Open-Label, Safety and Superior Effectiveness Study of Cysteamine Bitartrate Delayed-Release Capsules (RP103) in Cystinosis

Amgen41 enrolled

Overview

The purpose of this study is to gather information about the effectiveness (how well it works to treat cystinosis) and safety of a new form of cysteamine bitartrate called RP103, compared to the already-approved drug cystinosis patients are taking called Cystagon®. In cystinosis, the body builds up cystine. When taken regularly, the active ingredient of 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. To decide if RP103 is better than Cystagon®, the study will look at 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. RP103 is 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®. Some cystinosis patients have bad breath (halitosis) when they take Cystagon®. Study participants who experience bad breath with Cystagon® will be asked if they would like to participate in an optional "halitosis substudy" to investigate this issue by collecting some extra PK blood samples.

Study with completed results acquired from Horizon in 2024.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

INCLUSION CRITERIA: * Male or female with a documented diagnosis of cystinosis * On a stable dose of Cystagon® at least 21 days prior to Screening * WBC cystine level \> 1 nmol 1/2 cystine/mg of protein, on average over at least 2 measurements collected during the 2 years prior to Screening * No clinically significant change in liver function tests, i.e. 1.5 times upper limit of normal (ULN) for alanine aminotransferase and aspartate aminotransferase, 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/1.73m\^2 (using the equation from Schwartz 2009 J Am Soc Nephrol 20:629-647) * Female subjects 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), intrauterine device, or a partner who has been vasectomized for at least 6 months. * Subject or their parent or guardian must provide written informed consent, assent (where applicable), prior to participation in the study EXCLUSION CRITERIA: * Younger than 12 years of age * 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 \< 9 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 cysteamine and penicillamine * Female subjects who are nursing, planning a pregnancy, or are known or suspected to be pregnant * Subjects who, in the opinion of the investigator, are not able or willing to comply with study requirements.

Locations (14)

California Pacific Medical Center (CPMC) Research Institute

San Francisco, California, United States

Stanford University Medical School

Stanford, California, United States

Emory Children's Center

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Baylor College of Medicine / Texas Childrens Hospital

Houston, Texas, United States

University Hospital of Leuven

Leuven, Belgium

Hospices Civils de Lyon

Lyon, France

Hôpital Necker-Enfants Malades

Paris, France

Hôpital Robert Debré

Paris, France

Ospedale Pediatrico Bambino Gesù

Rome, Italy

...and 4 more locations

Outcomes

Primary Outcomes

Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values

The primary analysis of WBC cystine was performed using the natural log transformed WBC cystine level; the log transformation is a normalizing transformation. For each participant, the difference between the morning and corresponding non-morning log WBC cystine value (non-morning minus morning) at each monthly visit during the Cystagon® phase (Months 1, 2, and 3) was computed and these differences were averaged. The average difference between morning and non-morning log WBC cystine value was similarly computed for each participant during the RP103 phase (Months 5, 6, and 7). The primary analysis compared within-subject pairs (Cystagon® phase paired with RP103 phase) of non-morning minus morning average differences of log WBC cystine level.

Time frame: While taking Cystagon® (Months 1, 2, 3): within 15 minutes pre-morning (AM) and pre-non AM dose. During 3 months of RP103 (Months 5, 6, 7): 30 minutes post-AM and post-evening (PM) dose.

Secondary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs

AE: any untoward medical occurrence that does not necessarily have a causal relationship with study drug. SAE: any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is medically significant, and though not included in the above list, is an important medical event, according to the Investigator. Treatment-emergent adverse events (TEAEs) occurred after first dose of study drug. Clinically significant abnormalities in laboratory values (hematology, blood chemistry, urinalysis), electrocardiograms (ECGs), vital signs, and physical examinations were to be reported as adverse events and so are included in this summary of TEAEs

Time frame: From first dose of study drug to 7 days after last dose. Median duration of exposure was 91 days (range 82-108) for Cystagon® phase, 119 days (range 98-137) for the RP103 phase, and 861 days (range 30 - 1350) during the long-term RP-103 phase.

Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine

Participants who reported halitosis ("bad breath") as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of dimethylsulfide (DMS) in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state pharmacokinetic (PK) samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.

Time frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose

Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine

Participants who reported halitosis ("bad breath") as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.

Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine

Halitosis Substudy: Expired Air DMS Concentrations

Time frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose 30 min post-dose, 2, 3, 4 and 6 hours post-dose. While taking RP103 (Month 4, 5, or 7): Within 15 min. prior to morning dose. 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose