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

NCT02170025 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 170202013-004595-35
• Study Type: interventional
• Target: 21
• Locations: 7 countries
• Sites: 10

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

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; delta F508; Safety; Tolerability; Sweat Chloride; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Change of Sweat Chloride Content From Baseline

  Sweat chloride samples were obtained by using a Macroduct induction and collection device according to standard procedures.

  Baseline, at day 14 and day 28 in study part 1

Secondary Outcomes (1)

• Change of FEV1 From Baseline

  From Baseline to Day 14, Day 28 and Follow-up

Study Arms (2)

Riociguat (Adempas, BAY63-2521)

EXPERIMENTAL

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.

Drug: Riociguat (Adempas, BAY63-2521)

Placebo

EXPERIMENTAL

Participants received matching placebo tid.

Drug: Placebo

Interventions

Riociguat (Adempas, BAY63-2521) 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.

Riociguat (Adempas, BAY63-2521)

Placebo DRUG

Participants received matching placebo tid.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent available before any study specific tests or procedures are performed
• 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 \[kg/ m2\])
• \- 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)

You may not qualify if:

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

Sponsors & Collaborators

• Bayer: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Unknown Facility

Birmingham, Alabama, 35233-1711, United States

Location

Unknown Facility

Denver, Colorado, 80206, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Bruxelles - Brussel, 1090, Belgium

Location

Unknown Facility

Toronto, Ontario, M5B 1W8, Canada

Location

Unknown Facility

Paris, 75674, France

Location

Unknown Facility

Berlin, 13353, Germany

Location

Unknown Facility

Rotterdam, 3015 CE, Netherlands

Location

Unknown Facility

Belfast, North Ireland, BT12 7AB, United Kingdom

Location

Unknown Facility

London, SW3 6NP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34419414 RESULT

Related Links

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

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

riociguat

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

Based on multiple factors, the design of part 2 is no longer appropriate. Study was terminated at the end of part 1. No safety concerns were identified.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayer.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 23, 2014
• Study Start: September 30, 2014
• Primary Completion: January 17, 2017
• Study Completion: September 22, 2017
• Last Updated: November 7, 2023
• Results First Posted: March 29, 2018

Record last verified: 2023-11

Locations

GB (2); BE (1); US (3); CA (1); DE (1); FR (1); NL (1)