Clinical Trials for Urea Cycle Disorders

In addition to the studies being conducted by the Urea Cycle Disorders Consortium, the following is list of clinical trials sponsored by biotherapeutic or pharmaceutical companies for urea cycle disorders. For more trial information and specific eligibility criteria, click on the link for each study. For information about how clinical trials are conducted, see About Clinical Trials below.

CLINICAL TRIALS FOR INVESTIGATIONAL DRUG, HPN-100 (Sponsored by Hyperion Therapeutics)

BACKGROUND:  Many UCD families and patients have experienced major difficulties with administration (giving the drug), compliance (tolerating the daily regimen) or tolerance of side effects of Buphenyl® (sodium phenylbutyrate). An investigational drug, related to Buphenyl® in chemical structure, is being studied for use in urea cycle disorders. This investigational drug, called HPN-100, is a nearly tasteless, odorless liquid formulation which is intended to work similarly to Buphenyl in removing ammonia, but without the pill burden or need to mask taste. Three teaspoons of HPN-100 equals approximately 40 tablets of sodium phenylbutyrate. The sponsor of the trial, Hyperion Therapeutics, will provide HPN-100 free of charge to trial participants and cover the costs of laboratory tests and physician visits associated with the trial, as well as reasonable travel expenses to a trial location.

CURRENTLY RECRUITING! PHASE 2 Study of the Safety, Pharmacokinetics and Efficacy of HPN-100 in Pediatric Subjects with Urea Cycle Disorders (UCD)

Sponsor: Hyperion Therapeutics

Purpose: This study (HPN-100-012) will enroll approximately 20 pediatric subjects, ages 29 days old to less than 6 years of age with UCD (all subtypes except NAGS deficiency) currently treated with BUPHENYL® for at least 5 days prior to enrollment.  The study includes both a 10 day ‘switch-over’ phase from BUPHENYL to HPN-100, involving two overnight stays, and a one-year safety follow-up phase. Approximately 12 patients will be enrolled into the ‘switch over’ phase of the study before entering the one-year safety phase.  The sponsor may decide to enroll an additional 8 subjects directly into the one-year safety study following complete recruitment of the switch-over phase.  Patients who enroll in the one-year safety study (only) will receive HPN-100 and return for a study visit one week later.  Visits during the one-year safety phase for all patients will occur monthly for 3 months and then quarterly thereafter. Your physician will make the final decision whether or not your child is medically eligible based on child's age, UCD type, and medical history.

Trial Locations:

Baylor College of Medicine: Principal investigator Brendan Lee, M.D., Ph.D.

Univ. of MN: Principal Investigator Susan Berry, M.D.

Children's National Medical Center: Principal Investigator Uta Lichter, M.D.

Mt. Sinai Medical Center: Principal Investigator George Diaz, M.D.

UCLA: Principal Investigator Derek Wong, M.D.

Rainbow Babies, Cleveland: Principal Investigator Shawn McCandless, M.D.

Maine Medical, Portland: Principal Investigator Wendy Smith, M.D.

Oregon Health Sciences: Principal Investigator Cary Harding, M.D.

FULLY RECRUITED! PHASE 2 Study of the Safety and Tolerability of HPN-100 compared to Sodium Phenylbutyrate in Children Aged 6-17 Years with Urea Cycle Disorders, with Long Term Safety Extension.

Sponsor: Hyperion Therapeutics

Purpose: This protocol (HPN-100-005) is the first study of HPN-100 in pediatric subjects with urea cycle disorders. The initial study was designed to assess the safety of HPN-100 and its ability to control blood ammonia as compared with sodium phenylbutyrate. After a two week controlled period, all participants received HPN-100 in a 12-month safety study.

Trial Locations:

UCLA: Principal Investigator: Stephen Cederbaum, MD

Children's National Medical Center: Principal Investigator: Uta Lichter, MD

Mount Sinai School of Medicine NY: Principal Investigator: George Diaz, MD 

Seattle Children's Hospital: Principal Investigator: Lawrence Merritt, MD

Children's Hospital of Wisconsin, Milwaukee:  Principal Investigator: William Rhead, MD

The Hospital for Sick Children, Toronto, Ontario, Canada:Principal Investigator: Annette Feigenbaum, MD  

FULLY RECRUITED! PHASE 3 Study of the Efficacy and Safety of HPN-100 for the Treatment of Adults with Urea Cycle Disorders.

Sponsor: Hyperion Therapeutics

Purpose: This protocol (HPN-100-006) is a randomized, active-controlled, double-blind, cross-over study in subjects with UCD who are currently being treated with sodium phenylbutyrate. Subjects will be randomly assigned to receive either HPN-100 plus sodium phenylbutyrate placebo, or sodium phenylbutyrate and a placebo of HPN-100 for two weeks, and then crossed over to receive the other treatment for two weeks. Subjects who complete this study and meet entry criteria will be offered the opportunity to enroll in the twelve-month open-label safety study of HPN-100.

Trial Locations:

FULLY RECRUITED! PHASE 3 Study of the Safety of HPN-100 for the Long-Term Treatment of Urea Cycle Disorders.

Sponsor: Hyperion Therapeutics

Purpose: This protocol (HPN-100-007)is a long-term safety study of HPN-100 in patients 18 years and older with urea cycle disorder. Subjects will be assessed regularly for safety and control of blood ammonia.  Hyperammonemic events will be characterized with respect to contributing factors such as intercurrent illness, diet, and noncompliance with medication.

Trial Locations: See Locations for Phase 3 Study of the Efficacy and Safety of HPN-100 for the Treatment of Adults with Urea Cycle Disorders

STUDY OF THE SAFETY AND EFFICACY OF INFUSION OF HUMAN HETEROLOGOUS LIVER CELLS IN CHILDREN WITH UREA CYCLE DISORDERS (SELICAIII)

Sponsor: Cytonet GmbH & Co. KG

BACKGROUND: In the last years, orthotopic liver transplantation (OLT) has become a therapeutic option for neonatal-onset and severe UCD. However, in the first weeks of life OLT still is technically demanding and prone to complications. With larger size of the recipient, the technical problems with OLT decrease considerably. The increased body weight usually achieved at the age of more than 8 weeks is related to a major reduction in transplantation related morbidity. Stabilization of metabolism until the patient can undergo OLT is essential. In this study, young children with UCD will be treated by repetitive application of human liver cells. The aim of this new therapy option is to supply a sufficient amount of healthy liver cells to compensate for the metabolic defect and to reduce the risk of neurological deterioration while awaiting OLT. This is a Phase II clinical trial to study the safety and effectiveness of this treatment.

About Clinical Trials

What is a clinical trial?

A clinical trial is a study to determine whether a treatment improves a clinical condition or a disease.  A clinical trial is an "experiment" which is the most rigorous type of study. The protocol for the study is designed to test the specific idea that a treatment is effective and safe. Each study must be approved and monitored by an independent committee of physicians, statisticians and members of the community called an Institutional Review Board (IRB). The IRB ensures that risks are acceptably small and in relationship to potential benefits.

Participating in clinical trials offers many opportunities to learn more about treatments and disease. However, it is important to have a good understanding of the risks and benefits of any study when making a decision to participate.

Many individuals question why they should consider participating in a clinical trial, what it is like to participate in a clinical trial and what they should expect. An individual’s decision to enter a clinical trial is a very personal one and there are a variety of reasons for considering taking part in a study. Having hope for a future cure, greater understanding of their own illness, feeling better and contributing to research and society are some personal reasons participants choose to enter trials. Participants in clinical trials may also receive new treatments before they are readily available to nonparticipants.

What are the phases of clinical trials?

Clinical trials are conducted in phases. In orphan diseases like urea cycle disorders, trial size is smaller than the average numbers presented below due to the limited patient population.  Each phase has a specific purpose and answers different questions:

Phase I Trials: An experimental drug or treatment is tested in a very small group of people (20-80) to evaluate its safety, determine a safe dosage range, and identify side effects. This is a safety study.

Phase II Trials: The experimental drug or treatment is now given to a larger group of people (100-300) to determine its efficacy (whether it does what it is supposed to do) and to further evaluate its safety.

Phase III Trials: The experimental drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, and to collect information that will allow the drug or treatment to be used safely.

Phase IV Trials: These are post-marketing trials, usually conducted by the pharmaceutical company after the drug receives FDA approval and has been made available to the public.  These studies collect additional information on the drug's risks, benefits and optimal uses.

Who can participate in a clinical trial?

All clinical trials have specific guidelines about who is eligible to participate. Some studies seek participants with illnesses or conditions, while others require healthy volunteers.

Who sponsors clinical trials?

Clinical trials are often funded by pharmaceutical companies to test new drugs. However, other funders of clinical trials are researchers, individuals, medical institutions, nonprofit organizations, foundations, voluntary health organizations, as well as federal agencies like the National Institutes of Health (NIH).

Where can I ask questions or find more information about the clinical trials for urea cycle disorders?

Contact Cindy Le Mons, Executive Director of the National Urea Cycle Disorders Foundation (626)578-0833. The Foundation is here to support you and answer any questions you may have about the trials or about how to participate in a trial. ((Please note that information supplied about industry-sponsored clinical trials does not imply endorsement by NUCDF).

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