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LYT-100 in Healthy Volunteers and BCRL

Sponsor
PureTech (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04243837
Collaborator
Novotech (Australia) Pty Limited (Industry)
100
Enrollment
7
Locations
8
Arms
28
Anticipated Duration (Months)
14.3
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Part 1 is a multiple ascending dose trial in healthy volunteers (HV) of LYT-100 to determine safety, tolerability, and pharmacokinetic (PK) profile under fed conditions.

Part 2 is a single dose safety, tolerability, and PK trial in HV of LYT-100 under fed and fasted conditions.

Part 3 is a trial of up to 6-months duration for safety, tolerability, clinical efficacy assessments, PK and biomarkers analysis in breast carcinoma patients with secondary lymphoedema

Condition or Disease Intervention/Treatment Phase
  • Drug: LYT-100
  • Other: Matching Placebo
  • Drug: LYT-100 Food Effect
  • Drug: LYT-100 BCRL
  • Drug: Placebo BCRL
 Phase 1/Phase 2

Detailed Description

Part 1: This is a randomised, double-blind, placebo-controlled, multiple ascending dose design to assess the safety, tolerability and PK profile of multiple doses of LYT-100 administered under fed conditions at steady state in healthy participants. Up to 4 dosing cohorts are planned.

Part 2: A dose level below the MTD in Part 1 will be used in Part 2. Subjects will be administered a single dose of their assigned treatment under fasting conditions followed by a wash out period then they will receive a single dose of the same assigned treatment under fed conditions. This will permit a comparison of the PK profile and bioavailability in both fed and fasted states. .

Part 3: Once the optimal dose and regimen is determined with or without food, Part 3 will follow with a randomised, double-blinded, placebo controlled design that will assess the safety, tolerability, and secondarily clinical efficacy of LYT-100 over a period of up to 6-months of dosing in breast carcinoma patients with secondary lymphoedema following sentinel lymph node biopsy and/or axillary node dissection, with or without radiation.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Part 1 consists of 5 cohorts with active treatment or placebo Part 2 consists of 1 cohort with active treatment or placebo Part 3 consists of 1 cohort with active treatment or placeboPart 1 consists of 5 cohorts with active treatment or placebo Part 2 consists of 1 cohort with active treatment or placebo Part 3 consists of 1 cohort with active treatment or placebo
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
Part 1 and Part 2 are double-blind during the data collection. Determination for dose escalation maybe made under unblinded conditions by assessors. Part 3 is double-blinded
Primary Purpose:
Treatment
Official Title:
A Phase 1 Multiple Ascending Dose and Food Effect Study in Healthy Volunteers to Determine the Pharmacokinetics and Maximally Tolerated Dose of Deupirfenidone (LYT-100) Followed by a Randomized Double-Blind Placebo-Controlled Phase 2a in Patients With Breast Cancer-Related Upper Limb Secondary Lymphoedema
Actual Study Start Date :
Mar 1, 2020
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: LYT-100 in healthy volunteers with Food

LYT-100, multiple ascending

Drug: LYT-100
LYT-100 is a deuterated form of pirfenidone, an orally active small molecule drug. HV subjects will receive multiple ascending doses, starting at 100 mg BID up to 1000 mg, with food for 5-days.
Other Names:
  • Deupirfenidone

    		•
    Placebo Comparator: Placebo in healthy volunteers with Food

    Placebo, multiple administrations

    Other: Matching Placebo
    Inactive capsule(s)
    Experimental: LYT-100 in healthy volunteers, Fasted

    LYT-100, Dose below MTD for 1 dose

    Drug: LYT-100 Food Effect
    LYT-100 is a deuterated form of pirfenidone, an orally active small molecule drug. HV subjects will receive one dose of LYT-100 or Placebo
    Other Names:
  • Deupirfenidone

    		•
    Placebo Comparator: Placebo in healthy volunteers, Fasted

    Placebo, for 1 administration

    Drug: LYT-100 Food Effect
    LYT-100 is a deuterated form of pirfenidone, an orally active small molecule drug. HV subjects will receive one dose of LYT-100 or Placebo
    Other Names:
  • Deupirfenidone

    		•
    Experimental: LYT-100 in healthy volunteers, Fed

    LYT-100, Dose below MTD for 1 dose

    Drug: LYT-100 Food Effect
    LYT-100 is a deuterated form of pirfenidone, an orally active small molecule drug. HV subjects will receive one dose of LYT-100 or Placebo
    Other Names:
  • Deupirfenidone

    		•
    Placebo Comparator: Placebo in healthy volunteers, Fed

    Placebo, for 1 administration

    Drug: LYT-100 Food Effect
    LYT-100 is a deuterated form of pirfenidone, an orally active small molecule drug. HV subjects will receive one dose of LYT-100 or Placebo
    Other Names:
  • Deupirfenidone

    		•
    Experimental: LYT-100 in patients with BCRL

    LYT-100 BID for 6 months

    Drug: LYT-100 BCRL
    BCRL patients will receive LYT-100 BID for 6 months
    Other Names:
  • Deupirfenidone

    		•
    Placebo Comparator: Placebo in patients with BCRL

    Placebo BID for 6 months

    Drug: Placebo BCRL
    BCRL patients will receive Placebo BID for 6 months
    Other Names:
  • Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety and tolerability: treatment-emergent adverse events (TEAEs) [7 days (main time frame)]

      Evaluate the safety and tolerability of LYT-100 as measured by TEAEs

    2. Use pharmacokinetics to characterize the plasma concentration of LYT-100 [7 days (main time frame)]

      Measure observed concentration of LYT-100 in blood plasma

    Secondary Outcome Measures

    1. Efficacy signals of LYT-100 [6 months]

      Explore efficacy signals of LYT-100 in breast cancer patients with lymphedema

    2. Effect of food on the pharmacokinetic profile of LYT-100 based on plasma concentration of LYT-100 [2 days (main time frame)]

      Measure concentration of LYT-100 in blood plasma in fed or fasted subjects

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Main Inclusion Criteria:

    Part 1 and 2: Healthy Volunteers

    1. Male or female between 18 and 75 years old (inclusive) at the time of screening.

    2. In good general health at screening, free from clinically significant unstable medical, surgical or psychiatric illness, at the discretion of the Investigator.

    Part 3: Patients with BRCL

    1. Female or male between 18 and 80 years old (inclusive) at the time of informed consent.

    2. At least 6 months since any type of breast cancer surgery (excluding fine needle aspiration biopsy [FNA]), at the time of study screening. No intention to have breast reconstructive surgery, nipple reconstruction and/or tattooing during the course of the study.

    3. At least 3 months since completion of all types of treatment for breast cancer, including but not limited to neoadjuvant, radiotherapy, chemotherapy and immunotherapy, at the time of study screening.

    4. At least 3 months treatment of stable adjuvant treatment with hormonal or anti-HER2 therapy at the time of screening, with no planned changes to this therapy throughout the duration of the study.

    5. Diagnosis of primary breast cancer, and without evidence of recurrence of breast cancer and/or metastasis for at least 6 months since breast cancer surgery, as determined at screening and baseline.

    6. Documented evidence of Stage 1 or 2 lymphedema.

    7. Receiving standard of care compression or agreeable to using care compression, or no compression at all ≥ 4 weeks prior to screening and throughout the study.

    Main Exclusion Criteria:

    Part 1 and 2: Healthy Volunteers

    1. History or presence of malignancy at screening or baseline, with the exception of adequately treated localised skin cancer (basal cell or squamous cell carcinoma) or carcinoma in-situ of the cervix.

    2. Clinically significant infection within 28 days of the start of dosing, or infections requiring parenteral antibiotics within the 6 months prior to screening.

    3. Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within 3 months prior to study drug administration; corticosteroids are permitted at the discretion of the Investigator).

    4. History or presence at screening or baseline of a condition associated with significant immunosuppression

    Part 3: Patients with BRCL

    1. Bilateral lymphoedema or history of bilateral axillary lymph node removal (i.e., sentinel lymph node or axillary lymph node dissection), or primary lymphoedema or lymphatic or vascular malformation, determined at screening.

    2. Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within 3 months prior to study drug administration; corticosteroids are permitted at the discretion of the PI.

    3. Recent history (in the 8 weeks prior to screening) of cellulitis, lymphangitis, dermatitis, necrotizing fasciitis, or current open wounds or sores in the affected extremity.

    4. Stage III lymphoedema, or history of clinically diagnosed secondary lymphoedema greater than 4 years, determined at screening.

    5. Initiated use of compression or manual lymphatic drainage or other lymphoedema therapies at the start of the study within 4 weeks of the screening visit. Rescreening is allowed following a course of stable compression regimen of > 4 weeks.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope National Medical Center Duarte California United States 91010
    2 MACRO Trials Los Angeles California United States 91105
    3 University of the Sunshine Coast Sippy Downs Queensland Australia
    4 Ballarat Health Services Ballarat Victoria Australia
    5 Nucleus Network VIC Melbourne Victoria Australia 3004
    6 Flinders University Adelaide Australia
    7 Macquarie University Health Sciences Centre Sydney Australia

    Sponsors and Collaborators

    • PureTech
    • Novotech (Australia) Pty Limited

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    PureTech
    ClinicalTrials.gov Identifier:
    NCT04243837
    Other Study ID Numbers:
    • LYT-100-2020-01
    First Posted:
    Jan 28, 2020
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Breast Neoplasms
    Lymphedema
    Breast Cancer Lymphedema
    Pirfenidone

    Study Results

    No Results Posted as of Apr 5, 2022