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Assess the Safety, Tolerability Oral PU-H71 in Subjects Taking Ruxolitinib

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ClinicalTrials.gov Identifier: NCT03935555
Recruitment Status : Recruiting
First Posted : May 2, 2019
Last Update Posted : October 20, 2020
Sponsor:
Information provided by (Responsible Party):
Samus Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE March 14, 2019
First Posted Date  ICMJE May 2, 2019
Last Update Posted Date October 20, 2020
Actual Study Start Date  ICMJE August 12, 2019
Estimated Primary Completion Date May 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
  • Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including Cmax
  • Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including Tmax
  • Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including AUC0-t
  • Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including AUC0-inf
  • Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including CL
  • Assess Safety, Tolerability and Pharmacokinetics of PU-H71 [ Time Frame: 24 weeks ]
    Determine the human exposure PK including t1/2
  • Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in physical examinations
  • Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in electrocardiograms (ECGs)
  • Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in vital signs
  • Assess Safety and Tolerability of PU-H71 [ Time Frame: 24 weeks ]
    Determine the Incidence and severity of AEs as determined by the NCI-CTCAE Version 5.0 and by changes in clinical laboratory evaluations
  • Assess treatment response of PU H71 [ Time Frame: 24 weeks ]
    Treatment response in myelofibrosis (MF) is to be evaluated using the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
  • Assess treatment response of PU H71 [ Time Frame: 24 weeks ]
    Treatment response in myelofibrosis (MF) is to be evaluated using the revised European LeukemiaNet (ELN) response criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assess the Safety, Tolerability Oral PU-H71 in Subjects Taking Ruxolitinib
Official Title  ICMJE Phase 1b Study of PU-H71 for the Treatment of Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF), Treated With Ruxolitinib
Brief Summary This is a multicenter, Phase 1b study with dose escalation and expansion cohorts designed to assess the safety, tolerability, PK, and preliminary efficacy of PU-H71 in subjects with PMF, Post-PV MF, Post-ET MF, taking stable doses of ruxolitinib.
Detailed Description The study will employ a standard 3+3 dose escalation design to determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), with additional subjects treated in a dose expansion cohort. The time period for collecting dose limiting toxicities (DLTs) is 1 cycle (21 days).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
The study will employ a standard 3+3 dose escalation design to determine maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), with additional subjects treated in a dose expansion cohort. The time period for collecting dose limiting toxicities (DLTs) is 1 cycle (21 days).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Myelofibrosis (PMF)
  • Post-Polycythemia Vera Myelofibrosis (Post-PV MF)
  • Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
Intervention  ICMJE Drug: PU-H71
PU-H71 is a synthetic purine-scaffold stress chaperome inhibitor, which specifically targets HSP90 in the tumor-specific epichaperome
Study Arms  ICMJE
  • Experimental: Oral - 50mg
    PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
    Intervention: Drug: PU-H71
  • Experimental: Oral -100 mg
    PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
    Intervention: Drug: PU-H71
  • Experimental: Oral - 200 mg
    PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
    Intervention: Drug: PU-H71
  • Experimental: Oral - 300 mg
    PU-H71 (a small molecule purine-scaffold epichaperome inhibitor selective for stress-induced HSP90 in epichaperomes).
    Intervention: Drug: PU-H71
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 30, 2019)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 15, 2021
Estimated Primary Completion Date May 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject is willing and able to provide written informed consent before any study-specific procedures are performed.
  2. Subject is willing to comply with all study procedures and restrictions.
  3. Subject is ≥18 years of age.
  4. Subject has confirmed diagnosis of PMF, Post-PV MF, or Post-ET MF.
  5. Subject has been receiving ruxolitinib therapy meeting the following criteria:

    • Receiving ruxolitinib >3 months prior to enrollment.
    • Stable dose for 8 weeks before starting therapy with PU-H71.
  6. Subject with evidence of evaluable residual burden of disease following ruxolitinib monotherapy treatment, consisting of:

    • Persistent or worsening disease-related symptoms, including but not limited to fatigue, pruritus, night sweats, early satiety, and other symptoms as determined by a Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) score of >12 points.

    AND

    • Documented splenomegaly of at least 5 cm below the costal margin as measured on inspiration by physical examination.

  7. Subject has an Eastern Cooperative Oncology Group performance status of 0 to 2.
  8. Acceptable pre-study organ function during screening defined as:

    • Absolute neutrophil count (ANC) ≥1000/µL.
    • Platelet count ≥50,000/µL.
    • Alanine aminotransferase or aspartate aminotransferase ≤2×upper limit of normal.
    • Direct serum bilirubin ≤ 1.5×upper limit of normal.
    • Creatinine clearance >50 mL/min/1.73 m2 based on the Cockcroft Gault equation.
  9. If female and of childbearing potential (premenopausal and not surgically sterile), the subject:

    • Must have a negative serum or urine pregnancy test at screening. The serum pregnancy test must be obtained prior to the first administration of PU-H71 (≤72 hours prior to dosing) in all premenopausal women and women <2 years after the onset of menopause.
    • Must agree to use an acceptable method of effective contraception for the duration of the study and for 13 weeks after receiving the last dose of study treatment.
  10. If male, the subject agrees to:

    • Use an acceptable method of effective contraception for the duration of the study and for 13 weeks after receiving study treatment.
    • Agrees to abstain from sperm donation for the duration of the study and for 13 weeks after receiving the last dose of study treatment

Exclusion Criteria:

  1. Subject has known active liver disease, including viral hepatitis or cirrhosis.
  2. Subject has known or suspected human immunodeficiency virus (HIV) or other active infections requiring acute or chronic treatment with systemic antibiotics. Conditions requiring topical antibiotics are acceptable.
  3. Subject has a QT interval corrected using Fridericia's formula (QTcF) >480 ms (corrected) in the screening or baseline ECG based on median value of ECG's obtained.
  4. Subject has left ventricular ejection fraction (LVEF) ≤50%, or below institution's lower limit of normal (whichever is lower), by echocardiogram or multigated acquisition (MUGA) scan.
  5. Subject has a history (or family history) of long QT syndrome.
  6. Subject has coronary artery disease with an ischemic event within 6 months prior to screening.
  7. Subject has a permanent cardiac pacemaker.
  8. Subject has history of a second primary malignancy within the past 2 years, except for the following (if appropriately treated and considered cured): Stage I endometrial, surgically treated cervical or prostate carcinoma, and non-melanoma skin cancer.
  9. Subject has significant uncontrolled medical condition within 6 months prior to screening, as determined by the Investigator.
  10. Subject has planned use of antineoplastic agents (chemotherapy or cytotoxic drugs), immunotherapy, experimental therapy, or biologic therapy for treatment of MPN with the exception of ruxolitinib.
  11. Subject uses systemic corticosteroids (ie, prednisone >12.5 mg/day or dexamethasone >2 mg/day) within 2 weeks prior to Cycle 1 Day 1.
  12. Subject has planned or current use of strong CYP3A4/5, CYP2D6, or CYP2C19 inhibitors or inducers within 1 week or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
  13. Subject has planned or current use of medications that carry a risk for Torsades de Pointes within 1 week or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
  14. Subject has planned or current use of herbal preparations/medications at least 7 days prior to Cycle 1 Day 1.
  15. Subject has previously received PU-H71.
  16. Subject has concurrent participation in any interventional studies (except PU-H71-Positive Emission Tomography (PET) Scan Studies) within 14 days or 5 half-lives (whichever duration is longer) of Cycle 1 Day 1.
  17. Subject has uncontrolled diabetes mellitus, in the judgment of the Investigator.
  18. Subject has any other condition or laboratory abnormality or receives any other treatment(s) that may increase the risk associated with study participation or may interfere with the interpretation of study results in the judgment of the Investigator.
  19. Subject has an active ocular condition that in the opinion of the Investigator, may alter visual acuity during the course of the study (ie, ocular inflammatory disease, etc.) or a history or anticipation of major ocular surgery (including cataract extraction, intraocular surgery, etc.) during the study.
  20. Women who are pregnant or breastfeeding or plan to become pregnant.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Carol Becker 646-902-9376 beckerc@samustherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03935555
Other Study ID Numbers  ICMJE PU-H71-01-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Samus Therapeutics, Inc.
Study Sponsor  ICMJE Samus Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hagop Youssoufian, M.D. Samus Therapeutics
PRS Account Samus Therapeutics, Inc.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP