Table 2.

Pausing Rules

Applicable to sentinel cohorts

1. Occurrence of any death

2. Occurrence of any serious adverse event, defined as life threatening, requiring hospitalization, resulting in a persistent or significant disability/incapacity, a congenital anomaly or birth defect in the offspring of a study participant, or a medically important condition that may have jeopardized the subject, and may have required medical or surgical intervention to prevent a serious outcome

3. Occurrence of any case of severe allergic reaction, such as anaphylaxis, generalized urticaria, laryngospasm, or bronchospasm

4. One or more subjects experience a severe (nonserious) adverse event, including local, febrile or systemic reactions

Applicable to post-sentinel cohorts

1. Occurrence of any death

2. Occurrence of any serious adverse event other than the result from trauma or accident, regardless of relatedness to study product

3. Occurrence of any case of severe allergic reaction, such as anaphylaxis, generalized urticaria, laryngospasm, or bronchospasm

4. Two or more subjects recruited up to that point experience a severe (nonserious) adverse event, defined as causing inability to perform usual social and functional activities, including local, febrile, or systemic reactions, considered at least possibly related to the investigational product

5. Three or more subjects recruited up to that point experience a severe (nonserious) adverse event, irrespective of the relationship with the investigational product