Treatment of Indolent Systemic Mastocytosis With PA101
Primary Purpose
Mastocytosis, Systemic Mastocytosis, Indolent Systemic Mastocytosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PA101
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Mastocytosis focused on measuring mastocytosis, cromolyn sodium
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of indolent systemic mastocytosis (ISM) according to the WHO criteria and the consensus proposal (2001)
- Experiencing at least one predefined qualifying symptom in at least two organ systems within 3 months of Screening despite the use of H1 and/or H2 antihistamines and other anti-mediator therapy
- Experiencing symptoms with a severity score of at least 4 for at least 7 out of 14 days during the Run-in period with at least one predefined qualifying symptom each from at least two organ systems, despite the use of H1 and/or H2 antihistamines and/or other anti-mediator therapy
- Willing and able to use an eDiary device daily for the duration of the study
- Completed at least 5 eDiary reports during each of two consecutive weeks of the Run-in period
- Willing and able to provide written informed consent prior to any study procedures
Exclusion Criteria:
- Advanced systemic mastocytosis (i.e., aggressive systemic mastocytosis [ASM], mast cell leukemia [MCL], or systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease [SM-AHNMD] )
- Current or recent history of clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant, or other illnesses that could put the patient at risk or compromise the quality of the study data as determined by the Investigator
- Use of oral cromolyn sodium within 6 weeks of Screening
- History of systemic corticosteroid, immunosuppressive, or anti-IgE monoclonal antibody therapy (e.g., omalizumab) within 6 months of Screening
- History of anaphylaxis requiring systemic treatment (i.e., corticosteroid or epinephrine) within 12 months of Screening
- Upper or lower respiratory tract infection within 4 weeks of Screening
- History of malignancy within the last 5 years, except basal cell carcinoma or cervix carcinoma in situ
- Major surgery within 6 months of Screening
- Current or recent history (within 12 months) of excessive use or abuse of alcohol
- Current or recent history (within 12 months) of abusing legal drugs or use of illegal drugs or substances
- Pregnant or breastfeeding females, or if of child-bearing potential unwilling to practice acceptable means of birth control or abstinence during the study
- Participation in any other investigational drug study within 4 weeks of Screening
- History of hypersensitivity or intolerance to aerosol medications or cromolyn sodium
Sites / Locations
- Hopital Necker - Enfants Malades
- Charité - Universitätsmedizin Berlin
- Klinikum Darmstadt
- University Medical Center Mainz
- Technical University München
- University of Salerno
- University Medical Center of Groningen
- Hospital Universitario de Fuenlabrada
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
PA101
Placebo
Arm Description
PA101, 40 mg administered via inhalation three times daily for 6 weeks
Placebo, administered via inhalation three times daily for 6 weeks
Outcomes
Primary Outcome Measures
Overall symptom score
Mastocytosis Activity of Symptoms (MAS Plus) questionnaire for daily symptom score using eDiary
Secondary Outcome Measures
Disease specific quality of life (QoL)
Mastocytosis Impact Questionnaire (MIQ) for quality of life
Patient Global Impression of Change (PGIC) scale
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02478957
Brief Title
Treatment of Indolent Systemic Mastocytosis With PA101
Official Title
Randomized, Double-blind, Placebo-controlled, Crossover Design, Efficacy and Safety Study With PA101 in Patients With Indolent Systemic Mastocytosis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
June 2015 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Patara Pharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, placebo- and active-controlled, 2-period crossover, 2 cohort study in adult patients with indolent systemic mastocytosis (ISM).
The purpose of the study is to determine the efficacy and safety profile of PA101 delivered via eFlow high efficiency nebulizer in patients with ISM who are symptomatic despite using standard treatments.
Detailed Description
The symptom scores for determining eligibility will be established during the 2-week Run-in Period using eDiary and the eligible patients will be randomly allocated in a 2:1 ratio to one of two treatment cohorts at the baseline visit.
In Cohort 1 (n=24), patients will receive inhaled 40 mg PA101 three times daily and inhaled placebo three times daily via eFlow for 6 weeks each in a double-blind, 2-period crossover fashion with a 4-week washout period between the treatment periods.
In Cohort 2 (n=12), patients will receive inhaled 40 mg PA101 three times daily via eFlow and oral cromolyn sodium 200 mg four times daily for 6 weeks each in an open label, 2-period crossover fashion with a 4-week washout period between the treatment periods.
Patients will be allowed to use the same daily doses of pre-randomization H1 and H2 antihistamines as well as the same daily doses of any other allowed medications during each treatment period.
Visits during each treatment period will occur at the baseline Visit, and at the end of Weeks 1, 2, 4, and 6.
Blood and urine samples will be collected to test for various biomarkers. In a subset of patients, additional clinical assessments of the skin will be performed and blood samples will be collected for pharmacokinetic assessments. Clinical safety assessments will be performed in all patients at the start and end of each treatment period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mastocytosis, Systemic Mastocytosis, Indolent Systemic Mastocytosis
Keywords
mastocytosis, cromolyn sodium
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PA101
Arm Type
Experimental
Arm Description
PA101, 40 mg administered via inhalation three times daily for 6 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, administered via inhalation three times daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
PA101
Intervention Description
40 mg PA101 administered via inhalation three times daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
matching placebo administered via inhalation three times daily for 6 weeks
Primary Outcome Measure Information:
Title
Overall symptom score
Description
Mastocytosis Activity of Symptoms (MAS Plus) questionnaire for daily symptom score using eDiary
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Disease specific quality of life (QoL)
Description
Mastocytosis Impact Questionnaire (MIQ) for quality of life
Time Frame
6 weeks
Title
Patient Global Impression of Change (PGIC) scale
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of indolent systemic mastocytosis (ISM) according to the WHO criteria and the consensus proposal (2001)
Experiencing at least one predefined qualifying symptom in at least two organ systems within 3 months of Screening despite the use of H1 and/or H2 antihistamines and other anti-mediator therapy
Experiencing symptoms with a severity score of at least 4 for at least 7 out of 14 days during the Run-in period with at least one predefined qualifying symptom each from at least two organ systems, despite the use of H1 and/or H2 antihistamines and/or other anti-mediator therapy
Willing and able to use an eDiary device daily for the duration of the study
Completed at least 5 eDiary reports during each of two consecutive weeks of the Run-in period
Willing and able to provide written informed consent prior to any study procedures
Exclusion Criteria:
Advanced systemic mastocytosis (i.e., aggressive systemic mastocytosis [ASM], mast cell leukemia [MCL], or systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease [SM-AHNMD] )
Current or recent history of clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant, or other illnesses that could put the patient at risk or compromise the quality of the study data as determined by the Investigator
Use of oral cromolyn sodium within 6 weeks of Screening
History of systemic corticosteroid, immunosuppressive, or anti-IgE monoclonal antibody therapy (e.g., omalizumab) within 6 months of Screening
History of anaphylaxis requiring systemic treatment (i.e., corticosteroid or epinephrine) within 12 months of Screening
Upper or lower respiratory tract infection within 4 weeks of Screening
History of malignancy within the last 5 years, except basal cell carcinoma or cervix carcinoma in situ
Major surgery within 6 months of Screening
Current or recent history (within 12 months) of excessive use or abuse of alcohol
Current or recent history (within 12 months) of abusing legal drugs or use of illegal drugs or substances
Pregnant or breastfeeding females, or if of child-bearing potential unwilling to practice acceptable means of birth control or abstinence during the study
Participation in any other investigational drug study within 4 weeks of Screening
History of hypersensitivity or intolerance to aerosol medications or cromolyn sodium
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Siebenhaar, MD
Organizational Affiliation
Charite University, Berlin, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Necker - Enfants Malades
City
Paris
Country
France
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
Klinikum Darmstadt
City
Darmstadt
Country
Germany
Facility Name
University Medical Center Mainz
City
Mainz
Country
Germany
Facility Name
Technical University München
City
Munich
Country
Germany
Facility Name
University of Salerno
City
Salerno
Country
Italy
Facility Name
University Medical Center of Groningen
City
Groningen
Country
Netherlands
Facility Name
Hospital Universitario de Fuenlabrada
City
Madrid
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Treatment of Indolent Systemic Mastocytosis With PA101
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