Overview

PedMAb1 is a sequential and randomized, phase I, single-site, single-blind, dose-finding, trial investigating the safety and PK profile of incrementally higher broadly neutralizing antibodies, (bNAbs), VRC07-523LS and CAP256V2LS, doses in breastfeeding HEU neonates also treated with the standard-of-care antiretroviral (ARV) prophylaxis.

It is composed of 3 steps and has 9 arms. Randomization will occur sequentially and will occur between Arms (i) 2 & 4, (ii) 3 & 5, (iii) 6 & 7 and (iv) 8 & 9.

Before each randomization starts there will be a safety pause to review safety data of the current arms before moving to the next randomization. We aim to recruit about 72 babies.

The 3 steps are summarized below.

Primary Objectives

To evaluate the safety (Adverse Events = AE) until day 28 after a single subcutaneous (SC) administration of one bNAb, tested at increasing doses within 72 hours of birth, in breastfeeding HEU neonates (arms 1 through 5).
To evaluate the safety (adverse events) until day 28 after two single SC administration of two bNAbs, tested at increasing doses within 72 hours of birth, in breastfeeding HEU neonates (arms 6 and 7).
To evaluate the safety (adverse events) until day 28 after two single SC administrations of two bNAbs, within 72 hours of birth and repeated at 2 months (arms 6b and 7b) or at a time point between 3 and 6 months (arms 8 and 9) (to be defined according to PK data (from analysis of the previous arms) in breastfeeding HEU neonates.

Primary endpoint

The primary endpoint, applying to all the primary objectives, is the proportion of participants who develop at least one ≥ Grade 3 AE, including local and systemic reactions, lab toxicities, and/or clinical events, that is possibly, probably or definitely related to each bNAb any time from the first day of study product administration through further 28 days following bNAb(s) administration (all arms).

Where is the study being conducted?

The study is being conducted in South Africa only. It is conducted at the SAMRC (South African Medical Research Council), HIDRU (HIV and other Infectious Diseases Research Unit) - Chatsworth Clinic Research Site (CRS) which is located on the grounds of the RK Khan Hospital, eThekwini district, KwaZulu-Natal

RK Khan Hospital entrance

Chatsworth CRS location

Chatsworth CRS PedMAb1 prefab

Waiting area

Entrance to & Inside the prefab

Observation & Counselling rooms

Eligibility: Who can enrol?

PedMAb1 Inclusion and Exclusion Criteria: Mother

Inclusion

Exclusion

Greater than or equal to 18 years of age
Documented HIV-1 infection
Breastfeeding at the time of consenting or willing to initiate breastfeeding in the immediate post partum period.
Able and willing to provide a signed informed consent form to participate in the study for herself and her infant.

Prior participation in any HIV-1 vaccine trial
Receipt of any other active or passive HIV immunotherapy or investigational product concurrently
Documented or suspected serious medical illness with fetal compromise or immediate life-threatening condition (other than HIV-infection as judged by the examining clinician)
Most recent CD4 count (within a time frame of ≤6 months) under 350 cells/mm3
Mother not on ART
Unable or not willing to breastfeed
Active tuberculosis
COVID-19 diagnosis in the past month
Plan to relocate in 1 year
Mother does not have her own cell phone
Mother not able to provide three alternate contact phone numbers

PedMAb1 Inclusion and Exclusion Criteria: Infant

Inclusion

Exclusion

Alive infant with a birth weight greater than or equal to 2.0 kg and lower than or equal to 4.0kg
Gestational age greater or equal to 36 weeks, assessed using birth Ballard Score (done up to 42 hours after birth)
Written consent of the one or both parents (according to South African regulation)

HIV-infected on birth PCR
Receipt of or anticipated need for blood product, immunoglobulin or immunosuppressive therapy. This includes infants who require hepatitis B immunoglobulins (HBIG) but not infants who receive hepatitis B vaccine in the new-born period
Documented or suspected serious medical or immediate life-threatening condition
Infant in ICU or high care requiring supplemental oxygen at time of first bNAb dose
Known allergy to study drug or components
Multiple birth, i.e. twins, triplets, quadruplets, etc
Baseline laboratory results:
Haemoglobin level less than 12.0 g/dL
Platelet count less than 100,000 cells/mm3
Absolute neutrophil count: for infants less than 24 hours old, less than 4,000 cells/mm3; for infants greater than 24 hours old, less than 1,250 cells/mm3
Serum glutamic pyruvic transaminase (SGPT), alanine aminotransferase (ALT) greater than or equal to 1.25 times upper limit of age-adjusted normal.
Serum bilirubin at a level needing phototherapy

PedMAb1

Overview

Primary Objectives

Primary endpoint

Where is the study being conducted?

Eligibility: Who can enrol?

PedMAb1 Inclusion and Exclusion Criteria: Mother

Inclusion

Exclusion

PedMAb1 Inclusion and Exclusion Criteria: Infant

Inclusion

Exclusion

Acknowledgement

Links

Contact Details