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The Effect of FP-025, a MMP-12 Inhibitor, on Allergen-induced Airway Responses and Airway Inflammation in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma

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ClinicalTrials.gov Identifier: NCT03858686
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
Foresee Pharmaceuticals Co., Ltd.

Tracking Information
First Submitted Date  ICMJE August 9, 2018
First Posted Date  ICMJE March 1, 2019
Last Update Posted Date April 20, 2022
Actual Study Start Date  ICMJE July 2, 2018
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2019)
The primary end point of this study is to determine the effect of FP-025 versus placebo on the allergen (HDM)-induced late asthmatic response (LAR) in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 days) for both Period 1 and Period 2 ]
Late asmatic response (LAR) is defined as FEV1 AUC3-8h; differences between FP025 and placebo
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2019)
  • Pharmacodynamic endpoints include the effect of study treatments on allergen (HDM)-induced changes in LAR. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 days) for both Period 1 and Period 2 ]
    Measurement of LAR is defined as max% fall in FEV1 from post-diluent baseline 3-8 h post-allergen.
  • Pharmacodynamic endpoints include the effect of study treatments on allergen (HDM)-induced changes in Early asthmatic response (EAR). [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 days) for both Period 1 and Period 2 ]
    Measurement of EAR is defined as FEV1 AUC0-3h post-allergen and in max% fall from post-diluent baseline 0-3 h post-allergen.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 26, 2019)
  • Pharmacodynamic endpoints include the effect of study treatments on allergen (HDM)-induced changes in joint HDM-induced airway response. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 days) for both Period 1 and Period 2 ]
    Joint HDM-induced airway response expressed as FEV1 AUC0-8h post-allergen.
  • Pharmacodynamic endpoints include the effect of study treatments on allergen (HDM)-induced changes in airway hyper-responsiveness [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 days) for both Period 1 and Period 2 ]
    Changes in allergen-induced AHR as measured by PC20FEV1(Meth) pre-post allergen (Day 10 versus Day12)
  • Pharmacodynamic endpoints include the effect of study treatments on allergen (HDM)-induced changes in small airway parameters following HDM-challenge. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 days) for both Period 1 and Period 2 ]
    Small airway parameters measured by IOS during LAR and during EAR and over 0-8 h post-allergen challenge.
  • Pharmacodynamic endpoints include the effect of study treatments on allergen (HDM)-induced changes in fractionated nitric oxide (FeNO) and blood eosinophils. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Changes in blood eosinophils, FeNO and PC20FEV1(Meth) Day 1 versus Day 10 (potential treatment effect).
  • To determine the treatment effect (FP-025 versus placebo) on baseline parameters (i.e. Day 1 versus Day 10), through measurement of blood eosinophils. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
  • To determine the treatment effect (FP-025 versus placebo) on baseline parameters (i.e. Day 1 versus Day 10), through measurement methacholine challenge (PC20FEV1 (Meth)). [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    challenge will be discontinued if a fall in FEV1 of ≥20% from post-diluent baseline has been reached, or until the highest concentration has been administered.
  • To determine the treatment effect (FP-025 versus placebo) on baseline parameters (i.e. Day 1 versus Day 10) , through measurement of Fractionated nitric oxide (FeNO). [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    FeNO is measured from exhaled air by Niox Vero® device (Circassia, Oxford, United Kingdom) according to guidelines
  • To evaluate the safety and tolerability of multiple oral doses of FP-025 versus placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Safety parameters include physical examination.
  • To evaluate the safety and tolerability of multiple oral doses of FP-025 versus placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Safety parameters include clinical signs/symptoms reporting (MedDRA).
  • To evaluate the safety and tolerability of multiple oral doses of FP-025 versus placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Safety parameters include Serious Adverse Events (SAEs).
  • To evaluate the safety and tolerability of multiple oral doses of FP-025 versus placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Safety parameters include vital signs.
  • To evaluate the safety and tolerability of multiple oral doses of FP-025 versus placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Safety parameters include lung function measurements.
  • Safety and tolerability of multiple oral doses of FP-025 versus placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Safety parameters include clinical safety laboratory outcomes (blood/urine).
  • To evaluate the safety and tolerability of multiple oral doses of FP-025 versus placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Safety parameters include ECG.
  • Pharmacokinetics of multiple oral doses of FP-025 following inhaled HDM-challenge in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Pharmacokinetic parameter measures of FP-025 in blood (plasma) include Cmax.
  • Pharmacokinetics of multiple oral doses of FP-025 following inhaled HDM-challenge in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Pharmacokinetic parameter measures of FP-025 in blood (plasma) include tmax.
  • Pharmacokinetics of multiple oral doses of FP-025 following inhaled HDM-challenge in subjects with clinically stable, mild allergic asthma and blood eosinophilia. [ Time Frame: From Day 1 through End of Study Visit (EOS) (26 ± 2 day) for both Period 1 and Period 2 ]
    Pharmacokinetic parameter measures of FP-025 in blood (plasma) include AUC0-tau.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE The Effect of FP-025, a MMP-12 Inhibitor, on Allergen-induced Airway Responses and Airway Inflammation in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Official Title  ICMJE The Effect of FP-025, a MMP-12 Inhibitor, on Allergen-induced Airway Responses, Airway Inflammation and Aspects of Airway Remodeling in Subjects With Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Brief Summary This study is a Phase IIa, randomized, placebo-controlled, double-blind, 2-way crossover, 2-center (conducted in EU; The Netherlands) study in male and female subjects with stable, mild HDM-allergic asthma. The study will consist of two identical study periods of 12 treatment days each, separated by a washout period of at least 3 weeks (and no more than 7 weeks). Approximately 36 eligible subjects will be enrolled, to yield 32 evaluable subjects who will be treated with both FP-025 (400 mg BID) or matching placebo in a cross-over design from the evening of Day 1 till the morning of Day 12 (22 doses per study period in total).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Asthma, COPD
Intervention  ICMJE
  • Drug: FP-025 capsules
    FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days.
  • Drug: Placebo FP-025 capsules
    Placebo FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days.
Study Arms  ICMJE
  • Active Comparator: 400 mg FP-025 capsules
    Based on a double-blind randomized schedule, 16 subjects will receive FP-025 capsules in Period 1 and matching placebo FP-025 capsules in Period 2. Both study periods will follow the same schedule of procedures, with a washout period of at least 3 weeks and up to 7 weeks between study periods.
    Interventions:
    • Drug: FP-025 capsules
    • Drug: Placebo FP-025 capsules
  • Placebo Comparator: FP-025 Placebo Capsules
    Based on a double-blind randomized schedule, 16 subjects will receive matching placebo FP-025 capsules in Period 1 and FP-025 capsules in Period 2. Both study periods will follow the same schedule of procedures, with a washout period of at least 3 weeks and up to 7 weeks between study periods.
    Interventions:
    • Drug: FP-025 capsules
    • Drug: Placebo FP-025 capsules
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: February 26, 2019)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

The following criteria must be met by all subjects considered for study participation:

  1. Females or males, between 18 and 55 years of age at Screening, inclusive, on the day of signing the Informed Consent Form (ICF).
  2. Apart from a clinically stable asthma and HDM-allergy, subjects should be generally healthy with no history of a clinically relevant medical condition that in the opinion of the investigator might interfere with successful study conduct and no clinically relevant abnormalities on medical history, physical exam, vital signs, laboratory parameters or ECG at Screening.
  3. Subject has a BMI ≥ 18.0 kg/m2 and ≤ 32.0 kg/m2 (and weighs ≥50 kg).
  4. Subjects have been diagnosed with asthma cf GINA guidelines.
  5. Subjects should have established allergy for HDM (serum HDM-specific IgE or positive SPT at Screening or documented within 1 year pre-screening).
  6. No severe exacerbation of asthma within past 1 year requiring hospital admission and/or treatment with oral corticosteroids; no (never) intensive care admissions for asthma or intubation).
  7. FEV1 should be ≥70% of predicted on Screening Day 2.
  8. On Screening Day 2, PC20FEV1(Meth) should be <16 mg/mL if methacholine chloride is used (or adjusted by a factor of 1.2 if methacholine bromide is used).
  9. Baseline blood eosinophils should be ≥150 cells/μL at Screening or documented within 3 months before Screening Day 1.
  10. Subjects should have a documented airway late response to inhaled HDM on Screening Day 3.
  11. Subjects of childbearing potential must be willing to use adequate contraception (double-barrier) or must refrain from intercourse.
  12. Female subjects of non-childbearing potential must have had

    ≥ 12 months of spontaneous amenorrhea (with folliclestimulating hormone [FSH] ≥ 30 mIU/mL). Surgically sterile women are defined as those who have had a hysterectomy, bilateral ovariectomy (for 'benign' reasons), or bilateral tubal ligation.

  13. All female subjects should have a negative pregnancy test at Screening and on Day -1.
  14. Negative alcohol breath test on Screening Day 1 and Day -1.
  15. Negative cotinine test on Screening Day 1 and Day -1.
  16. Negative urine drug screen for recreational and other drugs on Screening Day 1 and Day -1.
  17. Subjects are non-smokers. A non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to Screening Day 1. Number of years smoked x number of packs per day should be <5 pack years.
  18. Subject should be willing and able to perform the lung function tests and other study-related procedures and comply with study protocol requirements.
  19. Subject should provide a signed and dated informed consent.

Exclusion Criteria:

Subjects will be excluded if they meet any of the following criteria:

  1. Subject has any active and/or chronic (physical or mental) condition requiring maintenance (pharmaco)therapy or which otherwise precludes subject from safe or adequate study participation (ineligibility will be assessed by the PI).
  2. Subject has a history of cancer (exception: localized basalioma or cervix carcinoma in situ).
  3. Subject had any major (nasal) surgery in the 6 months before Screening Day 1.
  4. Subject is pregnant or lactating.
  5. Subject is using immunotherapy that according to the PI may interfere with the study (e.g. in case of immunotherapy with HDM or when subject is in the updosing phase of any immunotherapy).
  6. Subject regularly used alcohol (intake of >21 units/wk for males and >14 units/wk for females) and/or recreational drugs within the last 6 months prior to screening.
  7. Subject had any respiratory (viral) infections (e.g. common cold) within 3 weeks of Screening Day 1 or on Day -1.
  8. Subject is using maintenance asthma therapy or long-acting bronchodilators or any other anti-asthma or anti-allergic medications (as detailed in the protocol) other than infrequent use of SABA prn only.
  9. Subject is using prohibited medications as detailed in the protocol.
  10. Multi-sensitized symptomatic subjects with seasonal (pollen) allergies should be included outside of the relevant allergen season and/or should not be in frequent contact with the relevant allergen during the study.
  11. Subject has any known allergic response for the medications used or known severe allergic reactions or anaphylaxis (to food/medications/insect venoms).
  12. Subject participated in medical studies in the past 3 months (non-biologicals) or in the past 6 months (biologicals).
  13. Subject is anticipated not to comply with study medication or other aspects of the study (at the discretion of the investigator).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Susan Shelby, Ph.D. 302 690-2258 susan.shelby@foreseepharma.com
Contact: Cindy Lopez 650-576-8276 cindy.lopez@foreseepharma.com
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03858686
Other Study ID Numbers  ICMJE FP02C-18-001
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: Undecided
Current Responsible Party Foresee Pharmaceuticals Co., Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Foresee Pharmaceuticals Co., Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Zuzana Diamant, MD, PhD QPS Netherlands
Principal Investigator: Rene Lutter Academic Medical Centre/University of Amsterdam
PRS Account Foresee Pharmaceuticals Co., Ltd.
Verification Date April 2022

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