Fetal and Neonatal Alloimmune Thrombocytopenia
Conditions
Brief summary
The purpose of this Phase 2 study is to assess the pharmacokinetics (PK) and safety of RLYB212 in HPA-1b/b pregnant women at higher risk for HPA-1a alloimmunization and FNAIT.
Detailed description
This study is a single-arm, open-label, multicenter study of RLYB212 in HPA-1b/b pregnant participants at higher risk for the occurrence of HPA-1a alloimmunization and FNAIT. A laboratory testing paradigm will be applied at screening to identify women at higher risk for HPA-1a alloimmunization. Study IPA2202 is comprised of three phases: a two-part screening phase, an antenatal treatment phase, and a postpartum follow-up phase. Study duration for each participant is anticipated to be \ 44 weeks, inclusive of the screening visits through the Week 10 postpartum visit.
Interventions
DRUGAnti-(integrin beta-3) human monoclonal antibody
human monoclonal anti-human platelet antigen (HPA)-1a immunoglobulin G antibody
Sponsors
Rallybio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
Pregnant women who present at Gestational Week 6 or after and confirmed to be: HPA-1b/b (HPA-1a negative), HLA-DRB3\*01:01 positive, Anti-HPA-1a alloantibody negative, Carrying an HPA-1a/b (HPA-1a positive) fetus
Exclusion criteria
* Prior history of HPA-1a related fetal and neonatal alloimmune thrombocytopenia * Multiple pregnancy (more than 1 fetus) * Prior history of platelet transfusion or other blood transfusions * Known sensitivity and/or immediate hypersensitivity to any components of RLYB212 or its formulation * Any co-morbid medical or obstetric condition(s), laboratory abnormality, concomitant treatment, or other reason that, in the investigator's opinion, could adversely affect the safety of the participant and/or fetus, impair the assessment of study results, or preclude compliance with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Related Adverse Events as Defined by CTCAE 5.0 | Approx. Gestational Week (GW) <16, 16, 18, 20, 24, 26, 28, 30, 32, 34, 36, 38; at birth (~40), Post Partum (PP) Week 4, 10 week | Adverse Events will be collected throughout the study from the time of screening part 2 and beyond until the end of study visit (10 weeks postpartum for the maternal participant and 4-6 weeks of age for the neonate/infant). MedDRA version 27.0 or above will be used to code the AEs. All maternal AEs will be graded according to the National Cancer Institute of Common Terminology Criteria for AEs (CTCAE version 5.0 or higher) and Maternal and Fetal Adverse Event Terminology (MFAET version 1.0 or higher). |
| Maternal Exposure to RLYB212 as Measured in Serum | Approx. GW 16, 18, 20, 24, 26, 28, 30, 32, 34, 36, 38, at birth (~40), PP Week 4 | The PK profile of RLYB212 during pregnancy following repeat SC administration was evaluated. Results reported in concentration only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neonatal Exposure to RLYB212 as Measured in Cord Blood | At birth (~GW 40) | The neonatal exposure to RLYB212 was to be measured by sampling and measuring the concentration of RLYB212 in a cord blood sample. |
| Number of HPA-1a Positive Neonates With Treatment Related Adverse Events as Defined by CTCAE v5.0 | At birth (~GW 40), Approx. PP Week 4 | The safety of RLYB212 in the HPA-1a positive neonate would be assessed by treatment related adverse events as defined by CTCAE v5.0 |
| Pregnancy Outcomes: Incidence of Live Births, Spontaneous Abortions, Elective Abortions, Still Births or Premature Births | At birth (~GW 40) | The pregnancy and neonatal outcomes following antenatal RLYB212 administration was assessed by reporting incidence of live births, spontaneous abortions, elective abortions, still births or premature births. |
| Frequency of Neonatal Thrombocytopenia as Measured by Platelet Count Within 72 Hours of Delivery | At birth (~GW 40) | The occurrence of neonatal thrombocytopenia following antenatal RLYB212 administration was assessed. |
| Frequency of HPA-1a Alloimmunization as Measured by Anti-HPA-1a Alloantibodies | Approx. PP Week 10 | The occurrence of HPA-1a alloimmunization was to be assessed by looking for anti-HPA-1a alloantibodies in the woman's blood. |
| Neonatal Outcomes: General Health and Overall Status as Defined by Absolute Values and Percentiles | 4-6 weeks following delivery | Neonate general health measured by Body Length (for age percentile) , Head Circumference (for age percentile), Weight for Height Percentile (for age percentile) |
| Participants That Test Positive for Anti-RLYB212 Antibodies as Measured in Their Serum | 16, 20, 24, 28, 32, 36, at birth (~40), PP Week 4 | Participants that test positive for Anti-RLYB212 antibodies as measured in their serum. The immunogenicity of RLYB212 was assessed by testing serum samples for absence or presence of ADAs. The detection and characterization of ADA against RLYB212 will be performed using a validated assay method by or under the supervision of the Sponsor. The titer of confirmed positive samples will be reported as well as the presence of neutralizing antibodies. Other analyses may be performed to verify the stability of antibodies to RLYB212, and/or further characterize the immunogenicity of RLYB212. |
Countries
Netherlands, Norway, Sweden
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
None listed