NCT03912233 is a Phase 2 clinical trial of VX-121 in Cystic Fibrosis, sponsored by Vertex Pharmaceuticals Incorporated.

Who is sponsoring NCT03912233?

NCT03912233 is sponsored by Vertex Pharmaceuticals Incorporated.

What drugs are being tested in NCT03912233?

Interventions in NCT03912233: VX-121, TEZ, VX-561, TEZ/IVA, IVA, Placebo.

What condition does NCT03912233 study?

NCT03912233 studies Cystic Fibrosis.

Is NCT03912233 still recruiting?

NCT03912233 is currently completed. Last updated 20 April 2023.

Are results published for NCT03912233?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2023-04-20 · How we verify

NCT03912233

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis

Completed Phase 2 Results posted Last updated 20 April 2023

What this trial tests

Phase 2 trial testing VX-121 in Cystic Fibrosis in 87 participants. Completed in 10 December 2019.

Timeline

30 April 2019

Primary endpoint
10 December 2019

10 December 2019

Quick facts

Lead sponsor	Vertex Pharmaceuticals Incorporated
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	quadruple
Primary purpose	treatment
Enrollment	87
Start date	30 April 2019
Primary completion	10 December 2019
Estimated completion	10 December 2019
Sites	26 locations across Netherlands, United Kingdom, Germany, Portugal, United States

Drugs / interventions tested

VX-121
TEZ — full drug profile →
VX-561 — full drug profile →
TEZ/IVA — full drug profile →
IVA — full drug profile →
Placebo

Conditions studied

Cystic Fibrosis — all drugs for Cystic Fibrosis →

Sponsor

Vertex Pharmaceuticals Incorporated — full company profile →

Who can join

18 and older, any sex, with Cystic Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)

Participants With AEs

Group	Value	95% CI
Part 1: Placebo	9
Part 1: VX-121/TEZ/VX-561 TC - Low Dose	8
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	16
Part 1: VX-121/TEZ/VX-561 TC - High Dose	20
Part 2: TEZ/IVA	8
Part 2: VX-121/TEZ/VX-561 TC - High Dose	16

Participants With SAEs

Group	Value	95% CI
Part 1: Placebo	2
Part 1: VX-121/TEZ/VX-561 TC - Low Dose	1
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	1
Part 1: VX-121/TEZ/VX-561 TC - High Dose	0
Part 2: TEZ/IVA	0
Part 2: VX-121/TEZ/VX-561 TC - High Dose	0

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Primary · From Baseline Through Day 29

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Group	Value	95% CI
Part 1: Placebo	1.9	-4.1 – 8.0
Part 1: VX-121/TEZ/VX-561 TC - Low Dose	4.6	-1.3 – 10.6
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	14.2	10.0 – 18.4
Part 1: VX-121/TEZ/VX-561 TC - High Dose	9.8	5.7 – 13.8
Part 2: TEZ/IVA	-0.1	-6.4 – 6.1
Part 2: VX-121/TEZ/VX-561 TC - High Dose	15.9	11.3 – 20.6

Absolute Change in Sweat Chloride (SwCl) Concentrations Secondary · From Baseline Through Day 29

Sweat samples were collected using an approved collection device.

Group	Value	95% CI
Part 1: Placebo	2.3	-7.0 – 11.6
Part 1: VX-121/TEZ/VX-561 TC - Low Dose	-42.8	-51.7 – -34.0
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	-45.8	-51.9 – -39.7
Part 1: VX-121/TEZ/VX-561 TC - High Dose	-49.5	-55.9 – -43.1
Part 2: TEZ/IVA	-2.6	-8.2 – 3.1
Part 2: VX-121/TEZ/VX-561 TC - High Dose	-45.5	-49.7 – -41.3

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Secondary · From Baseline at Day 29

The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Group	Value	95% CI
Part 1: Placebo	3.3	-10.1 – 16.6
Part 1: VX-121/TEZ/VX-561 TC - Low Dose	17.6	3.5 – 31.6
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	21.2	11.9 – 30.6
Part 1: VX-121/TEZ/VX-561 TC - High Dose	29.8	21.0 – 38.7
Part 2: TEZ/IVA	-5.0	-16.9 – 7.0
Part 2: VX-121/TEZ/VX-561 TC - High Dose	19.4	10.5 – 28.3

Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) Secondary · Pre-dose at Day 15 and Day 29

Day 15: VX-121 5 mg

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	317	± 119

Day 29: VX-121 5 mg

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	366	± 130

Day 15: VX-121 10 mg

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	520	± 214

Day 29: VX-121 10 mg

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	582	± 342

Day 15: VX-121 20 mg

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	974	± 500
Part 2: VX-121/TEZ/VX-561 TC - High Dose	1050	± 414

Day 29: VX-121 20 mg

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	1160	± 592
Part 2: VX-121/TEZ/VX-561 TC - High Dose	1030	± 371

Day 15: TEZ

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	1890	± 925
Part 2: VX-121/TEZ/VX-561 TC - High Dose	1870	± 675

Day 29: TEZ

Group	Value	95% CI
Part 1: VX-121/TEZ/VX-561 TC - Combined	1920	± 994
Part 2: VX-121/TEZ/VX-561 TC - High Dose	2070	± 1340

Adverse events — posted to ClinicalTrials.gov

Time frame: From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: Placebo

Serious: 2/10 (20%)

Deaths: 0/10

Part 1: VX-121/TEZ/VX-561 TC - Low Dose

Serious: 1/9 (11%)

Deaths: 0/9

Part 1: VX-121/TEZ/VX-561 TC - Medium Dose

Serious: 1/19 (5%)

Deaths: 0/19

Part 1: VX-121/TEZ/VX-561 TC - High Dose

Serious: 0/20 (0%)

Deaths: 0/20

Part 2: TEZ/IVA

Serious: 0/10 (0%)

Deaths: 0/10

Part 2: VX-121/TEZ/VX-561 TC - High Dose

Serious: 0/18 (0%)

Deaths: 0/18

Serious adverse events (3 terms)

Reaction	System	Part 1: Placebo	Part 1: VX-121/TEZ/VX-561 …	Part 1: VX-121/TEZ/VX-561 …	Part 1: VX-121/TEZ/VX-561 …	Part 2: TEZ/IVA	Part 2: VX-121/TEZ/VX-561 …
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	—	—	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Urticaria	Skin and subcutaneous tissue disorders	—	—	—	—	—	—

Other adverse events (122 terms — click to expand)

Reaction	System	Part 1: Placebo	Part 1: VX-121/TEZ/VX-561 …	Part 1: VX-121/TEZ/VX-561 …	Part 1: VX-121/TEZ/VX-561 …	Part 2: TEZ/IVA	Part 2: VX-121/TEZ/VX-561 …
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Sputum increased	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Palpitations	Cardiac disorders	—	—	—	—	—	—
Ear pain	Ear and labyrinth disorders	—	—	—	—	—	—
Swelling of eyelid	Eye disorders	—	—	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—
Frequent bowel movements	Gastrointestinal disorders	—	—	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Post-tussive vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Salivary hypersecretion	Gastrointestinal disorders	—	—	—	—	—	—

Most-reported serious reactions: Infective pulmonary exacerbation of cystic fibrosis, Breast cancer, Urticaria.

Data from ClinicalTrials.gov NCT03912233 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Targeting fibrosis, mechanisms and cilinical trials.
Zhao M, Wang L, Wang M, Zhou S, et al · · 2022 · cited 352× · PMID 35773269 · DOI 10.1038/s41392-022-01070-3
CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine.
Lopes-Pacheco M. · · 2019 · cited 349× · PMID 32153386 · DOI 10.3389/fphar.2019.01662
Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials.
Uluer AZ, MacGregor G, Azevedo P, Indihar V, et al · · 2023 · cited 51× · PMID 36842446 · DOI 10.1016/s2213-2600(22)00504-5
Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis.
Pinto MC, Silva IAL, Figueira MF, Amaral MD, et al · · 2021 · cited 37× · PMID 34326672 · DOI 10.2147/jep.s255377
Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
Southern KW, Murphy J, Sinha IP, Nevitt SJ. · · 2020 · cited 32× · PMID 33331662 · DOI 10.1002/14651858.cd010966.pub3
The Distribution and Role of the CFTR Protein in the Intracellular Compartments.
Lukasiak A, Zajac M. · · 2021 · cited 23× · PMID 34832033 · DOI 10.3390/membranes11110804
Treatment of Pulmonary Disease of Cystic Fibrosis: A Comprehensive Review.
Girón Moreno RM, García-Clemente M, Diab-Cáceres L, Martínez-Vergara A, et al · · 2021 · cited 20× · PMID 33922413 · DOI 10.3390/antibiotics10050486
Transcriptomic and Proteostasis Networks of CFTR and the Development of Small Molecule Modulators for the Treatment of Cystic Fibrosis Lung Disease.
Strub MD, McCray PB. · · 2020 · cited 13× · PMID 32414011 · DOI 10.3390/genes11050546

Verify or expand the search:

Other recruiting trials for Cystic Fibrosis

Currently open trials in the same condition.

NCT07437105 — Dose Escalation Study Evaluating the Safety and Pharmacokinetics of VX-272 in Healthy Participants · Phase 1 · recruiting
NCT07283770 — Dose Escalation Study Evaluating the Safety and Pharmacokinetics of VX-581 in Healthy Participants · Phase 1 · recruiting
NCT07274631 — A Cohort for Inflammatory Respiratory Diseases: From Phenotyping to Personalised Medicine · recruiting
NCT06810167 — Assessing Tenapanor as a Treatment of CF-related Constipation. · Phase 3 · recruiting
NCT06962852 — A Long-term Study to Monitor the Health Status of People With Cystic Fibrosis Who Took Part in a Previous Study With BI · Phase 1, PHASE2 · active not recruiting

Other Vertex Pharmaceuticals Incorporated trials

Trials by the same sponsor.

NCT05951205 — Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/ βC Ge · Phase 3 · withdrawn
NCT07501702 — A Phase 2 Study to Evaluate Povetacicept in Adults With Generalized Myasthenia Gravis · Phase 2 · not yet recruiting
NCT07437105 — Dose Escalation Study Evaluating the Safety and Pharmacokinetics of VX-272 in Healthy Participants · Phase 1 · recruiting
NCT07378865 — Evaluation of the Excretion of Suzetrigine Into Breast Milk in Healthy Lactating Female Participants · Phase 1 · recruiting
NCT07349394 — Effect of Vanzacaftor/Tezacaftor/Deutivacaftor (VNZ/TEZ/D-IVA) on the PK of Rosuvastatin in Healthy Participants · Phase 1 · completed

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03912233 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Vertex Pharmaceuticals Incorporated
Last refreshed: 20 April 2023

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03912233.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing