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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202407739287108 Date of Registration: 29/07/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Mosaic HIV-1 Envelope Trimer Immunogens Administered to People Living With HIV (PLWH) in Africa ( C112 )
Official scientific title An Experimental Medicine Vaccine Trial of Mosaic HIV-1 Envelope Trimer Immunogens Administered to People Living With HIV PLWH) in Africa, Randomized for Assessment of Fractional Doses
Brief summary describing the background and objectives of the trial According to the Joint United Nations Programme on HIV/AIDS and the World Health Organization, as of the end of 2022, 39 million [33.1 million–45.7 million] people globally were estimated to be living with HIV/AIDS, with 20.8 million people living with HIV in Eastern and Southern Africa in 2022. It is estimated that in 2022 alone, 1.3 million [1 million–1.7 million] people were newly infected with HIV and 630 000 [480 000–880 000] people died from AIDSrelated illnesses in 2022. Although access to antiretroviral treatment has increased, at the end of December 2022, about 29.8 million people (76% [65–89%] of people living with HIV were accessing anti-retroviral treatment [0]. Africa remains the most affected region, with 20.8 million people living with HIV in Eastern and Southern Africa in 2022. For these reasons, it is clear that while antiretroviral therapy is effective, it is not sufficient to end the global AIDS epidemic; ultimately a vaccine would be the most effective option to control and eradicate this infectious disease We are proposing to recruit PLWH on suppressive ART, who will be immunized with mosaic envelope trimer immunogens that were tested in the European AIDS Vaccine Initiative 2020 (EAVI 2020) Phase 1 trial evaluating prime-boost combinations with various forms of HIV-1 SOSIP gp140s adjuvanted with monophosphoryl lipid A (MPLA). The mosaic antigens were generated in silico to cover the global HIV diversity and include common potential B cell epitopes. Our primary goal is to measure the safety of administering a trivalent combination of mosaic envelope trimer immunogens in PLWH. The study will also test a novel immunization strategy based upon fractionated escalating dose delivery of the immunogen over several days compared to traditional bolus dosing. Primary Objective: To evaluate the safety and tolerability of MOS1SIP (Mos3.1) MOS2SIP (Mos3.2) M3SIP8 (Mos3.3) adjuvanted with MPLA when administered in com
Type of trial RCT
Acronym (If the trial has an acronym then please provide) IAVI C112
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Prevention
Anticipated trial start date 01/08/2024
Actual trial start date
Anticipated date of last follow up 31/12/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 40
Actual target sample size (number of participants)
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NCT06449196 ClinicalTrials.gov
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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Bolus Dosing 3 doses 6 months HIV Env Mosaic immunogens MOS1SIP, MOS2SIP, M3SIP8 and Monophosphoryl lipid A liposomes MPLA-5) adjuvant (IM) administered via bolus dosing 20 Active-Treatment of Control Group
Experimental Group Fractionated Dosing 6 smaller amounts 3 weeks (2 visits per week for 3 weeks). The same procedure will be applied at the 2- and 6-month timepoints. HIV Env Mosaic immunogens MOS1SIP, MOS2SIP, M3SIP8 and Monophosphoryl lipid A liposomes (MPLA-5) adjuvant (IM) administered via fractionated dosing 20
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Confirmed HIV-1 infection (HIV Ab+ or HIV RNA+) by documentation in the medical records or in-clinic HIV testing; 2. CD4 ≥ 300 cells/µl; 3. Currently on ART, and documentation of continuous combination ART (cART) treatment with suppression of plasma HIV-1 viral load < 50 copies / ml for greater than 6 months, measured on at least 2 independent occasions, and with a viral load < 50 copies / ml at time of screening (within 42 days prior to IP administration). cART is defined as a regimen including ≥ 2 compounds, e.g., 2 nucleoside reverse transcriptase inhibitors plus either nonnucleoside reverse transcriptase inhibitor or protease inhibitor or integrase inhibitor. 4. Having serum neutralization breadth of at least 20% using a 12-virus global panel at screening. 5. At least 18 years of age on the day of screening and has not reached his or her 51st birthday on the day of signing the Informed Consent Document. 6. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. 7. In the opinion of the Principal Investigator or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential impact and/or risks linked to administration of the investigational product; written informed consent will be obtained from the participant before any study-related procedures are performed. 8. All sexually active female participants capable of becoming pregnant must commit to use an effective method of contraception for 4 months following IP administration, including: a. Condoms (male or female) with or without spermicide b. Diaphragm or cervical cap with spermicide c. Intrauterine device, or contraceptive implant d. Hormonal contraception e. Successful vasectomy in the male partner (considered successful if a woman reports that a male partner has [1] documentation of azoospermia by microscopy (< 1 year ago), or [2] a vasectomy more than 2 years ago 1. Any clinically significant acute or chronic medical condition, other than HIV infection, that is considered progressive or in the opinion of the investigator makes the participant unsuitable for participation in the study. 2. History of AIDS-defining illness or CD4 < 200 cells/µl. 3. If female, pregnant, lactating or planning a pregnancy during the period of screening through completion of the study. 4. In the past 6 months a history of alcohol or substance use, judged by the Investigator to potentially interfere with participant study compliance. 5. Bleeding disorder that was diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions). Note: A participant who states that he or she has easy bruising or bleeding but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience, is eligible. 6. History of a splenectomy. 7. Receipt of live attenuated vaccine within the previous 60 days or planned receipt within 60 days after administration of IP; or receipt of other vaccine within the previous 14 days or planned receipt within 14 days of administration of the IP (exception is live attenuated influenza vaccine within 14 days). 8. Receipt of blood transfusion or blood-derived products within the previous 3 months. 9. Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study. 10. Prior receipt of an investigational HIV vaccine candidate, monoclonal antibody, or polyclonal immunoglobulin (note: receipt of placebo in a previous HIV vaccine or monoclonal antibody trial will not exclude a participant from participation if documentation is available and the Medical Monitor gives approval. 11. History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulties, angioedema); Adult: 18 Year(s)-44 Year(s) 18 Year(s) 50 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 13/05/2024 University of Zambia Biomedical Research Ethics Commiittee
Ethics Committee Address
Street address City Postal code Country
Ridgeway campus Lusaka 50110 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
No 03/07/2024 Rwanda National Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Kigali, Rwanda Kigali 84 Rwanda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To evaluate incidence of reactogenicity events, adverse events and serious adverse events (Safety and Tolerability). Proportion of volunteers with moderate or greater reactogenicity events from initial administration through 7 days following completion of each dose of the investigational product. Proportion of volunteers with moderate or greater vaccine-related unsolicited adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, from initial administration through 28 days following completion of each dose of the investigational product. Proportion of volunteers with vaccine-related serious adverse events (SAEs) throughout the study period. [Time Frame: 15 months] Reactogenicity - 7 days following IP administration. Adverse Events - 28 days following completion of each dose of the investigational product. SAEs - 15 months - throughout the study period.
Secondary Outcome Immunogenicity Proportion of volunteers with improvement in neutralizing activity, based on breadth and potency, prior to and after immunization with the Env Mosaic immunogens. Difference in neutralization breadth and potency with fractionated dosing compared to bolus doses of the Env Mosaic immunogens. Proportion, magnitude, and epitope-specificity of serum IgG binding responses to the Mosaic Env trimers after immunization with the Env Mosaic immunogens compared to baseline. [Time Frame: 15 months] 15 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Center For Family Health Research in Zambia Lusaka, Zambia Post Net 412 P/BagE891 Lusaka E891 Zambia
Center for Family Health Research KK19 AV 57 P.O. Box 780 Kigali 250 Rwanda
FUNDING SOURCES
Name of source Street address City Postal code Country
USAID Washington Washington 20004 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor International AIDS Vaccine Initiative 125 Broad Street, 9th Floor, New York New York 10004 United States of America Not for-Profit Organization
COLLABORATORS
Name Street address City Postal code Country
Polymun Scientific GmbH 99, 3400 Klosterneuburg Austria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator William Kilembe wkilembe@rzhrg-mail.org +260966862787 Center For Family Health Research in Zambia, Lusaka, Zambia, Post Net 412 PBagE891
City Postal code Country Position/Affiliation
Lusaka PBagE891 Zambia Center For Family Health Research in Zambia
Role Name Email Phone Street address
Scientific Enquiries Lebohang Molife LMolife@iavi.org +27768667282 Johannesburg
City Postal code Country Position/Affiliation
Johannesburg South Africa IAVI Africa
Role Name Email Phone Street address
Public Enquiries Vincent Muturi Kioi VMuturi-Kioi@iavi.org +254719043151 The Address, 11th Floor, Waiyaki way
City Postal code Country Position/Affiliation
Nairobi Kenya IAVI Africa
Role Name Email Phone Street address
Principal Investigator Julien Nyombayire JNyombayire@rzhrg-mail.org 250788445504 KK 19 AV 57
City Postal code Country Position/Affiliation
Kigali 780 Rwanda Center for Family Health Research Kigali Rwanda
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The full data package will be made available to the public approximately 12 months after the Study/trial Completion. To protect participant privacy the data package will be sent to a company who specializes in anonymization and pseudonymization of clinical trial data that will strip out or anonymize any potential identifying information such as participant IDs, dates of birth, initials, visit dates, or any other data that alone or in aggregate could identify an individual. Study Protocol Once the final anonymized data package is available it will be posted in a public data repository platform, who will make data available for researchers for 5 years, unless they are contractually unable to do so. The public data repository platform utilizes an independent peer review process to evaluate the validity of external requests. Criteria include the intended analysis by the requestors, professional credentials of the requestors, and the feasibility of the proposed work based on the data requested. After approval by the peer review board, the requestors must sign a data transfer agreement before the data are provided. The data transfer agreement will require the requestor to specify how the transferred data will be held in secure, controlled access during the analysis interval.
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