Clinical trial NCT05766839: Patiromer for Treatment of Hyperkalaemia in Children Under 12 Years of Age
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hyperkalemia
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
First posted: 2023-03-13
Enrollment: 36
Sex: ALL
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in potassium levels (mmol/L)
timeFrame: From baseline to Day 28
Secondary outcomes:
measure: Change in potassium levels (mmol/L)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Occurrence of treatment-emergent adverse events (TEAEs)
timeFrame: 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)
measure: Occurrence of serious adverse events (SAEs)
timeFrame: 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)
measure: Change from baseline in resting heart rate (beats per minute)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in systolic blood pressure (mmHg)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in diastolic blood pressure (mmHg)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in body temperature (Celsius)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Number of patients with ECG abnormalities
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Calcium (mg/dL)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Phosphate (mg/dL)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Magnesium (mg/dL)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Potassium (mEq/L)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Sodium (mEq/L)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Creatinine (mg/dL)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Serum bicarbonate (mEq/L)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in chemistry laboratory evaluation: Blood urea nitrogen (mEq/L)
timeFrame: From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks
measure: Change from baseline in haematology laboratory evaluation: White blood cells (10^9/L)
timeFrame: From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
measure: Change from baseline in haematology laboratory evaluation: Red blood cells count (10^12/L)
timeFrame: From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
measure: Change from baseline in haematology laboratory evaluation: Haemoglobin (10^12/L)
timeFrame: From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
measure: Change from baseline in haematology laboratory evaluation: Haematocrit (%)
timeFrame: From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
measure: Change from baseline in haematology laboratory evaluation: Platelet count (10^9/L)
timeFrame: From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
measure: Change from baseline in haematology laboratory evaluation: Blood fluoride (ng/mL)
timeFrame: From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52)
measure: Occurrence of blood potassium below the lower limit of normal (LLN) (mmol/L)
timeFrame: 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)
measure: Occurrence of blood potassium above the upper limit of normal (ULN) (mmol/L)
timeFrame: 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)
measure: Occurrence of blood magnesium at levels specified in protocol (mmol/L)
timeFrame: 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)
measure: Occurrence of abnormal clinical laboratory value findings
timeFrame: 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)
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: UF Health Pediatric Multispecialty Center
state: Florida
city: Miami
country: United States
facility: Miller School of Medicine, University of Miami
state: Florida
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Durham
country: United States
facility: Duke University Hospital & Medical Center
state: North Carolina
city: Montpellier
country: France
facility: CHRU Montpellier - Arnaud de Villeneuve
city: Paris
country: France
facility: Assistance Publique-Hopitaux de Paris - Hopital Universitaire Robert-Debre
city: Toulouse
country: France
facility: Hôpital des Enfants - Toulouse
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikvah
country: Israel
facility: Schneider Children's Medical Center of Israel
Study officials:
affiliation: Vifor Pharma, Inc.
name: Julian Platon, MD, PhD
role: STUDY_DIRECTOR
References: