Clinical trial NCT01197378: Long-Term Safety Follow-up Study of Cysteamine Bitartrate Delayed-release Capsules (RP103)
Official title: A Long-Term, Open-Label, Safety and Efficacy Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Patients With Cystinosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystinosis
Keywords: cystinosis
cysteamine
inheritable disease
orphan disease
CTNS protein, human
metabolic disease
nephropathic cystinosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-09-09
Enrollment: 60
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Cystinosis is an inherited disease that if untreated, results in kidney failure as early as the first decade of life. The current marketed therapy is Cystagon® (cysteamine bitartrate immediate release) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. Cysteamine bitartrate delayed-release capsules (RP103) is a formulation of cysteamine bitartrate that is being studied to see if it can be given less frequently, once every 12 hours, and have similar results to four times a day Cystagon®.

Detailed description: This is a long-term, open-label, study to determine the safety and tolerability of twice a day treatment with cysteamine bitartrate delayed-release capsules (RP103). It will involve 6-9 monthly clinic visits followed by quarterly clinic visits for the duration of the study and home use of cysteamine bitartrate delayed-release capsules.

Initially, enrollment was open to those patients who had completed the previous Phase 3 Study (RP103-03, NCT01000961). Subsequently enrollment in Study RP103-04 was opened to additional participants, including children aged 1 to 6 years and renal transplant recipients, who had previously been on a stable dose of Cystagon® for at least 21 days.

Study with completed results acquired from Horizon in 2024.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects must have completed the last visit of Study RP103-03 and be willing to continue with RP103 treatment.

OR for patients who did not complete the RP103-03 study:

* Male and female subjects must have cystinosis.
* Subjects must be on a stable dose of Cystagon® at least 21 days prior to Screening.
* Within the last 6 months, no clinically significant change from normal in liver function tests (i.e., alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], total bilirubin) and renal function (i.e., estimated glomerular filtration rate \[eGFR\]) at Screening as determined by the Investigator.
* Subjects with an eGFR corrected for body surface area \> 30 mL/min/1.73m².
* Sexually active female subjects of childbearing potential (i.e., not surgically sterile \[tubal ligation, hysterectomy, or bilateral oophorectomy\] or at least 2 years naturally postmenopausal) must agree to utilize the same acceptable form of contraception from Screening through completion of the study.
* Subjects must be willing and able to comply with the study restrictions and requirements.
* Subjects or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.

Exclusion Criteria:

* Patients enrolled in the previous Study RP103-03 who did not complete their last scheduled Study visit or who do not wish to continue on treatment with RP103.

AND for patients who did not complete the RP103-03 study:

* Subjects less than 1 year old
* Subjects with a known history, currently of the following conditions or other health issues that make it, in the opinion of the investigator, unsafe for them to participate: inflammatory bowel disease (if currently active) or have had prior resection of small intestine; Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias or poorly controlled hypertension) 90 days prior to Screening; Active bleeding disorder 90 days prior to Screening; Malignant disease within the last 2 years.
* Patients with a hemoglobin level \< 10 g/dL at Screening or a level that, in the opinion of the investigator, makes it unsafe for the subject to participate.
* Subjects with known hypersensitivity to cysteamine or penicillamine.
* Female subjects who are nursing, planning a pregnancy, known or suspected to be pregnant, or have a positive serum pregnancy screen.
* Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days.
Secondary outcomes:
measure: Trough Plasma Cysteamine Concentration
timeFrame: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
measure: White Blood Cell Cystine Concentration
timeFrame: Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: California Pacific Medical Center (CPMC) Research Institute
state: California
city: Stanford
country: United States
facility: Stanford University Medical School
state: California
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Houston
country: United States
facility: Texas Children's Hospital/Baylor University
state: Texas
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Montpellier
country: France
facility: Hôpital Arnaud Villeneuve - CHU Montpellier
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Robert Debre Hospital
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Center
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Dohil R, Fidler M, Barshop BA, Gangoiti J, Deutsch R, Martin M, Schneider JA. Understanding intestinal cysteamine bitartrate absorption. J Pediatr. 2006 Jun;148(6):764-9. doi: 10.1016/j.jpeds.2006.01.050.
citation: Fidler MC, Barshop BA, Gangoiti JA, Deutsch R, Martin M, Schneider JA, Dohil R. Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. Br J Clin Pharmacol. 2007 Jan;63(1):36-40. doi: 10.1111/j.1365-2125.2006.02734.x.
citation: Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA, Blom HJ. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006 Jan;21(1):110-3. doi: 10.1007/s00467-005-2052-0. Epub 2005 Oct 27.
citation: Langman CB, Greenbaum LA, Grimm P, Sarwal M, Niaudet P, Deschenes G, Cornelissen EA, Morin D, Cochat P, Elenberg E, Hanna C, Gaillard S, Bagger MJ, Rioux P. Quality of life is improved and kidney function preserved in patients with nephropathic cystinosis treated for 2 years with delayed-release cysteamine bitartrate. J Pediatr. 2014 Sep;165(3):528-33.e1. doi: 10.1016/j.jpeds.2014.05.013. Epub 2014 Jun 16.