic of the Congo
Malabo Clinical Research Center Rotunda Arab Malabo Equatorial Guinea
Komfo Anokye Teaching Hospital KATH POBox 1934 Adum-Kumasi Kumasi Ghana
Kenyatta University Teaching Referral and Research Hospital Northern Bypass Rd Kahawa West Nairobi Kenya
University of Gondar Hospital Department of Internal Medicine, PO Box 196, Gondar Ethiopia
Centro de Investigacao e Treino em Saude da Polana Canico CISPOC Rua da Costa do Sol Polana Canico Maputo Mozambique
SOBA University Hospital Soba locality, South Khartoum, P.O Box 102, Khartoum, Sudan Khartoum Sudan
FUNDING SOURCES
Name of source Street address City Postal code Country
DNDi 15 Chemin Louis Dunant Geneva 1202 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor DNDi 15 Chemin Louis Dunant Geneva 1202 Switzerland Charities/Societies/Foundation
Primary Sponsor ITM Kronenburgstraat 43, 2000 Antwerpen, Belgium Antwerp 2000 Belgium Institute
Primary Sponsor ISGlobal Barcelona Institute for Gobal Health Hospital Clinical Universitat de Barcelona Carrer ROssello 132 Barcelona E-08036 Spain University
Primary Sponsor BERNHARD NOCHT INSTITUTE FOR TROPICAL MEDICINE Bernhard-Nocht-Strasse 74 Hamburg D-20359 Germany Institute
Primary Sponsor Ifakara Health Institute 463 Kiko avenue Box 78373 Dar-es-salaam, Tanzania Dar es salaam Tanzania Institute
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries James Arkinstall media@dndi.org +41229069230 15 chemin Louis Dunant
City Postal code Country Position/Affiliation
Geneva 1202 Switzerland Head of Communications and Advocacy
Role Name Email Phone Street address
Principal Investigator Nathalie StrubWourgaft nstrub@dndi.org +41229069246 15 Chemin Louis DUnant
City Postal code Country Position/Affiliation
Geneva 1202 Switzerland NTD DIrector
Role Name Email Phone Street address
Scientific Enquiries Gemma Moncunill gemma.moncunill@isglobal.org +34932275400 Carrer Rossello 153
City Postal code Country Position/Affiliation
Barcelona E-08036 Spain Assistant Research Professor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary Results will be shared after finalisation of the Clinical Study report Study Protocol 12 months within Clinical Study Report Finalisation OPen access
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