Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

NCT02871778 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: PS-G2022015-004917-26
• Study Type: interventional
• Target: 123
• Locations: 8 countries
• Sites: 34

Brief Summary

To evaluate the safety and efficacy of treatment with VX-371 with and without ivacaftor, and the effect of VX-371 with and without ivacaftor on quality of life (QOL) in subjects with primary ciliary dyskinesia (PCD).

Conditions

Primary Ciliary Dyskinesia

Outcome Measures

Primary Outcomes (5)

• Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 84 days that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.

  Part A: From first dose of study drug up 84 days

• Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.

  Part B: Day 85 up to 28 days after last dose of study drug (56 days)

• Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

  Part A: Study Baseline, Day 29 of each treatment period

• Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

  Study Baseline, Day 29 of Part B

• Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.

  Part B Baseline, Day 29 of Part B

Secondary Outcomes (6)

• Part A: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29

  Study Baseline, Day 29 of Part A

• Part B: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29

  Study Baseline, Day 29 of Part B

• Part B: Change From Part B Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29

  Part B Baseline, Day 29 of Part B

• Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged Greater Than or Equals to (>=) 16 Years at Day 29

  Study Baseline, Day 29 of Part A

• Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29

  Study Baseline, Day 29 of Part B

Study Arms (8)

Part A: VX-371 in Hypertonic Saline (HS), Then HS

EXPERIMENTAL

Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS twice daily through oral nebulized inhalation from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.

Drug: Hypertonic Saline; Drug: VX-371 + HS

Part A: HS, Then VX-371 in HS

EXPERIMENTAL

Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.

Drug: Hypertonic Saline; Drug: VX-371 + HS

Part A: VX-371, Then Placebo

EXPERIMENTAL

Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.

Drug: VX-371; Drug: Placebo (0.17% saline)

Part A: Placebo, Then VX-371

EXPERIMENTAL

Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.

Drug: VX-371; Drug: Placebo (0.17% saline)

Part B: VX-371 in HS + Ivacaftor

EXPERIMENTAL

Participants who were on 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.

Drug: VX-371 + HS; Drug: Ivacaftor

Part B: HS + Ivacaftor

EXPERIMENTAL

Participants who were on 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.

Drug: Hypertonic Saline; Drug: Ivacaftor

Part B: VX-371 + Ivacaftor

EXPERIMENTAL

Participants who were on 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.

Drug: VX-371; Drug: Ivacaftor

Part B: Placebo + Ivacaftor

PLACEBO COMPARATOR

Participants who were on 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.

Drug: Placebo (0.17% saline); Drug: Ivacaftor

Interventions

VX-371 DRUG

Part A: Placebo, Then VX-371; Part A: VX-371, Then Placebo; Part B: VX-371 + Ivacaftor

Hypertonic Saline DRUG

Part A: HS, Then VX-371 in HS; Part A: VX-371 in Hypertonic Saline (HS), Then HS; Part B: HS + Ivacaftor

Placebo (0.17% saline) DRUG

Part A: Placebo, Then VX-371; Part A: VX-371, Then Placebo; Part B: Placebo + Ivacaftor

VX-371 + HS DRUG

Part A: HS, Then VX-371 in HS; Part A: VX-371 in Hypertonic Saline (HS), Then HS; Part B: VX-371 in HS + Ivacaftor

Ivacaftor DRUG

Part B: HS + Ivacaftor; Part B: Placebo + Ivacaftor; Part B: VX-371 + Ivacaftor; Part B: VX-371 in HS + Ivacaftor

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must have evidence supportive of a PCD diagnosis.
• Subjects with percent predicted FEV1 of ≥40 to \<90 percentage points
• Non-smoker for at least 90 days prior to the Screening Visit and less than a 5 pack-year lifetime history of smoking
• Stable regimen of medications and chest physiotherapy for the 28 days prior to Day 1
• If currently using daily inhaled HS, must be able to discontinue its use for the duration of the study.
• If taking daily chronic or chronic cycling antibiotics, has been on a consistent regimen for at least 4 months prior to the Screening Visit.
• Clinically stable (as deemed by the investigator) for at least 14 days prior to the Screening Visit
• Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit. Subjects of childbearing potential and who are sexually active must meet the contraception requirements.

You may not qualify if:

• Diagnosis of CF based on results of sweat chloride or nasal potential difference (NPD) tests or presence of 2 CF-causing mutations in CFTR gene.
• History of any organ transplantation or lung resection or chest wall surgery.
• Significant congenital heart defects, other than a laterality defect, at the discretion of the investigator
• Diagnosis of Cri du chat syndrome (chromosome 5p deletion syndrome).
• Inability to withhold short-acting bronchodilator use for 4 hours prior to clinic visit and long-acting bronchodilator use the night before the first and last clinic visit of each treatment period.
• Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs
• Symptoms of acute upper or lower respiratory tract infection, acute pulmonary exacerbation, or treatment or was treated with systemic antibiotics for ear or sinus disease within 28 days before Day 1 (topical otic antibiotics allowed).
• History of significant intolerance to inhaled HS
• Pregnant and/or nursing females
• Any clinically significant laboratory abnormalities
• History of chronic B. cepacia complex or M. abscessus or M. avium
• Surgery that required general anesthesia and hospitalization within 3 months of Day 1
• Unable to swallow tablets.
• Concomitant use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications (e.g., St. John's Wort), and grapefruit/grapefruit juice.
• Known hypersensitivity to ivacaftor.

Sponsors & Collaborators

• Parion Sciences: lead
• Vertex Pharmaceuticals Incorporated: collaborator

Study Sites (34)

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Birmingham, Alabama, United States

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Palo Alto, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Miami, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Kansas City, Kansas, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Cleveland, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Columbia, South Carolina, United States

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Seattle, Washington, United States

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Copenhagen, Denmark

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Münster, North Rhine-Westphalia, Germany

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Hanover, Germany

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Heidelberg, Germany

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Pisa, Italy

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Amsterdam, Netherlands

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Rotterdam, Netherlands

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Rabka-Zdrój, Poland

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Cambridge, United Kingdom

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London, United Kingdom

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Southampton, United Kingdom

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Related Publications (1)

• Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team. Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. Lancet Respir Med. 2024 Jan;12(1):21-33. doi: 10.1016/S2213-2600(23)00226-6. Epub 2023 Aug 31.

  PMID: 37660715 DERIVED

MeSH Terms

Conditions

Ciliary Motility Disorders

Interventions

Saline Solution, Hypertonic; Sodium Chloride; ivacaftor

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Karl Donn
• Organization: Parion Sciences

kdonn@parion.com

919 313 1185

Study Officials

• Karl Donn

  Parion Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: August 18, 2016
• Study Start: August 1, 2016
• Primary Completion: November 20, 2018
• Study Completion: November 20, 2018
• Last Updated: December 16, 2021
• Results First Posted: December 16, 2021

Record last verified: 2021-11

Locations

US (21); CA (2); DE (3); NL (2); IT (1); GB (3); PL (1); DK (1)