Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Sacramento, California and other locations
Dates
study started
completion

Description

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

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)

Details

This is a Phase 2, randomized, open-label, multicenter study in subjects with IPF who had either received pirfenidone and/or nintedanib or had been offered both treatments. Approximately 81 eligible subjects with IPF will be randomly enrolled in a 2:1 ratio (KD025 to BSC) to 1 of 2 treatment groups: - Treatment Group 1 (Experimental): Receive KD025 400 mg orally QD for 24 weeks - Treatment Group 2 (Control): Receive BSC, deemed appropriate by the Investigator, for 24 weeks Screening Period: The Screening Period is up to 29 days prior to entry into the study. Treatment Period: After the Screening Visit, subjects will visit the site at Baseline (Week 1 Day 1), and the end of Weeks 4, 8, 12, 16, 20, and 24 (± 3 days). Subjects in Treatment Group 1 will receive their first dose of KD025 in the clinic on Week 1 Day 1. KD025 will then be dispensed for home administration. Subjects in Treatment Group 1 who complete 24 weeks of treatment with KD025 400 mg QD will have the option of continuing therapy with KD025 400 mg QD up to an additional 72 weeks if there are no safety signals and if clinical progress continues. No subject in Treatment Group 1 is permitted to receive therapy with KD025 greater than a total of 96 weeks. Subjects in Treatment Group 2 who complete 24 weeks of BSC will have the option of crossing over to therapy with KD025 400 mg QD for up to 96 weeks if there are no safety signals and if clinical progress continues. No subject in Treatment Group 2 is permitted to receive KD025 400 mg QD therapy greater than 96 weeks. All subjects will undergo the same assessments. Efficacy assessments include: - Pulmonary Function Tests (PFTs), which include FVC; residual volume (RV); and diffusing capacity of the lungs for carbon monoxide [DLCO]); - Six-minute walking distance (6MWD); - Frequency and severity of IPF exacerbation; - Time to acute exacerbation of IPF; - High-resolution computed tomography (HRCT); - St. George's Respiratory Questionnaire (SGRQ) Safety assessments include: - Adverse events (AEs); - Serious adverse events (SAEs); - Physical examinations (PEs); - Vital sign (VS) measurements; - Clinical laboratory evaluations (hematology, chemistry, and urinalysis), - Electrocardiograms (ECGs); - Reasons for treatment discontinuation due to toxicity. Exploratory assessments include biomarkers: - Matrix Metalloproteinase-7 (MMP7); - Chemokine Ligand 18 (CCL18); - Surfactant Protein-D (SPD). Follow-up Period: Follow-up Visits will occur 30 days (± 3 days) after the last dose of KD025. (A Follow-up Visit is not necessary for subjects receiving BSC.) Subjects will undergo the following safety assessments: complete PEs, VS measurements, weight measurements, AE assessments, concomitant medication and procedures assessments, blood sample collection for hematology (including coagulation), chemistry and thyroid function (TSH), pulmonary function tests (PFTs), and urinalysis. If another therapy is started within 30 days after the last dose of study drug, the Follow-up visit will be conducted before the start of the other therapy. Duration of Treatment: Treatment Group 1: Subjects will receive KD025 400 mg QD for 24 weeks. After 24 weeks of therapy, subjects will have the option of continuing therapy with KD025 400 mg QD. Subjects who do not continue KD025 400 mg QD after 24 weeks will remain on study up to a total of 32 weeks: 4 weeks for screening, 24 weeks of treatment with KD025 400 mg QD, and 4 weeks of Follow-up. Subjects who chose to continue therapy with KD025 400 mg QD after 24 weeks will be permitted to remain on-study up to a total of 104 weeks: a 4-week screening, 96-week treatment period with KD025 400 mg QD (an initial 24-week period and an additional 72-week period), and a 4-week Follow-up. No subject will be permitted to receive more than 96 weeks of treatment with KD025 400 mg QD. Treatment Group 2: Subjects will receive BSC for 24 weeks, after which they will have the option to cross over to treatment with KD025 400 mg QD. Subjects who do not cross over will remained on-study up to 32 weeks: 4-week screening, 24-week BSC, and 4-week Follow-up. Subjects who chose to crossover to KD025 400 mg QD therapy therapy are permitted to remain on-study up to 128 weeks: 4-week screening, 24-week BSC, 96-week treatment with KD025 400 mg QD, and 4-week Follow-up. No subject will be permitted to receive more than 96 weeks of treatment with KD025 400 mg QD.

Keywords

Idiopathic Pulmonary Fibrosis Pulmonary Fibrosis Fibrosis Idiopathic Interstitial Pneumonias Lung Diseases BSC KD025 400 mg Daily

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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:
  • Absolute neutrophil count > 1500/mm3

  • Hemoglobin > 9.0 g/L
  • Platelets > 100,000/mm3

  • 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.

You CAN'T join if...

  • 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:
  • Immunosuppressive or cytotoxic drugs including cyclophosphamide and azathioprine
  • Antifibrotic drugs including pirfenidone, nintedanib, D-penicillamine, colchicine, tumor necrosis factor-alpha blockers, imatinib, and interferon-γ
  • Chronic use of N-acetylcysteine prescribed for IPF (> 600 mg/day)
  • 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

Locations

  • UC Davis Medical Center, Division of Pulmonary/CC/SM
    Sacramento California 95817 United States
  • Pulmonary Associates, PA
    Phoenix Arizona 85006 United States

Details

Status
accepting new patients
Start Date
Completion Date
Sponsor
Kadmon Corporation, LLC
Links
Sign up for this study
ID
NCT02688647
Phase
Phase 2
Study Type
Interventional
Last Updated