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

NCT01733316 | Completed Phase 3 Results

• 2 other identifiers: RP103-072012-002773-64
• Study Type: interventional
• Target: 41
• Locations: 6 countries
• Sites: 14

Brief Summary

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.

Conditions

Cystinosis

Keywords

Nephropathic Cystinosis; Cysteamine; Delayed-Release Cysteamine; Orphan Disease; CTNS Protein, Human

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (5)

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

  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

  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

  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

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

  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: Expired Air DMS Concentrations

  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

Study Arms (1)

All Participants

EXPERIMENTAL

Cystagon® Phase: From Screening and during Months 1, 2, 3 participants receive their usual dose of Cystagon® every 6 hours (Q6H). RP103 Phase: During Months 3.5, 4, 5, 6, 7 participants receive RP103 every 12 hours (Q12H). Long Term Phase: On or after Month 7, for the remainder of study participants receive RP103 Q12H.

Drug: RP103; Drug: Cystagon®

Interventions

RP103 DRUG

Also known as: cysteamine bitartrate delayed-release capsules, PROCYSBI®

All Participants

Cystagon® DRUG

Also known as: cysteamine bitartrate

All Participants

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (14)

California Pacific Medical Center (CPMC) Research Institute

San Francisco, California, 94115, United States

Location

Stanford University Medical School

Stanford, California, 94305, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

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

Chicago, Illinois, 60614, United States

Location

Baylor College of Medicine / Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

University Hospital of Leuven

Leuven, Belgium

Location

Hospices Civils de Lyon

Lyon, France

Location

Hôpital Necker-Enfants Malades

Paris, France

Location

Hôpital Robert Debré

Paris, France

Location

Ospedale Pediatrico Bambino Gesù

Rome, Italy

Location

Radboud University Nijmegen Medical Center

Nijmegen, Netherlands

Location

Queen Elizabeth Hospital Birmingham

Birmingham, United Kingdom

Location

Great Ormond Street

London, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 19158356 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Cystinosis; Rare Diseases

Interventions

Cysteamine

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Results Point of Contact

• Title: Evelyn Olson, Director
• Organization: Horizon Pharma USA, Inc.

clinicaltrials@horizonpharma.com

224-383-3000

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2012
• First Posted: November 27, 2012
• Study Start: January 31, 2013
• Primary Completion: February 1, 2015
• Study Completion: July 10, 2017
• Last Updated: December 27, 2024
• Results First Posted: May 24, 2017

Record last verified: 2024-12

Locations

IT (1); GB (3); BE (1); US (5); NL (1); FR (3)