A First-in-Human Phase 1 Study of Plasmalogen Precursor PPI-1011 in Healthy Adult Volunteers to Assess Safety, Tolerability, and Pharmacokinetics

NCT05969977 | Unknown Phase 1 DMC

• 1 other identifier: MLD-CT-1.1
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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).

Conditions

Rhizomelic Chondrodysplasia Punctata

Keywords

Phase 1; Healthy Adult Volunteer; RCDP; Plasmalogen; Rhizomelic Chondrodysplasia Punctata

Outcome Measures

Primary Outcomes (1)

• Treatment-emergent adverse events as assessed by the CTCAE scale

  Emergence of adverse events will be documented for incidence, severity and duration and rated according to the CTCAE criteria.

  Up to 6 days post-dose in single ascending dose subjects and up to 7 days post the last dose in multiple ascending dose subjects.

Secondary Outcomes (8)

• Pharmacokinetics-AUC

  Up to 6 days post-dose in single ascending dose subjects and up to 7 days post the last dose in multiple ascending dose subjects.

• Pharmacokinetics-Cmax

  Up to 6 days post-dose in single ascending dose subjects and up to 7 days post the last dose in multiple ascending dose subjects.

• Pharmacokinetics-Tmax

  Up to 6 days post-dose in single ascending dose subjects and up to 7 days post the last dose in multiple ascending dose subjects.

• Pharmacokinetics-T1/2

  Up to 6 days post-dose in single ascending dose subjects and up to 7 days post the last dose in multiple ascending dose subjects.

• Pharmacokinetics-λ

  Up to 6 days post-dose in single ascending dose subjects and up to 7 days post the lst dose in multiple ascending dose subjects.

Study Arms (2)

PPI-1011

EXPERIMENTAL

Single Ascending: PPI-1011 at 10, 25, 50, 75 and 100 mg/kg. Multiple Dose: PPI-1011 dose to be based on SAD; duration 14 days; one dose daily.

Drug: PPI-1011

Placebo

PLACEBO COMPARATOR

Placebo arm.

Drug: Placebo

Interventions

PPI-1011 DRUG

PPI-1011 is a liquid oil with light yellow to amber color, clear to slightly opalescent and flows readily at room temperature. It is insoluble in water and miscible with dichloromethane and liquid coconut oil. It is a synthetic glycerolipid derivative, comprised of an assembly of naturally-occurring products including glycerol backbone, an ether-linked hexadecyl group at sn1 position, an all-cis-4, 7, 10, 13, 16, 19-docosahexaenoyl group at sn2 position, and a lipoyl group at sn3 position. It was designed as a plasmalogen precursor and is similar in structure to naturally occurring alkyl-diacyl lipids with the primary difference being the presence of a lipoic acid moiety at the sn3 position. PPI-1011 is formulated in liquid coconut oil containing 0.1% 1-thioglycerol as an antioxidant.

PPI-1011

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, non-smoking (for at least 6 months prior to first study drug administration) male, and non-pregnant and non-lactating female (including post-menopausal and surgically sterile female) volunteers, 18-65 years of age, inclusive at the time of informed consent.
• Post-menopausal for at least 1 year \[confirmed by FSH (16-157 IU/L) and 17β-estradiol (\<202 pmol/L) levels\]
• Surgically sterile (Partial or total hysterectomy, bilateral oophorectomy, bilateral salpingo-oophorectomy) for at least 6 months \[confirmed by medical/operative report or if medical/operative report is not available by FSH and 17β-estradiol tests, if applicable\].
• Body mass index (BMI) that is within 18.5 - 30.0 kg/m2, inclusive, and subject weighs no more than 91.0 kg.
• Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator.
• Systolic blood pressure between 95-140 mmHg, inclusive, and diastolic blood pressure between 55-90 mmHg, inclusive, oxygen saturation level between 95% and 100%, inclusive, and heart rate between 55-100 bpm, inclusive, unless deemed otherwise by the PI/Sub-Investigator.
• Clinical laboratory values within BPSI's most recent acceptable laboratory test range, and/or values are deemed by the PI/Sub-Investigator as "Not Clinically Significant".
• Ability to comprehend and be informed of the nature of the study, as assessed by BPSI staff. Capable of giving written informed consent prior to any study related procedure. Must be able to communicate effectively with clinic staff.
• Ability to fast for at least 10 hours and consume standard meals.
• Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.
• Agree not to have a tattoo or body piercing until the end of the study.
• Agree not to receive COVD-19 vaccination from 7 days prior to first study drug administration until 7 days after the last study drug administration or the last procedure in the study, whichever is later.
• Agree not to receive a vaccination (live attenuated vaccine) during the study and until 60 days after the study has ended (last study procedure)
• Female subjects must be non-pregnant and non-lactating and fulfil at least one of the following:
• Be surgically sterile for a minimum of 6 months (achieved through partial or total hysterectomy, bilateral oophorectomy, or bilateral salpingectomy; note that tubal ligation is not considered a method of permanent sterilization).

You may not qualify if:

• Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator.
• Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within 7 days prior to first study drug administration, as determined by the PI/Sub-Investigator.
• Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
• Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
• A known history or positive test result for human immunodeficiency virus (HIV), chronic Hepatitis B surface antigen, or Hepatitis C.
• A positive test result for drugs of abuse/recreational drugs (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines), alcohol test and cotinine. Positive pregnancy test for female subjects of childbearing potential.
• Known history or presence of:
• Alcohol abuse or dependence within one year prior to first study drug administration;
• Drug abuse or dependence;
• Known hypersensitivity or idiosyncratic reaction to PPI-1011, its excipients (e.g., liquid coconut oil, 1-thioglycerol etc), and/or related substances;
• Food allergies;
• Presence of any dietary restrictions unless deemed by the PI/Sub-Investigator as "Not Clinically Significant";
• Severe allergic reactions (e.g. anaphylactic reactions, angioedema).
• Intolerance to and/or difficulty with blood sampling through venipuncture.
• Abnormal diet patterns (for any reason) during the four weeks preceding the study, including fasting, high protein diets etc.

Sponsors & Collaborators

• MED-LIFE DISCOVERIES LP: lead
• BioPharma Services Inc.: collaborator

Study Sites (1)

Biopharma Services Inc.

Toronto, Ontario, M9L 3A2, Canada

RECRUITING

MeSH Terms

Conditions

Chondrodysplasia Punctata, Rhizomelic

Interventions

PPI-1011

Condition Hierarchy (Ancestors)

Chondrodysplasia Punctata; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Peroxisomal Disorders; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Tara Smith, PhD

  MED-LIFE DISCOVERIES LP

  STUDY DIRECTOR

Central Study Contacts

Vaithiegaa Mathanarajan

CONTACT

+1 437 213 1750; vmathanarajan@biopharmaservices.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of 5 planned single-dose cohorts (n = 8 per cohort, total randomized 6 active: 2 placebo) with sentinel design followed by 2 multiple-dose cohorts (n = 8 per cohort, total randomized 6 active: 2 placebo).

Study Record Dates

• First Submitted: June 11, 2023
• First Posted: August 1, 2023
• Study Start: May 29, 2023
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)