Phase 2a Study of VX-407 in Subjects with ADPKD Who Have a Subset of PKD1 Gene Variants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vertex Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Genetic Phenomena [G05]

Trial duration

2 Dec 2025 → ongoing

Decision date (initial)

2025-12-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

Treatment of ADPKD with VX-407

Secondary objectives 2

1. To evaluate the safety, and tolerability of VX-407.
2. To evaluate the PK of VX-407

Conditions and MedDRA coding

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subjects between the ages of 18 and 65 years, inclusive at the time of signing the Screening Period ICF.
2. A body mass index (BMI) of 18 to 45 kg/m2, inclusive (Note: this may be adjusted based on the available data from Study 001).
3. Subjects with a pre-existing diagnosis of ADPKD defined as: • Evidence of polycystic kidney disease in 1 or both biological parents AND meeting the Pei-Ravine classification criteria14 as defined below The minimum number of cysts present for each age category as follows:  ≥3 cysts in between both kidneys for participants <40 years of age  ≥2 cysts in each kidney for participants ≥40 years of age and ≤59 years of age  ≥4 cysts in each kidney for participants ≥60 years of age OR • In the absence of a family history of ADPKD: The presence of ≥10 cysts per kidney
4. Subjects with ADPKD with Mayo imaging classification (MIC) status of 1B (with htTKV ≥250 mL/m), 1C, 1D, or 1E15 confirmed by abdominal MRI obtained during screening. A maximum of 5 subjects with MIC status of 1B who have htTKV ≥250 mL/m may be enrolled.
5. Subject has a non-truncating variant that is pathogenic, likely pathogenic, or variant of uncertain significance (VUS) within a sub-region of PKD1 and no additional truncating PKD1 variants confirmed by results obtained with a Vertex-designated investigational clinical study assay.
6. eGFR ≥25 ml/min/1.73 m2 based on the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2021) creatinine equation without the race adjustment.

Exclusion criteria 2

1. History of any illness or any clinical condition that, in the opinion of the investigator or the subject’s general practitioner, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to: • Kidney disease other than ADPKD that in the opinion of the investigator would independently impact the natural history of ADPKD • Solid organ or bone marrow transplantation, or nephrectomy • Any condition possibly affecting drug absorption (e.g., gastrectomy, gastrointestinal tract surgery except appendectomy and cholecystectomy) • Clinically significant liver dysfunction • Cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no recurrence for the last 5 years) • Stroke or myocardial infarction within 6 months before Day 1 • Hospitalization for heart failure exacerbation within the past year • Risk factors for Torsades de Pointes (e.g., familial long QT syndrome, chronic hypokalemia, heart failure) or concomitant medications that prolong QT/QTc interval or history of any cardiac disorders that, in the opinion of the investigator, might put the subject at risk or may confound the results of the study
2. Subjects who, in the opinion of the investigator, have evidence of atypical ADPKD presentation (MIC 2).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects with percent change from baseline in htTKV ≤0 on MRI over time

Secondary endpoints 3

1. Percent change from baseline in htTKV on MRI over time
2. Safety and tolerability of VX¬407 based on adverse events (AEs), clinical laboratory values (i.e., hematology, serum chemistry, coagulation), standard 12-lead ECGs, and vital signs
3. Plasma PK parameters of VX 407

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vertex Pharmaceuticals Inc.

Sponsor organisation

Vertex Pharmaceuticals Inc.

Address

50 Northern Avenue

City

Boston

Postcode

02210-1862

Country

United States

Scientific contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Public contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Locations

6 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 123 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications