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

• Status: Completed
• Trial end date: 2021-04-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kadmon Corporation, LLC

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