Early Signs of Efficacy Study With Riociguat in Adult Homozygous Delta F508 Cystic Fibrosis Patients

Bayer

Status and phase: Terminated; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Riociguat (Adempas, BAY63-2521); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02170025

17020

2013-004595-35 (EudraCT Number)

Details and patient eligibility

About

Assessment of the safety, tolerability and early signs of efficacy of three times a day orally administered BAY63-2521 in adult delta F508 homozygous Cystic Fibrosis patients not on treatment with Orkambi

Full description

The study consists of two parts. The first part is double-blind, randomized and placebo-controlled. The second part has an open-label study design. In part 1 patients on Orkambi or other CFTR-modulators are excluded. In part 2 patients on Orkambi are allowed to be included under certain conditions.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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21 participants in 2 patient groups

Riociguat (Adempas, BAY63-2521)

Experimental group

Description:

Participants received 0.5 mg BAY63-2521 three times daily (tid) for 14 days. The dose would be increased to 1 mg BAY63-2521 for an additional 14 days, if this was considered safe and tolerable on the basis of the available data for a given patient.

Treatment:

Drug: Riociguat (Adempas, BAY63-2521)

Placebo

Experimental group

Description:

Participants received matching placebo tid.

Treatment:

Drug: Placebo