Key Inclusion Criteria:  Adults ≥ 18 years old; Has end-stage renal disease (ESRD) and is currently receiving in-center hemodialysis; Has moderate-to-severe pruritus attributed to ESRD which is significantly impacting the patient's quality of life; Has no comparable or satisfactory alternative therapy for the treatment of moderate-to-severe pruritus, as determined by the sponsor-investigator.  Key Exclusion Criteria:  Has severe hepatic impairment (Child-Pugh class C), as the influence of severe hepatic impairment on the pharmacokinetics of difelikefalin has not been evaluated; Is pregnant or nursing; Has been exposed to any other investigational medication in the past 60 days; Present any other reason which may lead to an unfavorable risk-benefit ratio for treatment with difelikefalin, as determined by the sponsor-investigator; Has a known or suspected allergy to difelikefalin or any component of the investigational product.