Title
LYT-100 in Healthy Volunteers and BCRL
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
Phase
Phase 1Lead Sponsor
PureTechStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Lymphoedema Breast Cancer Related LymphoedemaIntervention/Treatment
LYT-100 ...Study Participants
50Part 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
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.
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.
Inactive capsule(s)
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
BCRL patients will receive LYT-100 BID for 6 months
BCRL patients will receive Placebo BID for 6 months
Placebo, multiple administrations
LYT-100, Dose below MTD for 1 dose
Placebo, for 1 administration
LYT-100, Dose below MTD for 1 dose
Placebo, for 1 administration
Main Inclusion Criteria: Part 1 and 2: Healthy Volunteers Male or female between 18 and 75 years old (inclusive) at the time of screening. 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 Female or male between 18 and 80 years old (inclusive) at the time of informed consent. 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. 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. 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. 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. Documented evidence of Stage 1 or 2 lymphedema. 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 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. Clinically significant infection within 28 days of the start of dosing, or infections requiring parenteral antibiotics within the 6 months prior to screening. 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). History or presence at screening or baseline of a condition associated with significant immunosuppression Part 3: Patients with BRCL 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. 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. 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. Stage III lymphoedema, or history of clinically diagnosed secondary lymphoedema greater than 4 years, determined at screening. 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.
