Phase 3 Study of Cysteamine Bitartrate Delayed-release (RP103) Compared to Cystagon® in Patients With Cystinosis

A Randomized, Crossover Pharmacokinetic and Pharmacodynamic Study to Determine the Safety and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103), Compared to Cystagon® in Patients With Nephropathic Cystinosis

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) which must be taken every six hours for the rest of the patient's life to prevent complications of cystinosis. RP103 is a formulation of cysteamine bitartrate that is being studied to see if it may be able to be given less frequently, once every 12 hours, and have similar results to four times a day Cystagon®.

Study Overview

• Status: Completed
• Conditions: Cystinosis
• Intervention / Treatment: Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103); Drug: Cystagon® (Cysteamine Bitartrate)

Detailed Description

This is a multi-center, open-label, randomized, cross-over study to determine whether steady-state, twice a day treatment with Cysteamine Bitartrate Delayed-release Capsules(RP103) results in comparable depletion of white blood cell (WBC) cystine levels compared to the existing four times a day cysteamine treatment. It will involve up to 20 clinic visits plus intermittent home use of the RP103. Most of these clinic visits occur in clusters of 3-4 consecutive days. Eligible patients will be offered enrollment into a long-term follow up study.

Study with completed results acquired from Horizon in 2024.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • Hospices Civils de Lyon
  • Montpellier, France
    • Villeneuve-Lapeyronie Hospital
  • Paris, France
    • Necker Hospital
  • Paris, France
    • Robert Debre Hospital
• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Center
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical School
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Children's Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female subjects must have nephropathic cystinosis.
• Subjects must be on a stable dose of Cystagon® sufficient to maintain their white blood cell (WBC) cystine level at ≤ 1.0 nmol/half-cystine/mg protein.
• Subjects must be able to swallow their typically administered Cystagon® capsule with the capsule intact.
• Within the last 6 months, no clinically significant change in liver function [i.e., ALT, AST, total bilirubin] and renal function [i.e., estimated GFR] at Screening as determined by the Investigator.
• Subjects with an estimated GFR (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 or their parent or guardian must provide written informed consent and assent (where applicable) prior to participation in the study.

Exclusion Criteria:

• Subject's age < 6 years old or subject's weight < 21 kg.
• 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, 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 receiving any form of cysteamine medication through a gastric tube.
• Subjects who are receiving maintenance dialysis or who have had a kidney transplant.
• Subjects who are on an active kidney transplant list or who are planning to receive a kidney transplant within 3 months of Screening.
• 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 have a made a blood donation within 30 days of Screening.
• Subjects who, in the opinion of the Investigator, are not able or willing to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RP103 Q12H	Drug: Cysteamine Bitartrate Delayed-release Capsules (RP103); Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1: Every 12H, supplied in 75 and 25mg capsules/Duration of Treatment: 3 weeks
Active Comparator: Cystagon® Q6H	Drug: Cystagon® (Cysteamine Bitartrate); Run-in Period (Weeks 1, 2, 3) and Period 1 (Weeks 4, 5, 6) or Period 2 (Weeks 7, 8, 9); Immediate crossover to opposite treatment than taken during Period 1: Every 6H, supplied in 150 and 50mg capsules/Duration of Treatment: 3 weeks each period used

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Steady-state White Blood Cell Cystine Levels of RP103 Compared to Cystagon®	4 weeks after the last subject has completed the study

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of Cysteamine PK Profiles, Steady State Cmax, Between RP103 and Cystagon®.	4 weeks after the last subject has completed the study
Comparison of Cysteamine PK Profiles, Steady State Tmax, Between RP103 and Cystagon®.	4 weeks after the last subject has completed the study
Comparison of Cysteamine PK Profiles, AUC(0-t), Between RP103 and Cystagon®.	6 hours post dosing for Cystagon®; 12 hours post dosing for RP103.

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• RP103 (marketed as PROCYSBI) is now approved by the US FDA for management of nephropathic cystinosis in patients 6 years and older

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: October 22, 2009
• First Submitted That Met QC Criteria: October 22, 2009
• First Posted (Estimated): October 23, 2009

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: metabolic disease; cystinosis; orphan disease; cysteamine; inheritable disease; CTNS protein, human; nephropathic cystinosis
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lysosomal Storage Diseases; Cystinosis; Molecular Mechanisms of Pharmacological Action; Cystine Depleting Agents; Cysteamine
• Other Study ID Numbers: RP103-03