CTRI/2023/05/052755 [Registered on: 17/05/2023] Trial Registered Prospectively
Last Modified On:
01/04/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A single-arm, open-label study to evaluate the safety and efficacy of FF/UMEC/VI in participants with COPD.
Scientific Title of Study
Phase IV, 12-week, single arm, open label study evaluating the safety and
efficacy of fixed dose triple combination FF/UMEC/VI administered once daily in the
morning via a dry powder inhaler in participants with chronic obstructive pulmonary
disease in India.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
212655 Version no.03,dated 29.11.2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Samir Adsule
Designation
Head of Medical Affairs, Specialty
Affiliation
GSK
Address
GSK
252 , Dr. Annie Besant Road
Worli 400030
Mumbai, India.
Mumbai MAHARASHTRA 400030 India
Phone
Fax
Email
samir.m.adsule@gsk.com
Details of Contact Person Scientific Query
Name
Samir Adsule
Designation
Head of Medical Affairs, Specialty
Affiliation
GSK
Address
GSK
252 , Dr. Annie Besant Road
Worli 400030
Mumbai, India.
Mumbai MAHARASHTRA 400030 India
Phone
Fax
Email
samir.m.adsule@gsk.com
Details of Contact Person Public Query
Name
Samir Adsule
Designation
Head of Medical Affairs, Specialty
Affiliation
GSK
Address
GSK
252 , Dr. Annie Besant Road
Worli 400030
Mumbai, India.
Mumbai MAHARASHTRA 400030 India
Phone
Fax
Email
samir.m.adsule@gsk.com
Source of Monetary or Material Support
GSK,252,Dr. Annie Besant Road
Worli 400030 Mumbai, India.
Primary Sponsor
Name
GSK
Address
252, Dr. Annie Besant Road
Worli 400030
Mumbai, India.
Bhaktivedanta Hospital and Research Institute, Srishti Complex, Bhaktivedanta Swami Marg, Opp ISKON Temple, Mira Road (East) Thane 401107 Maharashtra, India Mumbai MAHARASHTRA
9820452037
drajaygodse.research@gmail.com
Dr Raja Dhar
Calcutta Medical Research Institute
The Calcutta Medical Research Institute 7/2, Diamond Harbour Road, Kolkata 7/2, Diamond Harbour Road, Kolkata Kolkata Kolkata West Bengal 700027. Kolkata WEST BENGAL
9831855512
docaardee@yahoo.com
Dr Santosh Velayudhan
Government Medical College Junction
"17, Mavoor Rd, near Police Station,Kozhikode
Kerala 673008 Kozhikode KERALA
9847105779
drpvsksanam@gmail.com
Dr Piyush Arora
Jawahar Lal Nehru Medical College
Department of Pulmonary Medicine, Jawahar Lal Nehru Medical College, Kala Bagh, Ajmer-305001, Rajasthan
Ajmer RAJASTHAN
Department of Respiratory Medicine, Nil Ratan Sircar Medical College and Hospital, 138, AJC Bose Road, Kolkata-700014, West Bengal. Kolkata WEST BENGAL
FF/UMEC/VI
Dosage Form: ELLIPTA with 30 doses
Frequency: Once daily
Route of Administration: Inhaled
Total duration of intervention: 12 weeks
Comparator Agent
Not Applicable
Single Arm Study.
Inclusion Criteria
Age From
40.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Participants eligible for enrolment in the study must meet all of the following criteria:
1. Informed Consent: A signed and dated written informed consent prior to study
participation.
2. Type of participant: Outpatient.
3. Age: Participants 40 years of age or older at Screening (Visit 1).
4. Gender: Male or female participants.
Female participants:
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP)
OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and until the safety follow-up contact after the last dose of study intervention.
5. COPD Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004].
6. Smoking History: Current or former cigarette smokers with a history of cigarette smoking of more than or equal to 10 pack-years at Screening (Visit 1) (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Previous smokers are defined as those
who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or
cigar use cannot be used to calculate pack-year history.
7. Patient with history of ≥2 moderate exacerbations or one severe (hospitalized)
exacerbation in the previous 12 months, and with a score of ≥10 on the CAT eligible
for the study treatment in the opinion of the investigator and documented post
salbutamol FEV1/FVC ratio of <0.70
8. Existing COPD maintenance treatment: Participant must be receiving daily long acting maintenance treatment for their COPD for at least 3 months prior to Screening.
To be eligible for the study treatment phase, participants must be compliant with their
existing COPD maintenance therapy (in the opinion of the investigator) for the preceding two weeks prior to screening.
Note: Participants receiving only short-acting COPD medications are not eligible.
9. A negative test for active COVID-19 at Visit 1. The test should be done using a molecular (PCR or antigen test) approved by the country regulatory authorities.
ExclusionCriteria
Details
Participants meeting any of the following criteria must not be enrolled in the study:
1. Pregnancy: Women who are pregnant or lactating or are planning on becoming
pregnant during the study.
2. Asthma: Participants with a current diagnosis of asthma. (Participants with a prior
history of asthma are eligible if they have a current diagnosis of COPD).
3. Reversibility: Documented (medical records) evidence of reversibility.
Reversibility is defined as an increase in FEV1 of ≥ 12% and ≥200mL following
administration of salbutamol. Participants defined as non-reversible will have a post-salbutamol increase in FEV1 of <200mL or a ≥200mL increase that is <12% from pre-salbutamol baseline.
4. α1-antitrypsin deficiency: Participants with α1-antitrypsin deficiency as the underlying cause of COPD.
5. Other respiratory disorders: Participants with active tuberculosis, lung cancer, and
clinically significant (in the opinion of the investigator): bronchiectasis, sarcoidosis,
lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active
pulmonary diseases.
6. Lung resection: Participants with lung volume reduction surgery within the 12
months prior to Screening.
7. Risk Factors for Pneumonia: immune suppression (e.g. advanced HIV with high viral load and low CD4 count, Lupus on immuno suppressants that would increase risk of pneumonia) or other risk factors for pneumonia (e.g. neurological disorders
affecting control of the upper airway, such as Parkinson’s Disease, MyastheniaGravis).
Patients at potentially high risk for pneumonia (e.g. very low BMI, severely malnourished, or very low FEV1) will only be included at the discretion of the investigator.
8. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved
at least 14 days prior to Screening and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable). In addition, any participant that experiences pneumonia and/or moderate or severe COPD exacerbation during the
run-in period will be excluded.
9. Respiratory tract infection that has not resolved at least 7 days prior to Screening.
10. Participants with known COVID-19 positive contacts within the past 14 days should
be excluded for at least 14 days since the exposure and the subject remains symptom
free.
• Participants with symptoms suggestive of active COVID-19 infection e.g. fever,
cough (new or worsened), etc are also excluded
11. Abnormal Chest x-ray: Chest x-ray (posteroanterior and lateral) reveals evidence of
pneumonia or a clinically significant abnormality not believed to be due to the
presence of COPD, or another condition that would hinder the ability to detect an infiltrate on CXR (e.g. significant cardiomegaly, pleural effusion or scarring). All participants will have a chest x-ray at Screening Visit 1 (or historical radiograph or CT scan obtained within 3 months prior to screening).
12. Other diseases/abnormalities: Participants with historical or current evidence of
clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin,
sensory, endocrine (including uncontrolled diabetes or thyroid disease) or
haematological abnormalities that are uncontrolled. Significant is defined as any
disease that, in the opinion of the investigator, would put the safety of the participant
at risk through participation, or which would affect the efficacy or safety analysis if
the disease/condition exacerbated during the study.
13. Unstable liver disease as defined by the presence of ascites, encephalopathy,
coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent
jaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert’s
syndrome or asymptomatic gallstones).
Note: Chronic stable hepatitis B and C are acceptable if the participant otherwise
meets entry criteria.
14. Unstable or life threatening cardiac disease: participants with any of the following
at Screening (Visit 1) would be excluded:
• Myocardial infarction or unstable angina in the last 6 months
• Unstable or life-threatening cardiac arrhythmia requiring intervention in the last 3
months
• NYHA Class IV Heart failure
15. Abnormal and clinically significant 12-lead ECG finding at Visit 1
• The Investigator will determine the clinical significance of each abnormal ECG
finding in relation to the participant’s medical history and exclude participants
who would be at undue risk by participating in the trial.
• An abnormal and clinically significant finding that would preclude a participant
from entering the trial is defined as a 12-lead ECG tracing that is interpreted at,
but not limited to, any of the following:
i. Atrial Fibrillation (AF) with rapid ventricular rate >120 beats per
minute (BPM)
ii. Sustained and non-sustained Ventricular tachycardia (VT)
iii. Second degree heart block Mobitz type II and third degree heart block
(unless pacemaker or defibrillator had been inserted)
iv. QT interval corrected for heart rate of ≥500 msec in participants with
QRS <120 msec and QTcF ≥530 msec in participants with QRS ≥120 msec
16. Contraindications: A history of allergy or hypersensitivity to any corticosteroid,
anticholinergic/muscarinic receptor antagonist, β2-agonist, lactose/milk protein or
magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic
hypertrophy or bladder neck obstruction that, in the opinion of the Investigator,
contraindicates study participation.
17. Cancer: Participants with carcinoma that has not been in complete remission for at
least 5 years. Participants who have had carcinoma in situ of the cervix, squamous
cell carcinoma and basal cell carcinoma of the skin would not be excluded based on
the 5 year waiting period if the subject has been considered cured by treatment.
18. Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting
oxygen therapy >3L/min at screening (Oxygen use ≤3L/min flow at rest is not exclusionary.)
19. Pulmonary rehabilitation: participants must not start the acute phase of a pulmonary
rehabilitation program within the 4 weeks prior to Visit 1.
20. Medication prior to spirometry: Participants who are medically unable to withhold
their salbutamol for the 4-hour period required prior to spirometry testing at each study visit.
21. Drug/alcohol abuse: Participants with a known or suspected history of alcohol or drug abuse within the last 2 years.
22. Non-compliance: Participants at risk of non-compliance, or unable to comply with
the study procedures. Any infirmity, disability, or geographic location that would
limit compliance for scheduled visits.
23. Questionable validity of consent: Participants with a history of psychiatric disease,
intellectual deficiency, poor motivation or other conditions that will limit the validity
of informed consent to participate in the study.
24. Affiliation with investigator site: study investigators, sub-investigators, study
coordinators, employees of a participating investigator or study site, or immediate
family members of the aforementioned that is involved with this study.
25. Inability to read: In the opinion of the investigator, any participant who is unable to
read and/or would not be able to complete study related materials.
26. Medication prior to screening:Use of the following medications within the
following time intervals prior to Visit 1 or during the study:
-Antibiotic therapy: No use within 30 days prior to Screening
-Systemic, Oral, parenteral corticosteroids: No use within 30 days prior to Screening (Intra-articular injections are allowed)
-Any other investigational drug: No use within 30 days or 5 half lives whichever is longer prior to Screening
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate the safety profile of FF/UMEC/VI over 12 weeks in
patients from India
Endpoint: incidence of adverse events (AE), serious adverse events (SAE) and adverse events of special interest (AESIs)- Will be assessed at Visit 1, 2, 3, 5, Study Treatment discontinuation visit and at Safety Follow Up Visit 6.
Secondary Outcome
Outcome
TimePoints
To evaluate the effect of
FF/UMEC/VI on lung function
The secondary Estimands are defined by
the following:
• Endpoints:
- change from baseline in trough FEV1 on Day 85 (trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 24 hours after morning dosing on Day
84)
- change from baseline in trough FEV1 on Day 28 (trough FEV1 on
Day 28 is defined as the mean of the FEV1 values obtained prior to dosing on Day 28)
Target Sample Size
Total Sample Size="229" Sample Size from India="229" Final Enrollment numbers achieved (Total)= "229" Final Enrollment numbers achieved (India)="229"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The primary purpose of this study is to evaluate the safety and efficacy of a single inhaler triple therapy combination of FF/UMEC/VI (100mcg/62.5mcg/25mcg) administered once daily via the ELLIPTAâ„¢ inhaler, following 12 weeks of treatment.
Overall Design:
This is a phase IV, 12-week, single arm, multi-centre study evaluating single inhaler triple therapy (FF/UMEC/VI) once daily via the ELLIPTA (see Section 1.2 for study schematic). The target enrolment is 252 participants to enter the run-in period, at approximately 20 study centers in India. Participants will enter run-in on their existing COPD medication for 2 weeks. To ensure the participants enrolled are representative of the population that may be eligible for single inhaler triple therapy in India, prescription data from India will be used to cap the approximate number of patients enrolled on the
most widely prescribed COPD medications. At the end of the run-in period and start of the treatment period, participants will discontinue all existing COPD medications but may continue their study-supplied rescue salbutamol on an as-needed basis (rescue medication) throughout the study.
Clinic Visits will occur at Pre-Screening (Visit 0), Screening (Visit 1), Start of Treatment (Day 1, Visit 2), Day 28 (Visit 3), Day 84 (Visit 4) and Day 85 (Visit 5). A safety followup (Visit 6) telephone contact or clinic visit will be conducted 1 week after completing the 12-week treatment period. Participants will sign an informed consent form (ICF) at a Pre-Screen or Screening Visit and will be assigned a participant identifier.
Number of Participants:
Approximately 336 participants will be screened in order to recruit 252 participants to the
study run-in (assuming 25% screen failure) and 229 to the study treatment phase
(assuming 9% run-in failure) and achieve 220 evaluable participants at the end of the
study (assuming 4% withdrawal from study treatment).
Intervention Groups and Duration:
Participants who meet all the eligibility criteria and who have successfully completed all
protocol procedures at screening will enter the 2-week run-in period. Following the runin
period, eligible participants will receive the following study intervention for 12 weeks:
FF/UMEC/VI 100mcg/62.5mcg/25mcg via the ELLIPTA inhaler once daily in the
morning
On the morning of study clinic Visit 2 (start of treatment), Day 28 (Visit 3) and Day 84
(Visit 4), participants will refrain from taking their morning dose of study
intervention/COPD medication until instructed to do so by clinic personnel. Participants
will take their last dose of study treatment in the clinic on Day 84 and will return for their
final clinical assessments on Day 85 (Visit 5). A safety follow-up (Visit 6) will be
conducted either by phone call or clinic visit approximately one week later. Participants
may continue their study-supplied rescue salbutamol from the start of the run-in period
until the end of the treatment period.
A participant will be considered to have completed the study when they have completed
all phases of the study including screening, run-in, the treatment phase, and safety followup.
The total duration of participant participation will be approximately 15 weeks, consisting
of a 2-week run-in period, 12-week treatment period and a 1-week follow-up period.
Participants that permanently discontinue study intervention are not required to withdraw
from the study. If for any reason a participant must permanently discontinue study
treatment, every effort should be made by the investigator/staff to keep the participant in
the study. However, a participant may voluntarily withdraw from participation in this
study at any time. The investigator may also, at his or her discretion, withdraw a
participant from further study participation. Participants who are withdrawn from the