Ensayos clínicos

Inclusion Criteria:

• Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
• Is between the ages of 18 and 80 years, inclusive.
• Has had RCC (including unexplained chronic cough) for at least 1 year prior to screening, defined as follows:
  • insufficient improvement in cough after treatment for the underlying condition causing the cough; OR
  • unexplained cough for which an underlying condition has not been determined.
• Has had a chest radiograph or CT thorax within the 5 years before screening and following the onset of chronic cough that does not show any abnormality considered to be significantly contributing to the chronic cough, as per the investigator opinion.
• Has an awake cough frequency of ≥25 coughs/hour at screening and at Day –6. For the low-cough cohort, awake cough frequency of ≥ 10 to < 25 coughs/hour at screening and at Day -6.
• Has a score of ≥4 0 mm on the Cough Severity VAS at screening and at Day 1.
• If a woman of childbearing potential has a negative serum β-HCG pregnancy test conducted during screening.
• Highly effective methods of birth control in this study include:
  • combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation;
  • intrauterine device;
  • intrauterine hormone-releasing system;
  • bilateral tubal occlusion;
  • vasectomized partner.
• If a male, agrees to make no donation of sperm from screening until 3 months after the last dose of study treatment and agrees to use condoms during intercourse from screening to the follow-up visit.

Exclusion Criteria:

• Female participants who are pregnant, trying to become pregnant, or lactating.
• Current smoker/vaper or current use of the following inhaled substances (e.g., tobacco or cannabis smoke, nicotine vapors).
• Individuals who have given up smoking or vaping within the past 6 months, or those with a > 20 pack-year smoking history.
• Diagnosis of COPD, bronchiectasis, or idiopathic pulmonary fibrosis based on clinician assessment.
• Uncontrolled asthma defined as one or both of the following:
  • ≥ 1 exacerbation in the last 6 months or ≥ 2 exacerbations in the last 12 months;
  • Use of rescue medication ≥ 3 days per week or night waking >1 time per week (Pre-exercise prophylactic medication use will not be considered rescue medication).
• Pre-bronchodilator FEV1/FVC <60% at screening or on spirometry testing performed within the 2 years before screening and following the onset of chronic cough.
• Participants who fail to use the cough monitor or who are confirmed to have incorrectly recorded 24-hour cough frequency at screening or baseline visits.
  • Note: A single retest will be allowed for the purpose of eligibility at screening or Day -6 in the event that insufficient recording time is captured to assess cough frequency. If insufficient time is recorded at baseline, a retest may be performed only if retesting will occur within the protocol-defined window for the Day -6 visit. Incorrectly recorded 24-hour cough frequencies are defined as recordings where less than 20 hours of the recording can be assessed for cough frequency. 
• History of upper and/or lower respiratory tract infection or recent significant change in pulmonary status within 28 days of screening.
• Current active tuberculosis or nontuberculous mycobacterial infection, a history of latent untreated tuberculosis, or a history of incompletely treated tuberculosis.
• Laboratory-confirmed SARS-CoV-2 infection at screening or Day -6.
• History of SARS-CoV-2 infection or COVID-19 within 3 months of screening or known exposure to someone with SARS-CoV-2 infection or COVID-19 within 1 month of screening.
• Medical history of hypogeusia/dysgeusia/ageusia or known presence of a dysfunction in the ability to taste, including loss of taste secondary to SARS-CoV-2 infection.
• Screening SBP > 160 mm Hg or a DBP > 90 mm Hg.
• Clinically significant abnormal ECG at screening, per investigator discretion.
• Prolonged corrected QT (QTcF) interval (Men: > 450 ms; Women: > 470 ms) at screening.
• Clinically significant abnormal laboratory tests at screening, including the following:
  • Alkaline phosphatase, ALT/SGPT, AST/SGOT > 1.50 × the ULN;
  • GGT > 2.0 × ULN;
  • Total bilirubin above ULN;
  • Creatinine > 2.0 × ULN;
  • Unexplained creatine kinase concentration > 3 × ULN, per investigator discretion;
  • Hemoglobin < 10 g/dL, WBC count < 2500 mm^3;
  • Neutrophil count < 1500 mm^3;
  • Platelet count < 100 × 10^3/mm^3.
  • Note: One repeat laboratory test may be permitted following discussion with the medical monitor.
  • Note: Participants with neutrophil count >1000 mm^3 and a diagnosis of benign ethnic neutropenia will be eligible.
• Positive serological test for HIV, hepatitis B (hepatitis B surface antigen), or hepatitis C.
  • Note: Participants with positive hepatitis B or C serology will have confirmatory testing with hepatitis B or C RNA PCR.
• Acutely ill or febrile 24 hours prior to or at the screening visit. Fever is defined as a body temperature ≥ 38.0°C/100.4°F.
• Medical history of malignancy ≤ years prior to screening, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, in the opinion of the investigator.
• History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years, per investigator assessment or a positive urine drug result at screening. If urine drug screen at screening is positive for cannabinoids the patient should be asked about route of administration, as smoking is an exclusion criterion however oral use is acceptable.
• Has a known allergy/sensitivity or contraindication to BLU-5937 or any of its excipients.
• Previous participation in an investigational study of BLU-5937.
• Any current usage of biologics. Previous use that ended > 90 days prior to screening may be allowed if approved by the medical monitor.
• Treatment with any other investigational products within the 3 months before first dose of study treatment.
• Participants who are considered ineligible to participate in the study for any other reason, based on the investigator’s judgment.
• Noncompliance (< 80%) with single-blind, placebo, run-in medication up to Day 1.