Ignite Creation Date:
2024-05-06 @ 7:18 PM
Last Modification Date:
2024-10-26 @ 3:04 PM
Study NCT ID:
NCT05969977
Status:
RECRUITING
Last Update Posted:
2023-08-01
First Post:
2023-06-11
Brief Title:
A First-in-Human Phase 1 Study of Plasmalogen Precursor PPI-1011 in Healthy Adult Volunteers to Assess Safety Tolerability and Pharmacokinetics
Sponsor:
MED-LIFE DISCOVERIES LP
Organization:
MED-LIFE DISCOVERIES LP
Study Overview
Official Title:
A Phase 1 Randomized Double-blind Placebo-controlled Combined Single and Multiple Ascending Dose Study of PPI-1011 in Subjects to Assess Safety Tolerability and Pharmacokinetics
Status:
RECRUITING
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
PPI-1011 is being developed as a docosahexaenoic acid DHA containing plasmalogen precursor with good long-term stability specifically for the treatment of rhizomelic chondrodysplasia punctata RCDP which is an ultra rare type of peroxisomal biogenesis disorder PBD The goal of treatment with PPI-1011 is to increase the levels of plasmalogens within circulation and tissues with the hope that this will normalize plasmalogen levels in the body and result in clinical improvement to patients The present study is a first-in-human FIH phase 1 randomized double-blind placebo-controlled dose-escalation study to assess the safety tolerability and pharmacokinetics PK of single and multiple ascending doses of PPI-1011 administered orally to healthy subjects The study consists of 5 planned single-dose cohorts n 8 per cohort total randomized 6 active 2 placebo with sentinel design Following a review of the safety and PK data by the safety review committee and submission to Health Canada the study will be expanded to include 2 planned multiple-dose cohorts n 8 per cohort total randomized 6 active 2 placebo
Detailed Description:
This is a randomized double-blind placebo-controlled first-in-human FIH study of PPI-1011 in healthy male and non-pregnant non-lactating female volunteers The study will consist of two parts single ascending dose SAD and multiple ascending dose MAD The study will evaluate the safety tolerability and PK in 5 planned SAD cohorts with sentinel design n8 per cohort total randomized 6 active 2 placebo and 2 planned MAD cohorts n8 per cohort total randomized 6 active 2 placebo Based on accumulating data additional single-dose andor a multiple-dose cohorts n8 per cohort may be added to better assess the safety tolerability or PK profile of PPI-1011 to meet study objectives and try to determine the maximum tolerated dose
A sentinel dose in 2 participants 11 PPI-1011 placebo will be performed in each single-dose cohort to evaluate the safety and tolerability at planned doses Additional cohorts will be dosed in case a different doses is required based upon the emerging safety and PK data from the main cohorts to provide better assessment for the safety tolerability or PK of PPI-1011 A sentinel design may not be applicable when a cohort with the same or a higher drug exposure has already been evaluated
Single Ascending Dose SAD
The 5 planned single-dose levels are
Cohort A 10 mgkg PPI-1011 or Placebo Cohort B 25 mgkg PPI-1011 or Placebo Cohort C 50 mgkg PPI-1011 or Placebo Cohort D 75 mgkg PPI-1011 or Placebo Cohort E 100 mgkg PPI-1011 or Placebo
Dose levels may be changed andor additional cohorts may be added based on emerging safety and PK data Subjects enrolled in the single-dose treatment cohorts will receive a single dose of the study drug PPI-1011 or placebo orally on Day 1
A period of at least 24 hours will be required between administering study drug to the first 2 subjects 1 active 1 placebo and the 6 remaining subjects 5 active 1 placebo in the cohort If no major safety concerns are observed following 24 hours of observation dosing of the remaining 6 participants in that cohort may proceed The dose-escalation may proceed after the Safety Review Committee review of the blinded safety data up to at least Day 3 from all participants in the preceding single-dose cohort The dose escalation decision will be based on safety evaluation for an acceptable safety profile as determined by the SRC
Cohorts A B C D and E will be dosed in a non-fasting state
Multiple Ascending Dose MAD
The 2 planned multiple-dose levels are
Cohort AA
Study Drug Dose TBD mgkg PPI-1011 or Placebo Dosing Regimen 1 x TBD mgkg every 24 hours Duration Days 14 Total Dose mgkg TBD
Cohort BB
Study Drug Dose TBD mgkg PPI-1011 or Placebo Dosing Regimen 1 x TBD mgkg every 24 hours Duration Days 14 Total Dose mgkg TBD
Cohorts AA and BB will be dosed in a non-fasting state
MAD dosing levels will be decided after review of the safety and PK data from the SAD cohorts The SRC will propose doses which will be submitted to Health Canada together with the safety and PK data from the SAD Dose levels may be further adjusted based on emerging safety and PK data from MAD cohorts
Subjects enrolled in the multiple-dose treatment cohorts will receive oral doses of the study drug PPI-1011 or placebo once daily at 24-hour intervals Thus the total number of doses subjects will receive in a MAD cohort will be up to 14 doses The doses for these cohorts will be selected after review of the blinded safety and PK data by the SRC and submitted to Health Canada The dose in the MAD will not exceed the doses tested in the SAD
Treatment Phases
Single-Dose Cohorts In-Clinic
Participants will check in on Day -1 On Day 1 participants will receive a single dose of PPI-1011 or placebo Participants will remain confined in the clinic from Day -1 until Day 2 at least 36 hours after dosing Participant can stay longer in the clinic if deemed necessary upon the Investigators discretion
Single-Dose Cohorts Outpatient Visits
After completing the in-house confinement period participants will return to the clinic for an outpatient visit on Day 3 Day 4 Day 5 and Day 6
Multiple-Dose Cohorts In-Clinic
Participants will check in on Day -1 Participants will receive oral doses of PPI-1011 or placebo from Day 1 to Day 14 Participants will remain confined in the clinic from Day -1 through Day 15 at least 36 hours after the last dose Participant can stay longer in the clinic if deemed necessary upon the Investigators discretion
Multiple-Dose Cohorts Outpatient Visits
After completing the confinement period participants will return to the clinic for an outpatient visit on Day 16 Day 17 Day 18 and Day 19
Study Numbers
Fifty-six 56 healthy volunteers are planned to be enrolled in this study Forty 40 subjects will be enrolled in the SAD portion of the study and 16 subjects will be enrolled in the MAD portion n8 per cohort For SAD cohorts each cohort will enroll a minimum of 3 subjects of each sex with at least 2 males and 2 females randomized to the active treatment The same may be implemented for MAD cohorts based on emerging safety and PK data
Additional subjects in single n8 or multiple dose n8 cohorts may be added to better assess the safety tolerability or PK of PPI-1011 to meet study objectives
A sentinel dose in 2 participants 11 PPI-1011 placebo will be performed in each single-dose cohort to evaluate the safety and tolerability at planned doses Additional cohorts will be dosed in case a different doses is required based upon the emerging safety and PK data from the main cohorts to provide better assessment for the safety tolerability or PK of PPI-1011 A sentinel design may not be applicable when a cohort with the same or a higher drug exposure has already been evaluated
Single Ascending Dose SAD
The 5 planned single-dose levels are
Cohort A 10 mgkg PPI-1011 or Placebo Cohort B 25 mgkg PPI-1011 or Placebo Cohort C 50 mgkg PPI-1011 or Placebo Cohort D 75 mgkg PPI-1011 or Placebo Cohort E 100 mgkg PPI-1011 or Placebo
Dose levels may be changed andor additional cohorts may be added based on emerging safety and PK data Subjects enrolled in the single-dose treatment cohorts will receive a single dose of the study drug PPI-1011 or placebo orally on Day 1
A period of at least 24 hours will be required between administering study drug to the first 2 subjects 1 active 1 placebo and the 6 remaining subjects 5 active 1 placebo in the cohort If no major safety concerns are observed following 24 hours of observation dosing of the remaining 6 participants in that cohort may proceed The dose-escalation may proceed after the Safety Review Committee review of the blinded safety data up to at least Day 3 from all participants in the preceding single-dose cohort The dose escalation decision will be based on safety evaluation for an acceptable safety profile as determined by the SRC
Cohorts A B C D and E will be dosed in a non-fasting state
Multiple Ascending Dose MAD
The 2 planned multiple-dose levels are
Cohort AA
Study Drug Dose TBD mgkg PPI-1011 or Placebo Dosing Regimen 1 x TBD mgkg every 24 hours Duration Days 14 Total Dose mgkg TBD
Cohort BB
Study Drug Dose TBD mgkg PPI-1011 or Placebo Dosing Regimen 1 x TBD mgkg every 24 hours Duration Days 14 Total Dose mgkg TBD
Cohorts AA and BB will be dosed in a non-fasting state
MAD dosing levels will be decided after review of the safety and PK data from the SAD cohorts The SRC will propose doses which will be submitted to Health Canada together with the safety and PK data from the SAD Dose levels may be further adjusted based on emerging safety and PK data from MAD cohorts
Subjects enrolled in the multiple-dose treatment cohorts will receive oral doses of the study drug PPI-1011 or placebo once daily at 24-hour intervals Thus the total number of doses subjects will receive in a MAD cohort will be up to 14 doses The doses for these cohorts will be selected after review of the blinded safety and PK data by the SRC and submitted to Health Canada The dose in the MAD will not exceed the doses tested in the SAD
Treatment Phases
Single-Dose Cohorts In-Clinic
Participants will check in on Day -1 On Day 1 participants will receive a single dose of PPI-1011 or placebo Participants will remain confined in the clinic from Day -1 until Day 2 at least 36 hours after dosing Participant can stay longer in the clinic if deemed necessary upon the Investigators discretion
Single-Dose Cohorts Outpatient Visits
After completing the in-house confinement period participants will return to the clinic for an outpatient visit on Day 3 Day 4 Day 5 and Day 6
Multiple-Dose Cohorts In-Clinic
Participants will check in on Day -1 Participants will receive oral doses of PPI-1011 or placebo from Day 1 to Day 14 Participants will remain confined in the clinic from Day -1 through Day 15 at least 36 hours after the last dose Participant can stay longer in the clinic if deemed necessary upon the Investigators discretion
Multiple-Dose Cohorts Outpatient Visits
After completing the confinement period participants will return to the clinic for an outpatient visit on Day 16 Day 17 Day 18 and Day 19
Study Numbers
Fifty-six 56 healthy volunteers are planned to be enrolled in this study Forty 40 subjects will be enrolled in the SAD portion of the study and 16 subjects will be enrolled in the MAD portion n8 per cohort For SAD cohorts each cohort will enroll a minimum of 3 subjects of each sex with at least 2 males and 2 females randomized to the active treatment The same may be implemented for MAD cohorts based on emerging safety and PK data
Additional subjects in single n8 or multiple dose n8 cohorts may be added to better assess the safety tolerability or PK of PPI-1011 to meet study objectives
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None