Inclusion Criteria:

Part A​
Adult Participants

• Participant (or their legally appointed and authorized representative) will sign and date an informed consent form (ICF), either in-person or remotely, as applicable by local law.
• Willing and able to comply with scheduled visits and other study procedures.
• Participants (male and female) between the ages of 18 and 65 years, inclusive.
• Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 based on the Modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2021)9 without the race adjustment. eGFR can be determined using the most recent serum creatinine value.
• A pre-existing diagnosis of ADPKD defined as follows:
  • Evidence of polycystic kidney disease in 1 or both biological parents AND meeting the Pei-Ravine classification criteria below:
    • The minimum number of cysts present for each age category are as follows:
      •  ≥3 cysts in between both kidneys for participants <40 years of age
      •  ≥2 cysts in each kidney for participants ≥40 and ≤59 years of age
      •  ≥4 cysts in each kidney for participants ≥60 years of age OR
  • In the absence of evidence of polycystic kidney disease in either biological parent, the presence of ≥10 cysts per kidney.

Part A
Pediatric Participants

• Participant and their legally appointed and authorized representative(s) will sign and date an ICF, and, when appropriate, an assent form, either in person or remotely, as applicable by local law.
• Willing and able to comply with scheduled visits and other study procedures.
• Participants (male and female) between the ages of 12 and 17 years, inclusive
• eGFR ≥30 mL/min/1.73 m2 based on the Chronic Kidney Disease in Children under 25 (CKiDU25) GFR estimating equation.eGFR can be determined using either the most recent historical serum creatinine value.
• A pre-existing diagnosis of ADPKD defined as follows:
  • Evidence of polycystic kidney disease in 1 or both biological parents OR compatible genetic diagnosis AND 
  • The presence of ≥1 renal cysts.

Part B (All Participants)

• Participant (or their legally appointed and authorized representative) will sign and date an ICF, and, when appropriate, an assent form either in person or remotely, as applicable by local law.
• Willing and able to comply with scheduled visits and other study procedures
• Completed Part A of the study.
• Received genotyping result confirming a non-truncating pathogenic, likely pathogenic, or variant of uncertain significance (VUS) within a sub-region of PKD1 that is eligible for Part B participation, as determined by Vertex or designee.
• TKV >500 mL based on the most recent historical value, if available. If TKV is not available, then kidney length >15 cm based on the most recent historical value.

Exclusion Criteria:

Parts A and B (All Participants)

• Participant, or close relative of the participant, is the investigator or a sub-investigator, research assistant, study coordinator, or other staff directly involved with the conduct of the study at that site.
• History of kidney disease other than ADPKD that in the opinion of the investigator would independently impact the natural history of ADPKD.
• History of solid organ or bone marrow transplantation or nephrectomy.
• Ongoing renal replacement therapy or planning to start renal replacement therapy ≤12 months from the Genotyping Visit in Part A.
• Documented historical genotype result demonstrating at least 1 truncating mutation in PKD1 (e.g., premature stop codon, frame shift variant, or splice junction variant).

Part B Only (All Participants)

In addition to exclusion criteria listed above participants in Part B must meet none of the following criteria:

• Presence of truncating mutation in PKD1 confirmed by the genotype result obtained in Part A.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 07/31/2024. Questions regarding updates should be directed to the study team contact.