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

NCT ID: NCT02170025

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2017-09-22

Brief Summary

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

Detailed 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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Riociguat (Adempas, BAY63-2521)

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.

Group Type: EXPERIMENTAL

Riociguat (Adempas, BAY63-2521)

Intervention Type: DRUG

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.

Placebo

Participants received matching placebo tid.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Participants received matching placebo tid.

Interventions

Riociguat (Adempas, BAY63-2521)

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.

Intervention Type: DRUG

Placebo

Participants received matching placebo tid.

Intervention Type: DRUG

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Birmingham, Alabama, United States

Denver, Colorado, United States

St Louis, Missouri, United States

Bruxelles - Brussel, , Belgium

Toronto, Ontario, Canada

Paris, , France

Berlin, , Germany

Rotterdam, , Netherlands

Belfast, North Ireland, United Kingdom

London, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Netherlands; United Kingdom

References

Derichs N, Taylor-Cousar JL, Davies JC, Fajac I, Tullis E, Nazareth D, Downey DG, Rosenbluth D, Malfroot A, Saunders C, Jensen R, Solomon GM, Vermeulen F, Kaiser A, Willmann S, Saleh S, Droebner K, Sandner P, Bear CE, Hoffmann A, Ratjen F, Rowe SM; Rio-CF Study Group. Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis. J Cyst Fibros. 2021 Nov;20(6):1018-1025. doi: 10.1016/j.jcf.2021.07.015. Epub 2021 Aug 19.

Reference Type: RESULT

PMID: 34419414 (View on PubMed)

Related Links

https://clinicaltrials.bayer.com/study/17020

Click here to find further information and, after study completion, the study results according to Bayer's transparency standards

Other Identifiers

2013-004595-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17020

Identifier Type: -

Identifier Source: org_study_id