Trial Outcomes & Findings for Single or Repeat Dose of G03-52-01 in Adult Subjects (NCT NCT05348993)

A total of 622 participants were enrolled into this trial in the United States between June 2022 and February 2025.

The total duration of this trial was up to approximately 254 days for cohorts 1-3 and up to approximately 134 days for cohort 4. The screening period was up to 14 days for all cohorts, and the treatment/follow-up period was 240 days for cohorts 1-3 and 120 days for cohort 4.

Single or Repeat Dose of G03-52-01 in Adult Subjects

An AE was any unfavourable and unintended sign, symptom, or disease temporarily associated with the use of investigational product (IP), whether or not related to the IP. A SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a congenital abnormality/birth defect, or caused any persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Clinically significant changes in physical examination, vital signs, and clinical safety laboratory values were included as AEs.

Pharmacodynamic (PD) samples were tested using the Battelle Mouse Neutralization Assay (MNA) for serotypes A and B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans.

PD samples were tested using the MNA for serotypes A and B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans.

PD samples were tested using the MNA for serotypes A and B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. If pre-dose concentration was inconclusive, not tested, or missing, or if there were fewer than two measurable concentrations in the participant's profile, the parameters were not determined and the participant was excluded from MNA analysis. In the calculation of PD parameters, below limit of quantitation (BLQ) values were treated as zero prior to the first measurable concentration. After the first measurable concentration, subsequent BLQ values were treated as missing. Values that were above the upper limit of quantitation were set to the ULQ (upper limit of quantitation) of the assay for analysis.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. t1/2 was determined after the first dose on Day 1. This value was calculated as t1/2 = ln(2)/ λz where λz is the elimination rate constant. Only samples up to Day 45 predose were used in these calculations, however the above equation allows a half life greater than the sampling interval.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. If pre-dose concentration was inconclusive, not tested, or missing, or if there were fewer than two measurable concentrations in the participant's profile, the parameters were not determined and the participant was excluded from MNA analysis. In the calculation of PD parameters, BLQ values were treated as zero prior to the first measurable concentration. After the first measurable concentration, subsequent BLQ values were treated as missing. Values that were above the upper limit of quantitation were set to the upper limit of quantitation of the assay for analysis.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. If pre-dose concentration was inconclusive, not tested, or missing, or if there were fewer than two measurable concentrations in the participant's profile, the parameters were not determined and the participant was excluded from MNA analysis. In the calculation of PD parameters, BLQ values were treated as zero prior to the first measurable concentration. After the first measurable concentration, subsequent BLQ values were treated as missing. Values that were above the upper limit of quantitation were set to the upper limit of quantitation of the assay for analysis.

The presence of ADA was determined using a validated electrochemiluminescence assay (ECLA) that measured total ADA in serum. Detected and Not Detected results correspond to samples that were potential positive during screening testing. No Recorded Result (NRR) results correspond to samples that were NRR during screening testing. Percentages are based on n, the number of participants in each treatment group with a non-missing result at each time point for the given analyte.

PD samples were tested using the MNA for serotypes A and B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans.

PK parameters were measured by enzyme-linked immunosorbent assay (ELISA) or ECLA for each of the monoclonal antibodies (mAb) of G03-52-01, and PK parameters were estimated for each of the six mAbs separately using noncompartmental methods in WinNonlin or a similar software package.

PK parameters were measured by ELISA or ECLA for each of the mAb of G03-52-01, and PK parameters were estimated for each of the six mAbs separately using noncompartmental methods in WinNonlin or a similar software package.

PK parameters were measured by ELISA or ECLA for each of the monoclonal antibodies (mAb) of G03-52-01, and PK parameters were estimated for each of the six mAbs separately using noncompartmental methods in WinNonlin or a similar software package.

PK parameters were measured by ELISA or ECLA for each of the mAb of G03-52-01, and PK parameters were estimated for each of the six mAbs separately using noncompartmental methods in WinNonlin or a similar software package.

PK parameters were measured by ELISA or ECLA for each of the monoclonal antibodies (mAb) of G03-52-01, and PK parameters were estimated for each of the six mAbs separately using noncompartmental methods in WinNonlin or a similar software package.

PK parameters were measured by ELISA or ECLA for each of the mAb of G03-52-01, and PK parameters were estimated for each of the six mAbs separately using noncompartmental methods in WinNonlin or a similar software package.

PK parameters were measured by ELISA or ECLA for each of the mAb of G03-52-01, and PK parameters were estimated for each of the six mAbs separately using noncompartmental methods in WinNonlin or a similar software package.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. If pre-dose concentration was inconclusive, not tested, or missing, or if there were fewer than two measurable concentrations in the participant's profile, the parameters were not determined and the participant was excluded from MNA analysis. In the calculation of PD parameters, BLQ values were treated as zero prior to the first measurable concentration. After the first measurable concentration, subsequent BLQ values were treated as missing. Values that were above the upper limit of quantitation were set to the upper limit of quantitation of the assay for analysis.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. t1/2 was determined after the first dose on Day 1. This value was calculated as t1/2 = ln(2)/ λz where λz is the elimination rate constant. Only samples up to Day 45 were used in these calculations, however the above equation allows a half life greater than the sampling interval.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. If pre-dose concentration was inconclusive, not tested, or missing, or if there were fewer than two measurable concentrations in the participant's profile, the parameters were not determined and the participant was excluded from MNA analysis. In the calculation of PD parameters, BLQ values were treated as zero prior to the first measurable concentration. After the first measurable concentration, subsequent BLQ values were treated as missing. Values that were above the upper limit of quantitation were set to the upper limit of quantitation of the assay for analysis.

PD samples were tested by MNA for serotypes BoNT/A and BoNT/B. The MNA was used to determine the concentration of functional antibodies in a sample capable of neutralizing BoNT (i.e., amount of BoNT/A or BoNT/B toxin neutralization afforded by the combination of antibodies). NAC, as measured by the MNA, is proposed to bridge efficacy between animal models and humans. If pre-dose concentration was inconclusive, not tested, or missing, or if there were fewer than two measurable concentrations in the participant's profile, the parameters were not determined and the participant was excluded from MNA analysis. In the calculation of PD parameters, BLQ values were treated as zero prior to the first measurable concentration. After the first measurable concentration, subsequent BLQ values were treated as missing. Values that were above the upper limit of quantitation were set to the upper limit of quantitation of the assay for analysis.

The presence of ADA was determined using a validated ECLA that measured total ADA in serum. Detected and Not Detected results correspond to samples that were potential positive during screening testing. NRR results correspond to samples that were NRR during screening testing. Percentages are based on n, the number of participants in each treatment group with a non-missing result at each time point for the given analyte.