Clinical trial: Early Signs of Efficacy Study With Riociguat in Adult Homozygous Delta F508 Cystic Fibrosis Patients (NCT02170025)

Eligibility criteria:
Inclusion Criteria:

          -  Signed informed consent available before any study specific tests or procedures are
             performed

          -  Patients must be at least 18 years of age at time of inclusion (i.e. upon signature of
             informed consent)

          -  Patient diagnosed with Cystic Fibrosis according to standard criteria (i.e. either
             elevated sweat chloride content above 60 mmol/ L and/ or genetic testing)

          -  Patient is homozygous for the deltaF508 mutation

          -  Patient has a mild-to-moderate stage of lung disease as determined by FEV1 (FEV1
             between 40 and 100% predicted)

          -  Patient has a stable condition of lung disease (no ongoing or recent pulmonary
             exacerbation and no change in current treatment) within the last 4 weeks prior to
             screening

          -  Ability and willingness to understand and follow study procedures for the entire study

          -  Patients do not smoke. Patients with a history of smoking can be included, if they
             have refrained from smoking for the last 3 months. If a patients starts smoking during
             the study participation, he/ she needs to be excluded and considered to be a drop out

          -  Body mass index (BMI): ≥ 16 kg/ m² (calculated by dividing the patient's weight by the
             square of his/ her height [kg/ m2])

        Inclusion criterion valid for study part 1 only:

        - Women of childbearing potential must agree to use adequate contraception when sexually
        active. 'Adequate contraception' is defined as one highly effective form of contraception
        (intrauterine devices [IUD], contraceptive implants or tubal sterilization) or a
        combination of methods (hormone method with a barrier method ). If a partner's vasectomy is
        the chosen method of contraception or if a partner has documented azoospermia, a hormone or
        barrier method must be used in combination. Adequate contraception is required from the
        signing of the informed consent form up until 4 weeks after the last study drug
        administration

        Inclusion criteria valid for study part 2 only:

          -  Women of childbearing potential must agree to use adequate contraception when sexually
             active. 'Adequate contraception' is defined as one highly effective form of
             contraception (intrauterine devices [IUD], contraceptive implants or tubal
             sterilization) or a combination of methods (hormone method with a barrier method). For
             patients on Orkambi hormonal methods (including hormonal oral contraceptives) cannot
             be accepted in this study. They need to choose non-hormonal methods. If a partner's
             vasectomy is the chosen method of contraception or if a partner has documented
             azoospermia, a hormone or barrier method must be used in combination. Adequate
             contraception is required from the signing of the informed consent form up until 4
             weeks after the last study drug administration

          -  Patients receiving Orkambi (Lumcaftor + Ivacaftor) as part of their standard care need
             to be on stable Orkambi treatment for at least 3 months prior to screening (patients
             on Lumacaftor and/or Ivacaftor are excluded in part 1)

        Exclusion Criteria:

          -  Patients with Cystic Fibrosis with any background other than homozygous deltaF508
             mutation

          -  Exclusion criterion only valid for study part 1: Patients receiving treatment with
             Lumacaftor and/ or Ivacaftor

          -  Active state of hemoptysis or pulmonary hemorrhage, including those events managed by
             bronchial artery embolization. Also any history of moderate hemoptysis within the 3
             months prior to inclusion

          -  Any history of pneumothorax, bronchial artery embolization or massive hemoptysis.
             Massive hemoptysis being defined as acute bleeding >240 mL in a 24-hour period or
             recurrent bleeding >100 mL/ d over several days

          -  A positive sputum culture for Burkholderia cenocepacia, Burkholderia dolosa, and/ or
             Mycobacterium abscessus either currently or within the previous year

          -  Active allergic broncho-pulmonary aspergillosis

          -  Current pulmonary exacerbation

          -  Known history of solid organ transplantation

          -  Known history of any form of pulmonary hypertension

          -  Clinically relevant deviations of the screened laboratory parameters from reference
             ranges outside of expected changes for Cystic Fibrosis patients, especially a
             hemoglobin value below 110 g/L or a creatinine clearance based on the Cockcroft-Gault
             formula < 15 ml/ min
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient description (patient's own words): I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Does the patient match the trial criteria? Entailment