A Clinical Study to Test How Effective and Safe GLPG1205 is for Participants With Idiopathic Pulmonary Fibrosis (IPF) (PINTA)

• ClinicalTrials.gov Identifier: NCT03725852
• Recruitment Status: Completed
• First Posted: October 31, 2018
• Results First Posted: September 14, 2021
• Last Update Posted: September 14, 2021
• Sponsor: Galapagos NV
• Information provided by (Responsible Party): Galapagos NV

Tracking Information

• First Submitted Date: June 8, 2018
• First Posted Date: October 31, 2018
• Results First Submitted Date: July 14, 2021
• Results First Posted Date: September 14, 2021
• Last Update Posted Date: September 14, 2021
• Actual Study Start Date: September 27, 2018
• Actual Primary Completion Date: July 21, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 18, 2021)

Change From Baseline in Forced Vital Capacity (FVC) at Week 26 [ Time Frame: Baseline, Week 26 ]

Forced vital capacity (FVC) (in milliliter [mL]) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.

Original Primary Outcome Measures (submitted: October 29, 2018)

Change from baseline in forced vital capacity (FVC) (mL) over 26 weeks compared to placebo. [ Time Frame: From Day 1 to Week 26 ]

To evaluate the efficacy of GLPG1205 treatment in subjects with IPF on pulmonary function as evaluated by FVC compared to placebo over 26 weeks.

Current Secondary Outcome Measures (submitted: August 18, 2021)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Related to Study Drug, and TEAEs Leading to Study Drug Discontinuation [ Time Frame: First dose date up to 30 days after the last dose of study drug (maximum up to 263 days) ]
  An adverse event (AE) was any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with study drug. A TEAE was any AE with an onset date on or after the start of study drug intake and no later than 30 days after last dose of study drug, or any worsening of any AE on or after the start of study drug intake. A serious AE was defined as an AE that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was medically significant.
• Time to Any Major Events Depicted by Cumulative Percentage of Participants With All-cause Deaths, Respiratory-related Deaths, All-cause Hospitalizations, and Respiratory-related Hospitalizations [ Time Frame: Day 1 up to Week 30 ]
  Treatment effect on time to death (all-cause and respiratory-related)/hospitalization (all-cause and respiratory-related) were assessed using the log-rank test. Kaplan-Meier estimates were derived for the probability of death (all-cause and respiratory-related)/hospitalization (all-cause and respiratory-related). Cumulative percentage of participants with all-cause deaths, respiratory-related deaths, all-cause hospitalizations, and respiratory-related hospitalizations were reported.
• Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 26 [ Time Frame: Baseline, Week 26 ]
  The 6-MWT depicts the total distance covered by a participant during 6 minutes of walking.
• Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 26 [ Time Frame: Baseline, Week 26 ]
  The SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being, split into 3 domains: symptoms (assessing the frequency and severity of respiratory symptoms), activity (assessing the effects of breathlessness on mobility and physical activity), and impact (assessing the psychosocial impact of the disease). Scores were weighted such that each domain score and the total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL.
• Change From Baseline in SGRQ Domain Score at Week 26 [ Time Frame: Baseline, Week 26 ]
  The SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related QOL and well-being, split into 3 domains: symptoms (assessing the frequency and severity of respiratory symptoms), activity (assessing the effects of breathlessness on mobility and physical activity), and impact (assessing the psychosocial impact of the disease). Scores were weighted such that each domain score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL.
• Percentage of SGRQ Responders [ Time Frame: Baseline up to Week 26 ]
  The SGRQ is a 50-item paper questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related QOL and well-being, split into 3 domains: symptoms (assessing the frequency and severity of respiratory symptoms), activity (assessing the effects of breathlessness on mobility and physical activity), and impact (assessing the psychosocial impact of the disease). Scores were weighted such that each domain score and total score ranged from 0 to 100, with higher scores indicating the poorer health-related QOL. SGRQ responders are those with absolute change from baseline in SGRQ total score less than or equal to -4 percent (%) at least once.
• Pre-dose Plasma Concentration (Ctrough) of GLPG1205 at Week 26 [ Time Frame: Week 26 (pre-dose) ]
  GLPG1205 pre-dose plasma concentration (Ctrough) at Week 26 was reported applying the exclusion rules (e.g. dose reduction, discontinuation, samples flagged).
• Pre-dose Plasma Concentration (Ctrough) of Nintedanib at Week 20 [ Time Frame: Week 20 (pre-dose) ]
  Nintedanib pre-dose plasma concentration (Ctrough) at Week 20 was reported applying the exclusion rules (e.g. dose reduction, discontinuation, samples flagged).
• Pre-dose Plasma Concentration (Ctrough) of Pirfenidone at Week 20 [ Time Frame: Week 20 (pre-dose) ]
  Pirfenidone pre-dose plasma concentration (Ctrough) at Week 20 was reported applying the exclusion rules (e.g. dose reduction, discontinuation, samples flagged).

Original Secondary Outcome Measures (submitted: October 29, 2018)

• The number of incidents of Treatment-Emergent Adverse Events (TEAEs), Unlisted (Unexpected) Adverse Events, Serious Adverse Events (SAEs), and discontinuations due to Adverse Events (AEs). [ Time Frame: From Day 1 to Week 26 ]
  To evaluate the safety and tolerability of GLPG1205 treatment compared to placebo over 26 weeks.
• Time to any of major events (whichever occurs first) defined as below: [ Time Frame: From Day 1 through study completion up to Week 30 ]
  To evaluate the impact of GLPG1205 treatment compared to placebo on time to any major events (whichever occurs first) defined as:

  • Respiratory-related mortality
  • Hospitalization (all-cause and respiratory related)
  • Need for placement on a lung transplant list
• Change from baseline in functional exercise capacity, assessed by the six-minute walk test (6MWT) at Week 26. [ Time Frame: From Day 1 to Week 26 ]
  To evaluate the changes from baseline in functional exercise capacity measured by the 6MWT, in IPF subjects treated with GLPG1205 compared to placebo at Week 26.
• Change from baseline until 26 weeks in quality of life measures, assessed by the St.George's Respiratory Questionnaire (SGRQ) total score and domains and proportion of SGRQ responders. [ Time Frame: From Day 1 to Week 26 ]
  To evaluate the changes in quality of life measures in IPF subjects treated with GLPG1205 compared to placebo over 26 weeks.
• Concentrations of GLPG1205, nintedanib and pirfenidone. [ Time Frame: From Day 1 to Week 30 ]
  To evaluate the pharmacokinetics (PK) of GLPG1205, nintedanib and pirfenidone in IPF subjects.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Clinical Study to Test How Effective and Safe GLPG1205 is for Participants With Idiopathic Pulmonary Fibrosis (IPF)
• Official Title: A Phase II Randomized, Double-blind, Placebo-controlled, 26-week Study to Evaluate the Efficacy, Safety and Tolerability of GLPG1205 in Subjects With Idiopathic Pulmonary Fibrosis
• Brief Summary: This is a randomized, double-blind, parallel-group, placebo-controlled, multicenter, exploratory Phase 2 study including participants with Idiopathic Pulmonary Fibrosis (IPF), investigating GLPG1205 in addition to the local standard of care (defined as receiving nintedanib, pirfenidone, or neither nintedanib nor pirfenidone).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Idiopathic Pulmonary Fibrosis

Intervention

• Drug: GLPG1205
  GLPG1205 will be provided as an oral hard gelatin capsule.
• Drug: Placebo
  GLPG1205 matching placebo will be provided as an oral hard gelatin capsule.

Study Arms

• Experimental: GLPG1205 100 mg
  Participants will receive GLPG1205 100 milligrams (mg) (2 capsules x 50 mg), orally once daily for 26 weeks in addition to the local standard of care. Standard of care includes nintedanib, pirfenidone, or neither nintedanib nor pirfenidone.
  Intervention: Drug: GLPG1205
• Placebo Comparator: Placebo
  Participants will receive GLPG1205 matching placebo, orally once daily (as 2 capsules) for 26 weeks in addition to the local standard of care. Standard of care includes nintedanib, pirfenidone, or neither nintedanib nor pirfenidone.
  Intervention: Drug: Placebo

• Publications *: Strambu IR, Fagard L, Ford P, Van Der Aa T, De Haas-Amatsaleh A, Santermans E, Seemayer C. (2020). Idiopathic pulmonary fibrosis (IPF): observations from a Phase 2 trial of GLPG1205 (PINTA). Abstract for European Respiratory Society International Congress 7-9 September 2020.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 18, 2021): 68
• Original Estimated Enrollment (submitted: October 29, 2018): 60
• Actual Study Completion Date: August 14, 2020
• Actual Primary Completion Date: July 21, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

Participants who meet all of the following criteria are eligible for the study:

• A diagnosis of IPF within 5 years prior to the screening visit as per applicable American Thoracic Society (ATS)/European Respiratory Society(ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guideline. Participants receiving local standard of care for the treatment of IPF, defined as either pirfenidone or nintedanib at a stable dose for at least 8 weeks before screening, and during screening; or neither pirfenidone nor nintedanib (for any reason). A stable dose is defined as the highest tolerated dose. Prednisone at steady dose less than or equal to 10 mg/day or equivalent glucocorticoid dose is allowed (stabilized 4 weeks prior to screening and continued without variation of dose or regimen). Supportive care like supplemental oxygen or pulmonary rehabilitation is allowed.

• Meeting all of the following criteria at screening and during the screening period:

  • Forced vital capacity (FVC) greater than or equal to 50% predicted of normal
  • Disease progression, defined as a decline of FVC (% predicted or milliliters [mL]) at the investigator's discretion, during the 9 months prior to the screening period and confirmed at the screening visit
  • Diffusing capacity for the lungs for carbon monoxide (DLCO) greater than or equal to 30% predicted of normal (corrected for hemoglobin)
  • Ratio of forced expiratory volume in one second (FEV1) to FVC greater than or equal to 0.70
• In a stable condition and suitable for study participation based on the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and laboratory evaluation. Stable condition is based on the clinical judgment of the investigator, co-morbidities should be treated according to the local applicable guidelines. Concomitant medication for chronic comorbidities should be stabilized from 4 weeks before screening and during the screening period (stable defined as no clinically relevant change according to the investigator's judgement).
• Able to walk at least 150 meters during the 6 Minute Walk Test (6MWT) at screening; without having a contraindication to perform the 6MWT.

This list only describes the key inclusion criteria.

Exclusion criteria:

Participants meeting one or more of the following criteria cannot be selected for this study:

• Known hypersensitivity to any of the investigational medicinal product (IMP) ingredients or a history of a significant allergic reaction to any drug as determined by the investigator (e.g. anaphylaxis requiring hospitalization).
• Current immunosuppressive condition (e.g. human immunodeficiency virus [HIV] infection, congenital, acquired, medication induced, organ transplantation).
• Positive blood testing for hepatitis B surface antigen (HBS Ag) or hepatitis C virus (HCV) antibody (if positive, confirmed by HCV ribonucleic acid [RNA] positivity). Note: Participants with a resolved hepatitis A at least 3 months prior to first dosing of the IMP can be included.
• History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, and prostate cancer medically managed through active surveillance or watchful waiting, and squamous cell carcinoma of the skin if fully resected).
• Acute IPF exacerbation within 3 months prior to screening and during the screening period.
• Lower respiratory tract infection requiring antibiotics within 4 weeks prior to screening and/or during the screening period.
• Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis, amyloidosis), exposures (e.g. radiation, silica, asbestos, coal dust), and drugs (e.g. amiodarone).
• History of lung volume reduction surgery or lung transplant.
• Unstable cardiovascular, pulmonary (other than IPF) or other disease within 6 months prior to screening or during the screening period (e.g. coronary heart disease, heart failure, stroke).
• Participant participating in a drug, device or biologic investigational research study, concurrently with the current study, within 12 weeks or 5-half-lives of the agent, whichever is longer, prior to screening, or prior participation in an investigational drug antibody/biologic study within 6 months prior to screening.

This list only describes the key exclusion criteria.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Croatia, Finland, France, Oman, Romania, Slovakia, Sweden, Ukraine

Administrative Information

• NCT Number: NCT03725852
• Other Study ID Numbers: GLPG1205-CL-220; 2017-004302-18 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Galapagos NV
• Original Responsible Party: Same as current
• Current Study Sponsor: Galapagos NV
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Christian Seemayer, MD; Galapagos NV

• PRS Account: Galapagos NV
• Verification Date: August 2021