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Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL

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ClinicalTrials.gov Identifier: NCT02580552
Recruitment Status : Completed
First Posted : October 20, 2015
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
miRagen Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE October 15, 2015
First Posted Date  ICMJE October 20, 2015
Last Update Posted Date November 23, 2020
Actual Study Start Date  ICMJE February 9, 2016
Actual Primary Completion Date October 6, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
Safety and tolerability of cobomarsen based on vital signs, physical examination, clinical laboratory tests, ECG, and incidence and severity of adverse events [ Time Frame: From start of treatment to end of study participation ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
Safety and tolerability of MRG-106 based on vital signs, physical examination, clinical laboratory tests, ECG, and incidence and severity of adverse events [ Time Frame: Up to 56 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2020)
  • Area under the plasma concentration vs. time curve (AUC) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously [ Time Frame: Up to 56 days ]
  • Peak plasma concentration (Cmax) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously [ Time Frame: Up to 56 days ]
  • Trough plasma concentration (Ctrough) of cobomarsen following each 4-week cycle of dosing [ Time Frame: Monthly from Week 5 up to end of study participation ]
  • Skin disease severity (index lesions) - MF only [ Time Frame: Every 2 weeks from start of treatment until end of study participation ]
    Changes in MF skin lesion severity before and after treatment based on the Composite Assessment of Index Lesion Severity (CAILS) score
  • Skin disease severity (whole body) - MF only [ Time Frame: Every 2 weeks from start of treatment until end of study participation ]
    Changes in MF skin lesion severity before and after treatment based on the modified Severity Weighted Assessment Tool (mSWAT) score
  • Overall Response Rate in the skin - MF [ Time Frame: Approximately 1 year ]
    Proportion of subjects who achieve a partial response (PR) or complete response (CR) in the skin, based on SWAT score
  • Overall Response Rate - CLL [ Time Frame: Approximately 1 year ]
    Proportion of subjects who achieve a PR or CR as defined by IWCLL criteria (Hallek et al., 2008) based on CT scans, bone marrow biopsies, and flow cytometry
  • Minimal Residual Disease (MRD) - CLL only [ Time Frame: Approximately 1 year ]
    Proportion of subjects who achieve a CR with no evidence of MRD by flow cytometry
  • Overall Response Rate - DLBCL [ Time Frame: Approximately 1 year ]
    Proportion of subjects who achieve a PR or CR as defined by the Lugano classification (Cheson et al., 2014) based on positron emission tomography-computed tomography (PET-CT) scans and bone marrow biopsy to confirm CR
  • Overall Response Rate - ATLL [ Time Frame: Approximately 1 year ]
    Proportion of subjects who achieve a PR or CR as defined by international consensus criteria (Tsukasaki et al., 2009) based on CT scans and flow cytometry, and bone marrow biopsy to confirm CR
  • Duration of Response [ Time Frame: Up to approximately 2 years ]
    Number of days from initial date of confirmed PR or CR until loss of response or relapse
  • Time to Progression [ Time Frame: Up to approximately 2 years ]
    Number of days from first dose until objective disease progression
  • Progression Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    Number of days from first dose until objective disease progression or death from any cause
  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    Number of days from first dose until death from any cause
Original Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
  • Area under the plasma concentration vs. time curve (AUC) of MRG-106 following single and repeat doses administered intratumorally or subcutaneously [ Time Frame: Up to 56 days ]
  • Peak plasma concentration (Cmax) of MRG-106 following single and repeat doses administered intratumorally or subcutaneously [ Time Frame: Up to 56 days ]
Current Other Pre-specified Outcome Measures
 (submitted: November 19, 2020)
  • miR-155-5p expression in cutaneous lesions of subjects with MF [ Time Frame: At baseline and between Week 16 and end of study participation ]
    Exploratory assessment based on quantitative real time polymerase chain reaction (qRT-PCR) analysis of total RNA isolated from skin biopsies
  • Proportion of neoplastic lymphoid cells in cutaneous lesions of subjects with MF [ Time Frame: At baseline and between Week 16 and end of study participation ]
    Exploratory histological assessment before and after treatment with cobomarsen
  • Proportions of immune cell subsets [ Time Frame: At baseline and monthly or bimonthly, up to end of study participation ]
    Exploratory assessment before and after treatment with cobomarsen by flow cytometry on whole blood
  • Dermatology-specific quality of life - MF only [ Time Frame: At baseline and monthly, up to approximately 2 years ]
    Changes in skin-related quality of life based on the Skindex-29 assessment tool
  • Pruritus - MF only [ Time Frame: At baseline and monthly, up to approximately 2 years ]
    Changes in intensity of skin itch based on the Pruritus Numerical Rating Scale
Original Other Pre-specified Outcome Measures
 (submitted: October 16, 2015)
  • Exploratory assessment of changes in lesion severity before and after treatment based on the Composite Assessment of Index Lesion Severity (CAILS) scoring tool [ Time Frame: Up to 56 days ]
  • Exploratory assessment of changes in lesion severity before and after treatment based on the modified Severity Weighted Assessment Tool (mSWAT) [ Time Frame: Up to 56 days ]
  • Exploratory assessment of miR-155-5p expression in CTCL cutaneous lesions based on quantitative real time polymerase chain reaction (qRT-PCR) analysis of total RNA isolated from skin biopsies [ Time Frame: Up to 56 days ]
  • Exploratory histological assessment of CD4+ cells in CTCL cutaneous lesions before and after treatment [ Time Frame: Up to 56 days ]
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL
Official Title  ICMJE A Phase 1 Dose-ranging Study to Investigate the Safety, Tolerability, and Pharmacokinetics of MRG-106 Following Local Intratumoral, Subcutaneous, and Intravenous Administration in Subjects With Various Lymphomas and Leukemias
Brief Summary Objectives of this clinical trial are to evaluate the safety, tolerability, pharmacokinetics and potential efficacy of the investigational drug, cobomarsen (MRG-106), in patients diagnosed with certain lymphomas and leukemias, including cutaneous T-cell lymphoma (CTCL) [mycosis fungoides (MF) subtype], chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) [activated B-cell (ABC) subtype], and adult T-cell leukemia/lymphoma (ATLL). Cobomarsen is an inhibitor of a molecule called miR-155 that is found at high levels in these types of cancers and may be important in promoting the growth and survival of the cancer cells. Participants in the clinical trial will receive weekly doses of cobomarsen administered by injection under the skin or into a vein, or by injection directly into cancerous lesions in the skin (for CTCL only). Blood samples will be collected to measure how cobomarsen is processed by the body, and other measurements will be performed to study how normal and cancerous cells of the immune system respond when exposed to cobomarsen.
Detailed Description

Study Design:

  • Part A: Cohorts of 3-6 patients diagnosed with MF will receive up to five intratumoral injections of cobomarsen over a period of up to 15 days with follow-up for an additional 20 days, beginning with the maximum deliverable intratumoral dose. Doses may be decreased in subsequent cohorts to determine the minimum pharmacodynamically active dose.
  • Parts B-F: Patients in these parts of the study will be diagnosed with MF (Parts B and C), CLL (Part D), DLBCL (Part E), or ATLL (Part F). All patients will receive subcutaneous or intravenous cobomarsen (or a combination of systemic and intratumoral administration for MF patients only) on Days 1, 3 and 5, and will continue dosing on a weekly schedule until the patient becomes intolerant, develops clinically significant side effects, progresses, or the trial is terminated. Doses administered will not exceed a dose level predicted to be safe based on all prior treatment experience with the drug. Patients in Part B may continue on a stable background therapy for their disease during their treatment with cobomarsen, while patients in Parts C-F will be treated with cobomarsen alone.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cutaneous T-cell Lymphoma (CTCL)
  • Mycosis Fungoides (MF)
  • Chronic Lymphocytic Leukemia (CLL)
  • Diffuse Large B-Cell Lymphoma (DLBCL), ABC Subtype
  • Adult T-Cell Leukemia/Lymphoma (ATLL)
Intervention  ICMJE Drug: Cobomarsen
Other Name: MRG-106
Study Arms  ICMJE
  • Experimental: Part A, MF
    Intratumoral Injection of cobomarsen
    Intervention: Drug: Cobomarsen
  • Experimental: Part B, MF
    Subcutaneous, intravenous or a combination of systemic and intratumoral administration of cobomarsen with or without stable background therapy
    Intervention: Drug: Cobomarsen
  • Experimental: Part C, MF
    Subcutaneous or intravenous administration of cobomarsen as monotherapy
    Intervention: Drug: Cobomarsen
  • Experimental: Part D, CLL
    Subcutaneous or intravenous administration of cobomarsen as monotherapy
    Intervention: Drug: Cobomarsen
  • Experimental: Part E, DLBCL, activated B-cell (ABC) subtype
    Subcutaneous or intravenous administration of cobomarsen as monotherapy
    Intervention: Drug: Cobomarsen
  • Experimental: Part F, ATLL
    Subcutaneous or intravenous administration of cobomarsen as monotherapy
    Intervention: Drug: Cobomarsen
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: November 19, 2020)
66
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2015)
25
Actual Study Completion Date  ICMJE October 6, 2020
Actual Primary Completion Date October 6, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Parts A-C only: Patients must have biopsy proven MF, clinical stage I, II, or III (excluding visceral or nodal involvement), and must be refractory to or intolerant of established therapies for their condition
  • Part D only: Patients diagnosed with CLL who are intolerant to, or have disease that is relapsed/refractory after, at least two prior therapies
  • Part E only: Patients with biopsy-proven DLBCL who are intolerant to, or have disease that is relapsed/refractory after, at least two prior therapies, including any anti-CD20 monoclonal antibody and chemotherapy with curative intent
  • Part F only: Patients with documented HTLV-1 infection and histologically or cytologically proven ATLL of any stage, and who are intolerant to, or have disease that is relapsed/refractory after, at least one prior therapy
  • Females must not be pregnant or lactating. Women of child-bearing potential must use a highly effective method of contraception throughout their study participation and for at least 6 months following the last dose of study drug.
  • Males must be surgically sterile, abstinent, or if engaged in sexual relations with a female of child-bearing potential, must be willing to use a highly effective method of contraception throughout their study participation and for at least 6 months after the last dose of study drug.

Exclusion Criteria:

  • Evidence of renal or liver dysfunction at screening
  • Clinically significant anemia, neutropenia or thrombocytopenia at screening
  • History of bleeding diathesis or coagulopathy
  • Clinically significant cardiovascular disease, history of myocardial infarction within the last 6 months, or evidence of QTc interval prolongation at screening
  • Serologically positive for HIV; serologically positive for Hepatitis B or Hepatitis C with evidence of liver dysfunction or documented liver cirrhosis
  • Prior malignancies within the past 3 years (with allowance for adequately treated in situ carcinoma of the cervix uteri, and basal cell or localized squamous cell carcinoma of the skin treated with curative intent)
  • Use of an investigational small molecule drug during the 30 days prior to screening or use of an investigational oligonucleotide or biologic drug during the prior 90 days
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02580552
Other Study ID Numbers  ICMJE MRG106-11-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party miRagen Therapeutics, Inc.
Study Sponsor  ICMJE miRagen Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Diana M. Escolar, MD, FAAN miRagen Therapeutics, Inc.
PRS Account miRagen Therapeutics, Inc.
Verification Date November 2020

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