Clinical trial NCT01744782: Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis
Official title: An Open-Label, Safety and Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naïve Patients With Cystinosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystinosis
Keywords: Nephropathic Cystinosis
Cysteamine
Delayed-release Cysteamine
CTNS Protein, Human
Orphan Disease
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-12-07
Enrollment: 17
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a long-term, open-label study of the safety, tolerability and effectiveness of RP103 in cystinosis patients who were naïve to any form of cysteamine treatment. Participants received RP103 treatment for at least 12 months. U.S. participants transitioned to the commercially approved drug PROCYSBI®. In Brazil, after at least 12 months of study participation and upon approval by the Brazilian regulatory authorities, participants were eligible to transition to a post-study drug supply program, and continue to receive the drug at no personal cost.

Detailed description: The purpose of this study was to gather information about the safety and effectiveness (how well it works to treat cystinosis) of a new drug called RP103.

In cystinosis, the body builds up cystine. When taken regularly, the active ingredient of an older, already approved drug called Cystagon® (cysteamine bitartrate) reduces cystine in the body. RP103 has the same active ingredient as Cystagon® and is designed to reduce cystine in a similar way that Cystagon® does. RP103 is also different from Cystagon®: Instead of the cysteamine bitartrate being absorbed from the stomach, RP103 is designed to be absorbed from the small intestine. This may make the effects of the drug last longer, so that it can be taken twice a day instead of four times a day like Cystagon®.

To decide if RP103 is effective, the study used two types of blood tests. One test is pharmacodynamics (PD), which measures the amount of white blood cell (WBC) cystine after taking study drug. WBC cystine is a laboratory test used to find out if cysteamine bitartrate is reducing cystine levels in the body. The second test is pharmacokinetics (PK), which measures the amount of cysteamine in the blood after taking the drug.

Study with completed results acquired from Horizon in 2024.

Eligibility criteria: Inclusion Criteria:

* Male or female with a documented diagnosis of cystinosis
* No clinically significant change in liver function tests, i.e. 1.5 times upper limit of normal (ULN) for alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and/or 1.5 times ULN for total bilirubin, within 6 months prior to Screening
* No clinically significant change in renal function, i.e. estimated glomerular filtration rate (GFR) within 6 months prior to Screening
* Must have an estimated GFR \> 20 mL/minute/1.73m² (using the equation from Schwartz 2009 J Am Soc Nephrol 20:629-647)
* Female participants who are sexually active and of childbearing potential, i.e. not surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy) or at least 2 years naturally postmenopausal must agree to use an acceptable form of contraception from Screening through completion of the study. Acceptable forms of contraception for this study include hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to Screening, barrier (spermicidal condom or diaphragm with spermicide), IUD, or a partner who has been vasectomized for at least 6 months. Childbearing potential was defined as a female who had reached menarche.
* Participant or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study
* Had not taken any form of cysteamine bitartrate in the past

Exclusion Criteria:

* Current history of the following conditions or any other health issues that make it, in the opinion of the Investigator, unsafe for study participation:
* Inflammatory bowel disease if currently active, or prior resection of the small intestine
* Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias, or poorly controlled hypertension) within 90 days prior to Screening
* Active bleeding disorder within 90 days prior to Screening
* History of malignant disease within 2 years prior to Screening
* Hemoglobin level of \< 10 g/dL at Screening or, in the opinion of the investigator, a hemoglobin level that would make it unsafe for study participation
* Known hypersensitivity to penicillamine
* Female subjects who were nursing, planning a pregnancy, or were known or suspected to be pregnant
* Participants who, in the opinion of the investigator, were not able or willing to comply with study requirements
* Had received a kidney transplant or was currently on dialysis
* Was 6 years of age or older at the time of the Screening visit

Primary outcomes:
measure: Mean White Blood Cell (WBC) Cystine Concentration at Each Visit
timeFrame: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Month 6, Month 9, Month 12, Month 15, Month 18, Study Exit
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Day 1 through study exit
measure: Maximum Observed Plasma Concentration (Cmax) of Cysteamine
timeFrame: 30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later
measure: Time of the Maximum Observed Plasma Concentration (Tmax) of Cysteamine
timeFrame: 30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of Cysteamine
timeFrame: 30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Sao Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo
state: SP
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21.