HIV Infections
Conditions
Keywords
Cabotegravir, Neonate, HIV, Safety, Tolerability, Pharmacokinetics
Brief summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of cabotegravir in neonates exposed to human immunodeficiency virus (HIV)-1.
Interventions
DRUGOral CAB
CAB administered once orally on study Day 1 to the Stage 1: Single Oral Dose CAB (Cohort 1) and multiple times to the Stage 1: Multiple Oral Dose CAB (Cohort 2) group. Dose and dosing frequency for Cohort 2 to be determined based on emerging data from Cohort 1.
DRUGIM CAB LA
CAB LA administered once intramuscularly on study Day 1 to the Stage 2: Single IM Dose CAB LA (Cohort 3) group and multiple times to the Stage 2: Multiple IM Dose CAB LA (Cohort 4) group, into the in the anterolateral thigh muscle of participants. Dose for Cohort 3 to be determined based on emerging data from Cohort 2. Dose and dosing frequency for Cohort 4 to be determined based on emerging data from Cohort 3.
Sponsors
ViiV Healthcare
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Masking description
Open-label study.
Intervention model description
The study will be conducted in a staggered design. There will be 2 stages with 2 cohorts in each. The 1st stage will focus on the oral CAB, the 2nd on the CAB LA injectable. In the 1st cohort at each stage, a single dose will be given. In the 2nd cohort of each stage, there will be a multi-dose regimen. Dose review decisions will be based upon safety, tolerability and pharmacokinetic data from each cohort.
Eligibility
Sex/Gender
ALL
Age
No minimum to 10 Days
Healthy volunteers
Yes
Inclusion criteria
* At least 37 weeks gestation at delivery. * \<=10 days of life. * Birth weight at least 2 kg. * At Entry, neonate has initiated standard of care Antiretroviral drug (ARV) prophylaxis. * At Entry, neonate is generally healthy as determined by the site Investigator based on review of all available medical history information and physical examination findings. * Mother is on a Dolutegravir (DTG) based regimen for a minimum of 4 weeks prior to delivery, regardless of maternal viral load. * Mother is currently breastfeeding or plans to breastfeed infant. * Mother is of legal age or circumstance to provide independent informed consent and is willing and able to provide documented informed consent for her and her infant's participation in this study. * Mother has confirmed HIV-1 infection based on positive test results from 2 samples collected from 2 separate blood samples. Test results may be obtained from medical records or from testing performed during the study Screening period.
Exclusion criteria
Medical conditions * Severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by examining clinician. * Known maternal-fetal blood group incompatibility which can result in hemolytic disease of the newborn. * Known family history of G6PD deficiency. * Prior/Concomitant therapy * Mother who has previously received, is receiving, or will be receiving CAB post-partum. * Neonate or breastfeeding mother is receiving any disallowed medication. * Prior/Concurrent clinical study participation * Neonate has exposure to other investigational drugs that might interfere with study intervention metabolism. * Diagnostic assessments * Mother has known Integrase strand transfer inhibitor (InSTI) resistance. * At Entry, neonate with a confirmed, documented positive HIV Nucleic acid amplification test (NAAT) test result. * At Screening, neonate has any of the following laboratory test results: * Alanine transaminase or Aspartate aminotransferase of more than 2.5 x Upper limit of normal (ULN). * Total bilirubin in range for phototherapy at Entry. * Hemoglobin \<13.0 g/dL. * Decreased white blood cells Grade 3 or above. * Platelets \<50 000 cells/mm3 * Creatinine value more than 1.3 the ULN for postnatal age as defined in Division of AIDS (DAIDS) * Albumin Grade 3 or higher. * Direct bilirubin Grade 3 and above. * Any other Grade ≥3 event on DAIDS toxicity table * Neonates with prior exchange transfusion. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who discontinue the study intervention due to AEs or injection intolerability | From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. |
| Number of participants with serious AEs (SAEs) by severity | From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group) | An SAE is defined as any untoward medical occurrence that is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in death. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity. |
| Number of participants with injection site reactions (ISRs) by severity | From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group) | An ISR is defined as an adverse event which is localized at the injection site, typically includes pain, tenderness, erythema, redness, induration, swelling, nodules or pruritus, but may also encompass other reactions. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity. |
| Maximum observed plasma concentration (Cmax) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group | At study Days 1, 3, 8, 15 and 22 | Blood samples are collected at specific time points for PK analysis to determine Cmax. |
| Maximum observed plasma concentration (Cmax) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group | At study Days 1, 3, 9,16, 28 and 42 | Blood samples are collected at specific time points for PK analysis to determine Cmax. |
| Last observed plasma concentration (Clast) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group | At study Days 1, 3, 8, 15 and 22 | Blood samples are collected at specific time points for PK analysis to determine Clast. |
| Last observed plasma concentration (Clast) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group | At study Days 1, 3, 9, 16, 28 and 42 | Blood samples are collected at specific time points for PK analysis to determine Clast. |
| Area under the curve time 0 to the last time point (AUC0-t) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group | At study Days 1, 3, 8, 15 and 22 | Blood samples are collected at specific time points for PK analysis to determine AUC0-t. |
| Area under the curve time 0 to the last time point (AUC0-t) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group | At study Days 1, 3, 9, 16, 28 and 42 | Blood samples are collected at specific time points for PK analysis to determine AUC0-t. |
| Pre-dose concentrations (C0h) of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group | At Study Days 1, 3, 7, 14, 28, 35, 42 and 49 | Blood samples are collected at specific time points for PK analysis to determine C0h. |
| Pre-dose concentrations (C0h) of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group | At Study Days 1, 3, 7, 21, 28, 42, 56, 70, 84, 98, 112, 140 and 168 | Blood samples are collected at specific time points for PK analysis to determine C0h. |
| Post-dose concentrations of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group | At Study Days 1, 3, 7, 14, 21, 28, 35, 42 and 49 | Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations. |
| Post-dose concentrations of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group | At Study Days 1, 3, 7, 14, 21, 28, 35, 42, 56, 70, 84, 98, 112, 140 and 168 | Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations. |
| Number of participants with drug-related adverse event (AEs) by severity | From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group) | A drug-related AE is any untoward medical occurrence in a clinical study participant considered related to the study intervention. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Grade 3 and above bilirubin elevation. | From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group) | The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity. |
| Number of participants developing Grade 3 and higher AEs and SAEs, by severity | From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in death. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity. |
Contacts
Primary ContactUS GSK Clinical Trials Call Center
Backup ContactEU GSK Clinical Trials Call Center
Outcome results
None listed