A study to evaluate the safety, tolerability, and efficacy of galicaftor/navocaftor/ABBV-119 combination therapy in subjects with cystic fibrosis
| ISRCTN | ISRCTN48897533 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN48897533 |
| ClinicalTrials.gov (NCT) | NCT04853368 |
| Clinical Trials Information System (CTIS) | 2020-005805-25 |
| Integrated Research Application System (IRAS) | 1004477 |
| Protocol serial number | M19-771, IRAS 1004477, CPMS 51119 |
| Sponsor | AbbVie (United Kingdom) |
| Funder | AbbVie |
- Submission date
- 28/01/2022
- Registration date
- 07/03/2022
- Last edited
- 05/01/2024
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Cystic Fibrosis (CF) is a rare, life-threatening, genetic disease that affects the lungs and digestive system, significantly impairing the quality of life, with those affected having a median age of death at 40. The main objective of this study is to assess how safe and effective is the combination therapy of galicaftor/navocaftor/ABBV-119 in adult participants with CF
Who can participate?
Patients with CF, and the F508del CFTR mutation (the most common CF gene mutation)
What does the study involve?
Galicaftor/navocaftor/ABBV-119 combination therapy is being developed as an investigational drug for the treatment of CF. Study doctors place participants in 1 of the 4 groups, called treatment arms. Each group receives a different treatment. Around 90 adult participants with a diagnosis of CF will be enrolled in the study around approximately 35 sites worldwide.
Participants in arm 1 will receive oral capsules of galicaftor/navocaftor dual combination for 28 days followed by galicaftor/navocaftor/ABBV-119 triple combination for 28 days. Participants in arms 2 and 3 will receive the galicaftor/navocaftor/ABBV-119 triple combination or placebo for 28 days. Participants in arm 4 will receive galicaftor/navocaftor/ABBV-119 triple combination therapy for 28 days. For all study arms, galicaftor, navocaftor, will be given once daily and ABBV-119 twice a day.
What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
ABBV-119 A small number of healthy volunteers who received ABBV-119 for up to 14 days had elevated blood levels of liver enzymes (ALT and AST), a possible sign of injury to the liver. The volunteers did not have any complaints along with these abnormal blood tests. The tests returned to normal or near normal levels within the next 2 weeks. There could be a risk of side effects related to sunlight exposure or ultraviolet (UV) light exposure. It is not known whether exposure to sunlight might lead to skin irritation or cause one to break out in a rash or sunburn. If possible, patients should avoid direct exposure to the sun for long periods of time while participating in this clinical study. Protective clothing and sunglasses as well as sunscreen (SPF 30 or higher) should be used if exposed to sunlight. In addition, patients should not expose themselves to sun lamps, tanning booths, or tanning beds.
Most common side effects of the combination of galicaftor and navocaftor: Headache/Fatigue/Back pain/Constipation/Dry lips/Decreased urination/Nausea/Rash
Risks related to Study Procedures:
Blood Testing: may cause pain, bleeding, and/or bruising
Sweat collection: may cause tingling of the skin. The sticky pads may result in “irritation” of the skin. There is a remote possibility of a burn due to the test.
Lung Function Testing: may feel the need to cough, or feel a bit short of breath and lightheaded
5-day washout may lead to withdrawal symptoms
Where is the study run from?
St James's University Hospital (UK)
When is the study starting and how long is it expected to run for?
January 2022 to December 2022
Who is funding the study?
AbbVie Ltd (UK)
Who is the main contact?
Dr Daniel Peckham, daniel.peckham@nhs.net
Contact information
Principal investigator
St James's University Hospital
Beckett St
Leeds
LS9 7TF
United Kingdom
| Phone | +44 113 206 7170 |
|---|---|
| Daniel.Peckham@nhs.net |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional double blind randomized parallel group placebo controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | A phase 2 study of galicaftor/navocaftor/ABBV-119 combination therapy in subjects with cystic fibrosis who are homozygous or heterozygous for the F508del mutation |
| Study objectives | The primary objective is to evaluate the safety, tolerability, and efficacy for galicaftor/navocaftor/ABBV-119 combination therapy in adult subjects with CF who are homozygous or heterozygous for the F508del mutation. |
| Ethics approval(s) | Approval pending, HRA Fast Track REC, ref: 22/FT/0001 |
| Health condition(s) or problem(s) studied | Cystic Fibrosis |
| Intervention | Study doctors place participants in 1 of the 4 groups, called treatment arms. Each group receives a different treatment. Around 90 adult participants with a diagnosis of CF will be enrolled in the study at approximately 35 sites worldwide. Participants in arm 1 will receive oral capsules of galicaftor/navocaftor dual combination for 28 days followed by galicaftor/navocaftor/ABBV-119 triple combination for 28 days. Participants in arms 2 and 3 will receive the galicaftor/navocaftor/ABBV-119 triple combination or placebo for 28 days. Participants in arm 4 will receive galicaftor/navocaftor/ABBV-119 triple combination therapy for 28 days. For all study arms, galicaftor, navocaftor, will be given once daily and ABBV-119 twice a day. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | galicaftor, navocaftor, ABBV-119 |
| Primary outcome measure(s) |
The primary endpoint is the absolute change from Baseline through Day 29 in percent predicted forced expiratory volume in 1 second (ppFEV1) measured using spirometry |
| Key secondary outcome measure(s) |
Measured using spirometry unless noted otherwise: |
| Completion date | 16/12/2022 |
| Reason abandoned (if study stopped) | Objectives no longer viable |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 90 |
| Key inclusion criteria | 1. Confirmed clinical diagnosis of CF, and genotype homozygous for the F508del CFTR mutation for Cohort 1 and Cohort 3, heterozygous for F508del CFTR mutation and a minimal function mutation for Cohort 2 and Cohort 3. 2. ppFEV1 ≥40% and ≤90% of predicted normal for age, gender, and height (Global Lung Function Initiative [GLI] equations) at Screening. 3. No clinically significant laboratory values at Screening that would pose undue risk for the subject or interfere with safety assessments (per the investigator). 4. Absence of clinically significant abnormality detected on ECG regarding rate, rhythm, or conduction (e.g., QT interval corrected for heart rate using Fridericia's formula [QTcF] should be < 450 msec for males and <460 msec for females). 5. Stable pulmonary status, i.e., no respiratory infections or exacerbations requiring a change in therapy (including antimicrobials) or causing an acute decline in ppFEV1 of >10% from usual ppFEV1 level within 4 weeks. 6. SwCl at screening visit must be ≥60 mmol/L for Cohort 1 and Cohort 2, and this criterion does not apply to Cohort 3. 7. No history of diseases aggravated or triggered by ultraviolet radiation and no history of abnormal reaction photosensitivity or photoallergy to sunlight, or artificial source of intense light, especially ultraviolet light. |
| Key exclusion criteria | 1. Cirrhosis with or without portal hypertension (e.g., splenomegaly, esophageal varices) or history of clinically significant liver disease 2. History of malignancy within past 5 years (except for excised basal cell carcinoma of the skin with no recurrence, or treated carcinoma in situ of the cervix with no recurrence) 3. Recent (within the past 6 months) history of drug or alcohol abuse that might preclude adherence to the protocol, in the opinion of the investigator 4. Smoking or vaping tobacco or cannabis products within 6 months before Screening 5. History of solid organ or hematopoietic transplantation 6. History of known sensitivity to any component of the study drug 7. Need for supplemental oxygen while awake, or >2 L/minute while sleeping. 8. Evidence of active SARS-CoV-2 infection. If a subject has signs/symptoms suggestive of SARS CoV-2 infection, they should undergo molecular (e.g., polymerase chain reaction [PCR]) testing to rule out SARS-CoV-2 infection. |
| Date of first enrolment | 28/07/2021 |
| Date of final enrolment | 16/12/2022 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Belgium
- Canada
- France
- Hungary
- Netherlands
- Puerto Rico
- Serbia
- Slovakia
- Spain
Study participating centres
Papworth Road
Cambridge
CB2 0AY
United Kingdom
Glasgow
G51 4TF
United Kingdom
Penlan Road
Cardiff
CF64 2XX
United Kingdom
London
SE5 9RS
United Kingdom
London
SW3 6NP
United Kingdom
Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom
Southampton
SO16 6YD
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available. |
Editorial Notes
05/01/2024: The results from Cohorts 1 and 2 of trial M19-771 showed that the compound combination of triple therapy was not effective, and the HRA would not approve a protocol amendment to change one of the compounds for cohort 3 as the study wasn’t designed as a complex protocol. Therefore, the study was withdrawn during (cohort 3) set up and there was no recruitment.
29/04/2022: Contact details.
01/04/2022: added CPMS number to Protocol /serial number field.
05/03/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 05/03/2022
28/01/2022: Trial's existence confirmed by NHS HRA.
