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A Phase 2 Study of the Activity and Safety of KD025 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

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ClinicalTrials.gov Identifier: NCT02688647
Recruitment Status : Active, not recruiting
First Posted : February 23, 2016
Last Update Posted : March 9, 2021
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC

Brief Summary:

This Phase 2 study will be conducted to evaluate the safety, tolerability, and activity of 400 mg of KD025 once-daily (QD) compared to Best Supportive Care (BSC) in male and postmenopausal/surgically sterilized female subjects with Idiopathic Pulmonary Fibrosis (IPF). The primary objectives are to evaluate the:

  • Change in forced vital capacity (FVC) from Baseline to 24 weeks after dosing with KD025 400 mg QD in subjects with IPF compared to BSC
  • Safety and tolerability of KD025 400 mg QD when administered for 24 weeks to subjects with IPF compared to BSC

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: KD025 Other: BSC Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase 2, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Actual Study Start Date : May 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: KD025 400 mg Daily
Two 200 mg tablets (400 mg) KD025 QD. Subjects will take 2 tablets with their morning meal or within 5 minutes of completing a meal.
Drug: KD025
Other Name: SLx-2119

Best Supportive Care (BSC)
Best supportive care is treatment and/or drug determined by each subject's prescribing physician.
Other: BSC
Treatment/drug as determined by each subject's prescribing physician
Other Name: Best standard of care




Primary Outcome Measures :
  1. Efficacy: Change in FVC from Baseline to Week 24 [ Time Frame: 24 weeks ]
    1. Forced Vital Capacity (FVC) from Baseline to Week 24;
    2. Group 3 (All KD025-treated) and Group 4 (best supportive care [BSC] without crossover);
    3. Group 1 (KD025 as randomized) and Group 4

  2. Efficacy: Change in FVC% Predicted from Baseline to W24 [ Time Frame: 24 weeks ]
    1. Forced Vital Capacity Predicted (FVC%) from Baseline to Week 24;
    2. Group 3 (All KD025-treated) and Group 4;
    3. Group 1 (KD025 as randomized) and Group 4


Secondary Outcome Measures :
  1. Efficacy: Change in FVC from Baseline to Week 48 and Week 96 [ Time Frame: Up to 96 weeks ]
    Forced Vital Capacity (FVC) from Baseline to Week 48 and Week 96 for Group 1 (KD025 as randomized for 24 weeks) and Group 3 (All KD025-treated subjects)

  2. Efficacy: Change in 6-Minute Walking Distance (6MWD) [ Time Frame: 96 Weeks ]
    The distance traveled during 6 minutes will be measured from Baseline to Week 24, Week 48 and Week 96

  3. Efficacy: DLCO (Corrected for Hb) [ Time Frame: 24 weeks ]

    Analyses as described for FVC at Week 24 for hemoglobin- (Hb-) corrected DLCO using the formula:

    DLCO Predicted Corrected = DLCO Predicted x (1.7 x Hb/[Age-Sex-Factor + Hb) where the age-sex factor was 9.38 for females of any age and children < 15 years old, and the age-sex factor was 10.22 for males >= 15 years old The cutoff criterion for the proportion calculation using a decline of 15% instead of 50 m;


  4. Efficacy: Lung Fibrosis as Measured by Quantitative High Resolution Computer Tomography (HRCT) [ Time Frame: Up to 96 weeks ]
    Change in severity of lung fibrosis will be measured by HRCT from Baseline to Week 24, Week 48, Week 72 and Week 96

  5. Efficacy: Incidence of Acute Exacerbation of IPF [ Time Frame: Up to 96 weeks ]
    Incidence of subjects who had an acute exacerbation of idiopathic pulmonary fibrosis (IPF) throughout treatment period by treatment group and compared by means of a Fisher's exact test on Week 24. Kaplan-Meier curves and descriptive statistics also will be used to summarize time to IPF exacerbation.

  6. Efficacy: Time to IPF Progression [ Time Frame: Up to 96 weeks ]
    Kaplan-Meier curves and descriptive statistics summarizing the time of idiopathic pulmonary fibrosis (IPF) progression. Log-rank testing for comparing treatment differences.

  7. Efficacy: Time to First Respiratory-related Hospitalization [ Time Frame: Up to 96 weeks ]
    Kaplan-Meier curves and descriptive statistics for summarizing the time to first respiratory-related hospitalization. Long-rank testing for comparing treatment differences.

  8. Efficacy: Time to Respiratory-related Death [ Time Frame: Up to 96 weeks ]
    Kaplan-Meier curves and descriptive statistics for summarizing the time to first respiratory-related death. Long-rank testing for comparing treatment differences.

  9. Efficacy: St. George Respiratory Questionnaire [ Time Frame: Up to 96 weeks ]

    The St. George Respiratory Questionnaire (SGRQ) is a standardized self-completed questionnaire for measuring impaired health and perceived well-being in airway diseases. The questionnaire contains multiple sections with differing scales associated with each question to assess how breathing is affecting the subject's life.

    SGRQ is measured at Baseline, Week 12, Week 24, Week 48, and Week 96.


  10. Exploratory: Measurement of Biomarker MMP7 [ Time Frame: Up to 96 weeks ]
    Descriptive statistics (n, mean, SD, median, minimum, maximum) by treatment and study visit for modified metalloproteinase-7 (MMP7)

  11. Exploratory: Measurement of Biomarker CCL 18 [ Time Frame: Up to 96 weeks ]
    Descriptive statistics (n, mean, SD, median, minimum, maximum) by treatment and study visit for chemokine ligand 18 (CCL 18)

  12. Exploratory: Measurement of Biomarker SPD [ Time Frame: Up to 96 weeks ]
    Descriptive statistics (n, mean, SD, median, minimum, maximum) by treatment and study visit for surfactant protein-D (SPD)

  13. Safety: Incidence of AEs Overall, by Intensity, and by Relation to Study Drug [ Time Frame: Up to 104 weeks (96 weeks treatment + 30 day follow-up) ]
    Incidence of adverse events (AEs), as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 22.1, overall, by intensity, and by relationship to study drug.

  14. Safety: Incidence of SAE Overall and by Relation to Study Drug [ Time Frame: Up to 104 weeks (96 weeks treatment + 30-day follow-up) ]
    Incidence of serious adverse events (SAEs), as measured by CTCAE version 22.1, overall and relationship to study drug

  15. Safety: Measurement of ECG Parameters [ Time Frame: Up to 104 weeks (96 weeks treatment + 30-day follow-up) ]
    Measurement of digital 12-lead electrocardiogram (ECG) parameters during the study which include PR interval, QRS interval, and QTcF (QTc interval using Fridericia's correction)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult male and postmenopausal/surgically sterilized female subjects at least 18 years of age (if female, was surgically sterilized [i.e., total hysterectomy, or bilateral salpingo-oophorectomy]).
  • Able to provide written informed consent before the performance of any study specific procedures.
  • IPF diagnosis within 5 years before study entry, proven according to the American Thoracic Society/European Respiratory Society consensus conference criteria, with surgical lung biopsy. In the absence of a surgical lung biopsy, HRCT must have been consistent with usual interstitial pneumonitis.
  • Resting state pulse oximeter oxygen saturation (SpO2) ≥ 88% with or without supplemental oxygen, FVC% ≥ 50% normal predicted value, and DLCO ≥ 30% normal predicted value at baseline.
  • Men with partners of childbearing potential must be willing to use 2 medically acceptable methods of contraception during the trial and for 3 months after the last dose of study drug. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) stable doses of hormonal contraception for at least 3 months (e.g., oral, injectible, implant, transdermal) plus 1 barrier method; (c) 2 barrier methods considered effective are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) vasectomy.
  • Have adequate bone marrow function:

    1. Absolute neutrophil count > 1500/mm^3
    2. Hemoglobin > 9.0 g/L
    3. Platelets > 100,000/mm^3
  • Willing to complete all study measurements and assessments in compliance with the protocol
  • Had either received pirfenidone and/or nintedanib or offered both treatments (with last dose administered at least 1 month before the expected start of study drug dosing). If either or both pirfenidone and nintedanib treatment had not been given, then documentation that the subject was offered both treatments must have been documented.

Exclusion Criteria:

  • Interstitial lung disease caused by conditions other than IPF
  • Severe concomitant illness limiting life expectancy (< 1 year)
  • DLCO < 30% predicted
  • Residual volume ≥ 120% predicted
  • Obstructive lung disease: Forced Expiratory Volume in 1 Second (FEV1_/ FVC ratio < 0.70
  • Documented sustained improvement of the subject's IPF condition up to 12 months before study entry with or without IPF-specific therapy
  • Pulmonary or upper respiratory tract infection within 4 weeks before study entry
  • Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (e.g., pulmonary function tests)
  • Chronic heart failure with New York Heart Association Class III/IV or known left ventricular ejection fraction < 25%
  • Moderate to severe hepatic impairment (i.e., Child-Pugh Class B or C)
  • Estimated creatinine clearance < 30 mL/min
  • Aspartate aminotransferase and/or alanine aminotransferase > 2.0 × upper limit of normal
  • Hemoglobin < 75% of the lower limit of normal
  • Systolic blood pressure < 100 mmHg
  • Female subject who is pregnant or breastfeeding
  • Men whose partner is pregnant or breastfeeding
  • Current drug or alcohol dependence
  • Chronic treatment with the following drugs within 4 weeks of study entry and during the study:

    1. Immunosuppressive or cytotoxic drugs including cyclophosphamide and azathioprine
    2. Antifibrotic drugs including pirfenidone, nintedanib, D-penicillamine, colchicine, tumor necrosis factor-alpha blockers, imatinib, and interferon-γ
    3. Chronic use of N-acetylcysteine prescribed for IPF (> 600 mg/day)
    4. Oral anticoagulants prescribed for IPF
  • Treatment with endothelin receptor antagonists within 4 weeks before study entry
  • Systemic treatment within 4 weeks before study entry with cyclosporine A or tacrolimus, everolimus, or sirolimus (calcineurin or mammalian target of rapamycin inhibitors)
  • Previous exposure to KD025 or known allergy/sensitivity to KD025 or any other Rho-associated protein kinase 2 (ROCK2) inhibitor
  • Planned treatment or treatment with another investigational drug within 4 weeks before study entry
  • Taking a medication with the potential for QTc prolongation
  • Taking a drug sensitive substrate of CYP enzymes
  • Taking a strong inducer of CYP3A4
  • Had consumed an herbal medication (eg, St. John's Wort) or grapefruit/grapefruit juice within 14 days prior to the Week 1 Day 1 visit

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02688647


Locations
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United States, Arizona
Pulmonary Associates, PA
Phoenix, Arizona, United States, 85006
University of Arizona
Tucson, Arizona, United States, 85724
United States, California
UC Davis Medical Center, Division of Pulmonary/CC/SM
Sacramento, California, United States, 95817
United States, Florida
St. Francis Medical Institute
Clearwater, Florida, United States, 33765
Pulmonary Disease Specialists, PA, d/b/a PDS Research
Kissimmee, Florida, United States, 34741
Central Florida Pulmonary Group, PA
Orlando, Florida, United States, 32803
United States, Georgia
Piedmont Healthcare Pulmonary and Critical Care Research
Austell, Georgia, United States, 30106
United States, North Carolina
Pulmonix, LLC
Greensboro, North Carolina, United States, 27403
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Kadmon Corporation, LLC
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Responsible Party: Kadmon Corporation, LLC
ClinicalTrials.gov Identifier: NCT02688647    
Other Study ID Numbers: KD025-207
First Posted: February 23, 2016    Key Record Dates
Last Update Posted: March 9, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kadmon Corporation, LLC:
Pulmonary Fibrosis
Fibrosis
Idiopathic Interstitial Pneumonias
Lung Diseases
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial