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A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of SM04646 Inhalation Solution in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03591926
Recruitment Status : Withdrawn (Study withdrawn for business reasons prior to screening or enrolling any subjects.)
First Posted : July 19, 2018
Last Update Posted : October 9, 2018
Sponsor:
Information provided by (Responsible Party):
Samumed LLC

Tracking Information
First Submitted Date  ICMJE July 9, 2018
First Posted Date  ICMJE July 19, 2018
Last Update Posted Date October 9, 2018
Estimated Study Start Date  ICMJE January 1900
Estimated Primary Completion Date January 1900   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
  • Safety and tolerability: treatment-emergent adverse events (TEAEs) [ Time Frame: Week 24 ]
    Evaluate the safety and tolerability of SM04646 as measured by TEAEs during the entire treatment period
  • Safety and tolerability: number of subjects with a clinically significant change from baseline in clinical laboratory tests [ Time Frame: Week 24 ]
    Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in clinical laboratory tests
  • Safety and tolerability: number of subjects with a clinically significant change from baseline in vital signs [ Time Frame: Week 24 ]
    Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in vital signs
  • Safety and tolerability: number of subjects with a clinically significant change from baseline in oxygen saturation [ Time Frame: Week 24 ]
    Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in oxygen saturation
  • Safety and tolerability: number of subjects with a clinically significant change from baseline in electrocardiogram (ECG) parameters [ Time Frame: Week 24 ]
    Evaluate the safety and tolerability of SM04646 as measured by the number of subjects with a clinically significant change from baseline in ECG parameters
  • Plasma pharmacokinetics (PK): Cmax [ Time Frame: Baseline and Week 10 ]
    Measure maximum observed concentration of SM04646 (Cmax) in blood plasma
  • Plasma PK: tmax [ Time Frame: Baseline and Week 10 ]
    Measure time to SM04646 Cmax in blood plasma
  • Plasma PK: AUC [ Time Frame: Baseline and Week 10 ]
    Measure the area under the plasma concentration-time curve (AUC) for SM04646 in blood plasma
  • Plasma PK: t 1/2 [ Time Frame: Baseline and Week 10 ]
    Measure the terminal phase half-life (t 1/2) of SM04646 in blood plasma
  • Plasma PK: accumulation ratio [ Time Frame: Baseline and Week 10 ]
    Measure the accumulation ration of SM04646 in blood plasma
  • Change from baseline in concentration of SM04646 in BAL fluid ("BAL" arm only) [ Time Frame: Baseline and Week 2 ]
    Measure concentration of SM04646 in BAL fluid prior to dosing and after two weeks of dosing
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03591926 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
  • Change from baseline of forced vital capacity (FVC) (% predicted) [ Time Frame: Baseline and Week 24 ]
  • Change from baseline of FVC (liters) [ Time Frame: Baseline and Week 24 ]
  • Categorical analysis of FVC (% predicted) change [ Time Frame: Baseline and Week 24 ]
    Categories measured as "improved", "stable", "moderate decline", or "severe decline"
  • Time to disease progression [ Time Frame: Week 24 ]
    Disease progression as defined by death, absolute decline ≥ 10% in FVC (% predicted), or respiratory hospitalization
  • Change from baseline of forced expiratory volume in 1 second (FEV1) (% predicted) [ Time Frame: Baseline and Week 24 ]
  • Change from baseline of FEV1 (liters) [ Time Frame: Baseline and Week 24 ]
  • Change from baseline of diffusion capacity of the lung for carbon monoxide (DLCO) (% predicted corrected for hemoglobin) [ Time Frame: Baseline and Week 24 ]
  • Change from baseline of quantitative high-resolution computed tomography (HRCT) (%) and mL) [ Time Frame: Baseline and Week 24 ]
  • Change from baseline of quantitative high-resolution computed tomography (HRCT) (mL) [ Time Frame: Baseline and Week 24 ]
  • Change from baseline of qualitative HRCT [ Time Frame: Baseline and Week 24 ]
    Change measured as "improved", "same" or "worse"
  • Change from baseline of biomarker concentration isolated from serum [ Time Frame: Baseline and Week 24 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of SM04646 Inhalation Solution in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Official Title  ICMJE A Phase 2a, 24-Week, Multi-Center, Open-Label Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of SM04646 Inhalation Solution in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Brief Summary

SM04646-IPF-03 is a Phase 2a, multi-center, open-label study evaluating the safety and efficacy of a single inhaled, nebulized dose of SM04646 solution over a 12-week treatment regimen in subjects with mild to moderate IPF. A total of approximately 24 subjects will be enrolled in the study (approximately 12 subjects into the "non-bronchoalveolar lavage [BAL]" arm and approximately 12 subjects into the "BAL" arm). Subjects that currently do not require, have failed to tolerate, or have opted not to have treatment with pirfenidone or nintedanib will have the option of participation in the "BAL" arm or participation in the "non-BAL" arm. Subjects currently receiving treatment with pirfenidone or nintedanib must be on stable treatment for a minimum of 12 weeks prior to the Screening Visit. Subjects currently on treatment with pirfenidone or nintedanib may participate in the "non-BAL" arm only.

Eligible subjects will participate in a treatment period of 12 weeks and a follow-up period of 12 weeks. The treatment dosing pattern will follow a 2 weeks on, 2 weeks off regimen, wherein subjects will dose 5 consecutive days of each 7 day "on" week.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Pulmonary Fibrosis
Intervention  ICMJE Drug: SM04646
Nebulized, inhaled solution; single dose concentration dosed once per day for 12 weeks; dosing pattern will follow a 2 weeks on, 2 weeks off regimen, wherein subjects will dose 5 consecutive days of each 7 day "on" week.
Study Arms  ICMJE
  • Experimental: "BAL" Arm
    Subjects in this arm will undergo a bronchoalveolar lavage (BAL) procedure at baseline and after two weeks of treatment.
    Intervention: Drug: SM04646
  • Experimental: "Non-BAL" Arm
    Subjects in this arm will not undergo any BAL procedures.
    Intervention: Drug: SM04646
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 Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 2, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2018)
24
Estimated Study Completion Date  ICMJE January 1900
Estimated Primary Completion Date January 1900   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • IPF diagnosis within 5 years of study start based upon thoracic society guidelines and confirmed by Investigator at study start
  • Able to walk > 150 m in 6 Minute Walk Test without the use of supplemental oxygen at study start
  • Has a life expectancy of at least 12 months in the opinion of the Investigator
  • Full understanding of the requirements of the study and willingness and ability to comply with all study visits and procedures
  • Able to comprehend and willing to sign an informed consent form (ICF) prior to any study-related procedure being performed
  • Able to tolerate and complete placebo (vehicle) inhalation for 10 minutes without experiencing a significant cough, in the opinion of the Investigator
  • Subjects currently treated with pirfenidone or nintedanib must be willing to remain on their current treatment for the duration of the protocol, unless they experience rapid progression, or if, in the opinion of the Investigator, treatment adjustments are necessary

Exclusion Criteria:

  • Women who are pregnant or lactating
  • Women of childbearing potential who are sexually active and are not willing to use an appropriate method of birth control during the study treatment period until 90 days post study medication administration
  • Males who are sexually active and not willing to use a condom, and have a partner who is capable of becoming pregnant, if neither has had surgery to become sterilized, and/or who are not willing to use an appropriate method of birth control during the study treatment period until 90 days post study medication administration
  • Males unwilling to refrain from sperm donation during the study treatment period until 90 days post study medication administration
  • Subjects unwilling to refrain from blood and plasma donation during the study treatment period until 90 days post study medication administration
  • A history of abuse of prescription or illicit drugs within 6 months prior to study start
  • Positive urine drug and alcohol screen with the exception of positive findings related to current prescription therapy at study start
  • Occurrence of serious illness requiring hospitalization within 90 days prior to study start
  • Presence of active infections at study start
  • Current smoker or past history of smoking (e.g., cigarettes, e-cigarettes, pipes, cigars) within 6 months of study start or >50 pack years
  • Use of non-inhaled tobacco- or nicotine-containing products (e.g., chewing tobacco, nicotine gum, lozenges, or patches) within 30 days prior to study start until completion of the study
  • Regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 30 days prior to study start until completion of the study
  • Lung transplantation anticipated during the duration of the trial
  • Subjects receiving treatment with pirfenidone or nintedanib that:

    1. Have been on treatment for less than 12 weeks prior to study start
    2. Have not been on a stable dose for at least 30 days prior to study start
  • Subjects who are not currently on but have previously received pirfenidone or nintedanib that have not been off of pirfenidone or nintedanib for at least 30 days prior to study start
  • Receipt of any of the following medication or treatment prior to study start:

    1. N-acetylcysteine prescribed for the treatment of IPF within 30 days prior to study start
    2. Previous therapeutic radiation treatment of the lungs, mediastinum, or chest wall
    3. Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure within 30 days or 5 half-lives of the investigational product (if known), whichever is longer, prior to study start
    4. Immunosuppressive medications [e.g., methotrexate, cyclosporine, azathioprine, systemic or inhaled glucocorticosteroids with the exception of short term use of systemic glucocorticosteroids less than or equal to 10 mg of prednisone daily (or equivalent) for a non-IPF condition such as an allergic reaction or rash] within 8 weeks prior to study start
    5. Use of any therapy targeted to treat IPF (including but not limited to d-penicillamine, endothelium receptor antagonist [e.g., bosentan, ambrisentan], and interferon gamma-1B) within 30 days prior to study start
    6. Use of any cytokine modulator (etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab, rituximab) within 90 days or 5 half-lives, whichever is longer, prior to study start
    7. A bronchodilator used within 1 week of study start
    8. SM04646
  • A "bronchodilator response" at study start, defined by an absolute increase of ≥ 12% and an increase of 0.2 L in FEV1 or FVC, or both, after bronchodilator use compared with the values before bronchodilator use
  • History of any of the following conditions:

    1. Pulmonary embolism or pulmonary hypertension
    2. Creatinine clearance of less than 50mL per minute
    3. Active tuberculosis (TB) infection or history of incompletely treated latent TB infection
    4. History of malignancy within the last 5 years; however, the following subjects are eligible:

      1. Subjects with prior history of in situ cancer or basal or squamous cell skin cancer that has been completely excised
      2. Subjects with other malignancies if they have been continuously disease free for at least 5 years prior to any study drug administration
      3. Subjects with prostate cancer followed by surveillance.
    5. Any connective tissue disease, including but not limited to scleroderma, systemic lupus erythematosus, rheumatoid arthritis, and polymyositis/dermatomyositis
    6. Congenital respiratory conditions (e.g., cystic fibrosis)
    7. Chronic obstructive pulmonary disease (COPD) or asthma
    8. Current or recent respiratory tract infection (e.g., pneumonia, purulent bronchitis, or viral upper respiratory tract infection) within 30 days prior to study start
    9. Acute exacerbation of IPF, in the opinion of the Investigator, within 30 days prior to study start
    10. Human immunodeficiency virus (HIV), hepatitis C, or active hepatitis B infection
    11. Clinically significant hepatic impairment (e.g., Child-Pugh A or greater severity)
    12. Symptomatic coronary artery disease, congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, myocardial infarction (MI), or unstable angina within 6 months prior to study start
    13. Hypertension (systolic blood pressure (SBP) >160 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) >100 mmHg)
    14. Hypotension (blood pressure (BP) less than 90/60 mmHg) or mean arterial blood pressure (MAP) < 65 mmHg
    15. Current use of supplemental oxygen therapy for any condition
  • Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the investigative site, or are directly affiliated with the study at the investigative site
  • Subjects employed by Samumed Pacific Pty Ltd, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (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 Australia,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03591926
Other Study ID Numbers  ICMJE SM04646-IPF-03
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
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Samumed LLC
Study Sponsor  ICMJE Samumed LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Yusuf Yazici, M.D. Samumed LLC
PRS Account Samumed LLC
Verification Date October 2018

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