The purpose of the study is to evaluate the efficacy and safety of VX-548 in treating participants with PLSR.

Key Inclusion Criteria:

• Body weight greater than or equal to (>=)45 kilogram (kg)
• Body mass index (BMI) less than or equal to (<=) 40 kg/ meter square (m^2)
• Diagnosis of PLSR for greater than (>)3 months as per criteria pre-specified in the protocol
• Weekly average of daily NPRS score >=4 and <10 with limited variation in the 7-day Run-in Period

Key Exclusion Criteria:

• More than 3 missing daily NPRS scores during the 7-day Run-in Period
• Moderate or severe painful neuropathy other than PLSR as pre-specified in the protocol
• History of prior lumbar spine surgery (e.g., discectomies, laminectomies, foraminotomies, or fusion)

Other protocol defined Inclusion/Exclusion criteria may apply.

Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing