A Phase IIa Open-Label, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD)
Study ID: STU 052016-071
This Phase iia study is an open-label, multiple ascending dose study to evaluate the safety, tolerability, PK, PD, and exploratory clinical efficacy of oral vamorolone over the course of a 14-day Treatment Period in ambulant boys ages 4-[Less Than] 7 years with DMD. The study is comprised of a 26-day Pretreatment Screening Period, a 1-day Pretreatment Baseline Period, a 14-day Treatment Period, and a 14-day Post-treatment Follow-up Period. note: Subjects who complete the 14-day Follow-up Period will be given the option of continuing vamorolone treatment in an extension study under a separate protocol (VBP15-003). For each dose, at least 3 subjects will be enrolled (unless there are dose limiting toxicities in the first 2 subjects) in order to have minimum data for the dose level. after the first 3 subjects in each dose level group have completed the 2-week Treatment Period, the toxicity probability interval (TPi) will be calculated to determine whether to escalate to the next dose, stay at the current dose, or de-escalate to a lower dose. This process will be repeated after each subject following the third subject in the dose level group has completed the 2-week Treatment Period. if Dose Level Group 3 is reached and the TPi does not recommend de-escalating, the dose level group will be filled to the maximum of 12 subjects before or after escalating to Dose Level Group 4, if appropriate by TPi. if Dose Level Group 4 is reached and at no time does the TPi recommend to de-escalate, Dose Level Group 4 will also recruit to the maximum of 12 subjects. if Dose Level Group 3 is reached and the TPi recommends de-escalating, Dose Level Groups 1 and 2 will each be filled to the maximum of 12 subjects, if appropriate by the TPi. if Dose Level Group 4 is reached and the TPi recommends de-escalating, Dose Level Groups 2 and 3 will each be filled to the maximum of 12 subjects, if appropriate by the TPi. if a de-escalation occurs, a dose level may still be a candidate for future escalation back to that dose, depending on future subjects' results, or may be considered to have unacceptable toxicity if a threshold is crossed and no longer considered, based on the TPi. Thus, this design maintains the safety of the subjects by not escalating unless the TPi suggests escalating to the next higher dose, but also expands latter dose level groups to have sufficient numbers for overall estimates of safety, PK, PD and baseline assessments of preliminary efficacy outcomes to be followed via an extension study (VBP15-003).
1. Subject[Single Quote]s parent or legal guardian has provided written informed consent/Health Insurance Portability and Accountability Act (HIPAA) 2. Subject has a confirmed (by Central Genetic Counselor) diagnosis of DMD as defined as: a) Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR b) Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame', and clinical picture consistent with typical DMD, OR c) Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e. nonsense mutation, deletion/duplication leading to a downstream stop codon), with a typical clinical picture of DMD 3. Subject is >= 4 years and < 7 years of age at time of enrollment in the study 4. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance, as assessed at the Screening or and Baseline Visits 5. Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant, in the opinion of the Investigator. (Note: Serum gamma glutamyl transferase [GGT], creatinine, and total bilirubin all must be <= upper limit of the normal range at the Screening Visit) 6. Subject has evidence of chicken pox immunity as determined by prior vaccination or presence of IgG antibodies to varicella, as documented by a positive test result from the testing laboratory at the Screening Visit 7. Subject and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Diana Patricia Castro
ReveraGen BioPharma Inc