Patiromer for Treatment of Hyperkalaemia in Children Under 12 Years of Age

A 2-Part, Open-Label, Phase 2, Multiple Dose Study to Evaluate the Pharmacodynamic Effects, Safety, and Tolerability of Patiromer in Children Under 12 Years of Age With Hyperkalaemia (EMERALD2)

A study to evaluate the pharmacodynamic effects, safety, and tolerability of patiromer in children under 12 years of age with hyperkalaemia

Study Overview

• Status: Recruiting
• Conditions: Hyperkalemia
• Intervention / Treatment: Drug: Patiromer

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: EMERALD-2 Clinical Study Team; Phone Number: +41 58 851 80 00; Email: clinicaltrials@cslbehring.com

Study Locations

• Israel
  • Jerusalem, Israel, 9103102
    • Recruiting
    • Investigator Site 37602
  • Petah tikva, Israel, 4920235
    • Recruiting
    • Investigator Site 37601
• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Recruiting
      • Investigator Site 84006
    • Miami, Florida, United States, 33124
      • Not yet recruiting
      • Investigator Site 84003
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Recruiting
      • Investigator Site 84004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 5 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The following inclusion criteria must be met for each subject:

• Paediatric subjects (<12 years of age) with hyperkalaemia at screening.
• Subject's age should not reach 12 years during the 28 days of the pharmacodynamic (PD)/dose-ranging period.
• Subject is able to receive regular external feeding and medication, including via tubes, e.g., percutaneous endoscopic gastrostomy (PEG or entero-gastric feeding tube).
• At screening/baseline, the results from 2 separate and consecutive potassium assessments using the same measurement method (whole blood, plasma, or serum) need to be above the age-appropriate ULN.
• If taking any renin-angiotensin aldosterone system inhibitors (RAASi), beta blockers, fludrocortisone, or diuretic medications, must be on a stable dose for at least 14 days prior to screening.
• Parent(s) or legally authorised representative(s) or another appropriate person delegated by the legally authorised representatives must be available to help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day; accurately and reliably dispense investigational product as directed.
• Females of child bearing potential must be non-lactating, must have a negative pregnancy test at screening, and must have used an effective, acceptable form of contraception (e.g., abstinence) for at least 1 month before patiromer administration. Females of child bearing potential must agree to continue using contraception throughout the study and for 1 month after the last dose of patiromer.

Exclusion Criteria:

The following criteria exclude a subject from participating in this trial:

• Preterm birth infants with <37 weeks of gestation cannot be included in Cohort 3.
• Participants who due to their general condition, e.g., anaemia or low body weight, are not suitable to have blood volume withdrawn.
• Any of the following renal conditions: maintenance haemodialysis or peritoneal dialysis, renal artery stenosis, and acute kidney injury (defined by 2012 Kidney Disease Improving Global Outcomes) or a history of acute renal insufficiency in the past 3 months. Note: Chronic kidney disease (CKD) is not excluded.
• A history of or current diagnosis of a severe gastrointestinal (GI) diagnosis or surgery that could affect GI transit of the drug (delayed gastric emptying), such as a severe swallowing disorder, severe gastroesophageal reflux, uncorrected pyloric stenosis, intussusception, any other intestinal obstruction (e.g., Hirschsprung disease, chronic intestinal pseudo-obstruction, clinically significant postsurgical abdominal adhesions) or any gut-shortening surgical procedure prior to screening. Pre-gastric above-mentioned pathologies may be disregarded in case of existence of a PEG or entero-gastric feeding tube, as the PEG or entero-gastric feeding tube will serve for nutrition and investigational product administration.
• Active cancer, currently on cancer treatment, or history of cancer in the past 2 years (except for non-melanoma skin cancer).
• Recipient of any organ transplant requiring treatment with immunosuppressive therapy or scheduled for kidney transplant procedure during the first 28 days after Day 1.
• History of sudden infant death in a sibling (only for participants <2 years of age at screening).
• Use of the following medications if doses have not been stable for at least 14 days prior to screening or if doses are anticipated to change during the 4-week PD/ dose-ranging period: digoxin, bronchodilators, theophylline, heparins (including low molecular heparins), tacrolimus, mycophenolate mofetil, cyclosporine, trimethoprim, or cotrimoxazole.
• Use of any investigational product for an unapproved indication within 30 days prior to screening or within 5 half-lives, whichever is longer.
• Known hypersensitivity to patiromer or its components.

• If the child is being breastfed:

  1. There is suspicion of current alcohol or substance misuse/abuse in breastfeeding mother
  2. The breastfeeding mother is taking potassium supplements

Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patiromer; 4-week pharmacodynamic (PD)/dose-ranging period Cohort 1: 6 to <12 years of age Cohort 2: 2 to <6 years of age Cohort 3: 0 to <2 years of age); In Cohort 3, a minimum of 3 study participants will be assessed in the sub-group of 0 to <6 months and another 3 study participants in the sub-group 6 to <24 months of age.	Drug: Patiromer; Patiromer will be given once daily; In Cohort 3, depending on the dose and the study participant's age, the total daily dose might be split

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in potassium levels (mmol/L)	May be measured as serum, plasma, whole blood, potassium	From baseline to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of treatment-emergent adverse events (TEAEs)		Part 1: Day 1 up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to follow-up visit (Up to 54 weeks)
Occurrence of serious adverse events (SAEs)		Part 1: Day 1 up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to follow-up visit (Up to 54 weeks)
Change from baseline in resting heart rate (beats per minute)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in systolic blood pressure (mmHg)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in diastolic blood pressure (mmHg)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in body temperature (Celsius)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Number of patients with ECG abnormalities		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Calcium (mg/dL)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Phosphate (mg/dL)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Magnesium (mg/dL)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Potassium (mEq/L)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Sodium (mEq/L)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Creatinine (mg/dL)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Serum bicarbonate (mEq/L)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in chemistry laboratory evaluation: Blood urea nitrogen (mEq/L)		From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
Change from baseline in haematology laboratory evaluation: White blood cells (10^9/L)		From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
Change from baseline in haematology laboratory evaluation: Red blood cells count (10^12/L)		From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
Change from baseline in haematology laboratory evaluation: Haemoglobin (10^12/L)		From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
Change from baseline in haematology laboratory evaluation: Haematocrit (%)		From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
Change from baseline in haematology laboratory evaluation: Platelet count (10^9/L)		From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
Change from baseline in haematology laboratory evaluation: Blood fluoride (ng/mL)		From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
Occurrence of blood potassium below the lower limit of normal (LLN) (mmol/L)		Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks)
Occurrence of blood potassium above the upper limit of normal (ULN) (mmol/L)		Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks)
Occurrence of blood magnesium at levels specified in protocol (mmol/L)		Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks)
Occurrence of abnormal clinical laboratory value findings	Occurrence of clinical laboratory value findings that are outside of normal range of the respective age for: serum calcium, phosphate, fluoride, creatinine, bicarbonate, and blood urea nitrogen levels	Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks)
Change in potassium levels (mmol/L)	May be measured as serum, plasma, whole blood, potassium	From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks

Collaborators and Investigators

• Sponsor: Vifor Pharma, Inc.
• Investigators: Study Director: Julian Platon, MD, PhD, Vifor Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia
• Other Study ID Numbers: RLY5016-208p; 2023-505252-21-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL Vifor acknowledges the importance of data transparency and commits to sharing, upon request from qualified scientific researchers, patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials for medicines and indications approved in the United States (US) and the European Union (EU).
• IPD Sharing Time Frame: Data from Vifor Pharma sponsored non-interventional and interventional clinical trials (phase 1-4) for medicines and indications approved in the US and the EU, will be shared if the evaluation of the request is positive and two years have elapsed since study completion or termination of the program.
• IPD Sharing Access Criteria: Data is shared upon request from qualified scientific researchers under the prerequisite that the trial subjects' rights are kept fully protected, in particular with regards to Good Clinical Practice and Data Privacy, that the proposed analyses aim to yield an appropriate and valid scientific output and are not in conflict with the publication plan for the study. Requests should be submitted including a description of the data requested, a rationale for the proposed research, a Statistical Analysis Plan, a Publication Plan, qualifications and experience of the research team, disclosure of any conflicts of interests and competitive use of data, and source of research funding. If after evaluation the request is approved, the process of sharing the requested data will be initiated. As a prerequisite, a signed personal data processing and transfer agreement between Vifor Pharma and the data requestor is required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No