Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 Combination Therapy in Adult Participants With Cystic Fibrosis

• Sponsor: AbbVie (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04853368
• Collaborator: (none)
• Enrollment: 90
• Locations: 27
• Arms: 4
• Anticipated Duration (Months): 13
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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 are homozygous or heterozygous for the F508del mutation in each arm.

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.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis (CF)	Drug: Galicaftor; Drug: Placebo; Drug: Navocaftor; Drug: ABBV-119	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Sep 13, 2021
• Anticipated Primary Completion Date: Sep 9, 2022
• Anticipated Study Completion Date: Oct 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: F508del Homozygous Cystic Fibrosis (CF) Participants F508del homozygous cystic fibrosis (CF) participants receive galicaftor/navocaftor dual combination (28 days) followed by galicaftor/navocaftor/ABBV-119 triple combination therapy (28 days).	Drug: Galicaftor; Oral capsules; Drug: Navocaftor; Oral capsules; Drug: ABBV-119; Oral capsules
Experimental: F508del Heterozygous CF Participants (Active Drug Group) F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days).	Drug: Galicaftor; Oral capsules; Drug: Navocaftor; Oral capsules; Drug: ABBV-119; Oral capsules
Placebo Comparator: F508del Heterozygous CF Participants (Placebo Group) F508del heterozygous CF participants receive placebo (28 days).	Drug: Placebo; Oral capsules
Experimental: F508del Homozygous or Heterozygous CF Participants F508del homozygous or heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 triple combination therapy for 28 days	Drug: Galicaftor; Oral capsules; Drug: Navocaftor; Oral capsules; Drug: ABBV-119; Oral capsules

Outcome Measures

Primary Outcome Measures

1. Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [Up to 29 days]

   Percent predicted forced expiratory volume in 1 second (ppFEV1).

Secondary Outcome Measures

1. Absolute Change From Baseline in Sweat Chloride (SwCl) [Up to 29 days]

   Sweat chloride (SwCl) concentration is a biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function.

2. Absolute Change From Baseline in Forced Vital Capacity [FVC] [Up to 29 days]

   Forced vital capacity (FVC).

3. Absolute Change From Baseline in Forced Expiratory Flow at Mid-Lung Capacity [FEF25-75] [Up to 29 days]

   Forced expiratory flow between 25% and 75% of exhaled volume (FEF25-75).

4. Relative Changes From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [Up to 29 days]

   Percent predicted forced expiratory volume in 1 second (ppFEV1).

5. Relative Changes From Baseline in Forced Vital Capacity [FVC] [Up to 29 days]

   Forced vital capacity (FVC).

6. Relative Changes From Baseline in Forced Expiratory Flow Between 25% and 75% of Exhaled Volume (FEF25-75) [Up to 29 days]

   Forced expiratory flow between 25% and 75% of exhaled volume (FEF25-75).

7. Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline [Up to 29 days]

   The CFQ-R is designed for use in participants with a diagnosis of cystic fibrosis and is designed to measure impact on overall health, daily life, perceived well-being, and symptoms. Participants will complete the CFQ-R electronically via a tablet device.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed clinical diagnosis of cystic fibrosis (CF).

• Arm 1 participants with genotype homozygous for the F508del CF transmembrane conductance regulator (CFTR) mutation and not receiving elexacaftor/tezacaftor/ivacaftor (ETI) treatment .

• Arm 2 and 3 participants with genotype heterozygous for the F508del CFTR mutation and a minimal function and not receiving ETI treatment.

• Arm 4 participants with genotype either homozygous or heterozygous for the F508del mutation. Participants must be receiving stable (ETI) treatment.

• Percent predicted forced expiratory volume in 1 second (ppFEV1) >= 40% and <=90% of predicted normal for age, gender and height at screening.

• For arms 1,2 and 3: sweat chloride (SwCl) >= 60 mmol/L at screening. For participants who participated in Study M19-530, it is acceptable to use a SwCl value that the central lab provided in Study M19-530 to establish eligibility.

• Weight >= 35 kg at screening and Day -28 for arm 1 or day 1 for arms 2 to 4.

Exclusion Criteria:

• Clinically significant laboratory values at screening that would pose undue risk for the participant or interfere with safety assessments (per the investigator).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Prince Alfred Hospital /ID# 228781	Camperdown	New South Wales	Australia	2050
2	Westmead Hospital /ID# 227281	Westmead	New South Wales	Australia	2145
3	Mater Misericordiae Limited /ID# 227279	South Brisbane	Queensland	Australia	4101
4	Royal Adelaide Hospital /ID# 228486	Adelaide	South Australia	Australia	5000
5	Royal Children's Hospital /ID# 227280	Parkville	Victoria	Australia	3052
6	Institute for Respiratory Health /ID# 227624	Nedlands	Western Australia	Australia	6009
7	Uza /Id# 228533	Edegem	Antwerpen	Belgium	2650
8	UZ Brussel /ID# 226607	Jette	Bruxelles-Capitale	Belgium	1090
9	UZ Gent /ID# 226605	Gent	Oost-Vlaanderen	Belgium	9000
10	Universitair Ziekenhuis Leuven /ID# 226608	Leuven	Vlaams-Brabant	Belgium	3000
11	Universitaetsklinik Heidelberg /ID# 238499	Heidelberg	Baden-Wuerttemberg	Germany	69120
12	Pneumologisches Studienzentrum München-West /ID# 240765	Munich	Bayern	Germany	81241
13	Klinikum Westbrandenburg /ID# 240713	Potsdam	Brandenburg	Germany	14467
14	Universitaetsklinikum Frankfurt /ID# 238497	Frankfurt am Main	Hessen	Germany	60590
15	Universitaetsmedizin Essen - Ruhrlandklinik /ID# 238544	Essen	Nordrhein-Westfalen	Germany	45239
16	Universitaetsklinikum Koeln /ID# 238542	Köln	Nordrhein-Westfalen	Germany	50937
17	Universitaetsklinikum Jena /ID# 238535	Jena	Thueringen	Germany	07747
18	Medizinische Hochschule Hannover /ID# 238498	Hannover		Germany	30625
19	Orszagos Koranyi Pulmonologiai Intezet /ID# 228810	Budapest		Hungary	1121
20	Erasmus Medisch Centrum /ID# 234254	Rotterdam	Zuid-Holland	Netherlands	3015 GD
21	Academisch Medisch Centrum /ID# 234253	Amsterdam		Netherlands	1105 AZ
22	HagaZiekenhuis /ID# 234138	Den Haag		Netherlands	2545 AA
23	Greenlane Clinical Centre /ID# 227282	Epsom	Auckland	New Zealand	1051
24	Christchurch Hospital /ID# 227335	Christchurch	Canterbury	New Zealand	8011
25	Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 228044	Banska Bystrica		Slovakia	975 17
26	Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228041	Bratislava		Slovakia	821 01
27	Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228042	Bratislava		Slovakia	821 06

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: ABBVIE INC., AbbVie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT04853368
• Other Study ID Numbers: M19-771; 2020-005805-25
• First Posted: Apr 21, 2021
• Last Update Posted: May 16, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by AbbVie: Cystic Fibrosis (CF); Galicaftor; Navocaftor; ABBV-119
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

No Results Posted as of May 16, 2022