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OT-58 as an Enzyme Therapy for Patients With Cystathionine Beta-Synthase Deficient Homocystinuria (CBSDH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03406611
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : December 9, 2019
Information provided by (Responsible Party):
Orphan Technologies Ltd

Brief Summary:

Cystathionine Beta-Synthase (CBS) Deficient Homocystinuria (CBSDH) is a rare autosomal-recessive metabolic condition characterized by an excess of homocysteine (Hcy) in the plasma, tissues and urine. It is due to reduced or absent activity of the Cystathionine Beta-Synthase (CBS) enzyme, and is also known as classical homocystinuria. The symptoms associated with CBSDH are variable in severity and time of onset across patients. Some affected individuals may have mild signs of the disorder; others may have multi-systemic involvement including potentially life-threatening complications. CBSDH can affect many different organ systems of the body; the four most commonly involved are the eyes, central nervous system, skeleton, and the vascular system.

The current approaches to treatment of CBSDH patients include a highly restrictive diet and use of dietary supplements. Lifetime compliance with this diet is poor. OT-58 represents a novel therapeutic approach that incorporates the use of a modified version of the native, human CBS (hCBS) enzyme. The goal of treatment is to introduce the CBS enzyme into circulation, resulting in reduced Hcy levels, increased cystathionine levels and normalized cysteine (Cys) levels.

Condition or disease Intervention/treatment Phase
Homocystinuria Drug: OT-58 Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomized, Placebo-controlled, Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Effects on Clinical Outcomes of OT-58, Administered Subcutaneously in Patients With Cystathionine Beta-Synthase Deficient Homocystinuria (CBSDH).
Actual Study Start Date : January 22, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Arm Intervention/treatment
Active Comparator: Active drug Drug: OT-58
OT-58 sterile solution for subcutaneous injection
Other Name: OT-58 (PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS)

Placebo Comparator: Placebo Drug: Placebo
Normal saline for subcutaneous injection

Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 [Safety and Tolerability] [ Time Frame: through study completion, an average of 10 months ]

Secondary Outcome Measures :
  1. Changes in total plasma homocysteine in micromoles [ Time Frame: through study completion, an average of 10 months ]
  2. Changes in cognitive function using the National Institutes of Health (NIH) Toolbox Cognition Battery [ Time Frame: through study completion, an average of 10 months ]
  3. Eye assessments to evaluate ocular health: Visual acuity examination will be performed to determine the clarity or sharpness of vision [ Time Frame: through study completion, an average of 10 months ]
  4. Eye assessments to evaluate ocular health: Slit lamp eye examination will be performed to look for any diseases or abnormalities in the eye [ Time Frame: through study completion, an average of 10 months ]
  5. Dual-Energy X-Ray Absorptiometry (DEXA) to measure bone mineral density [ Time Frame: through study completion, an average of 10 months ]
  6. Patient-Reported Outcomes Measurement Information System (Neuro-QoL) to measure patient well being [ Time Frame: through study completion, an average of 10 months ]
  7. Quality of life measures by EQ-5D questionnaire [ Time Frame: through study completion, an average of 10 months ]
  8. Quality of life measures by SF-36 questionnaire [ Time Frame: through study completion, an average of 10 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed diagnosis of CBSDH based on genetic confirmation and plasma tHcy ≥80 micromoles
  • Willing and able to provide written, signed informed consent and to comply with all study related procedures
  • Females of child-bearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study
  • Sexually active patients must be willing to use acceptable method of contraception while on the study and for 4 weeks after the end of study
  • Willing to maintain a stable diet with no significant modifications while on study
  • In generally good health, except for possible complications of CBSDH.

Exclusion Criteria:

  • Use of any investigational product or investigational medical device within 30 days prior to Screening, or while on study
  • Use or planned use of any injectable drugs containing PEG including medroxyprogesterone (e.g. Depo-Provera) injection within 3 months prior to Screening and while on study
  • Known hypersensitivity to PEG-containing product or any components of OT-58
  • A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody
  • A history of organ transplantation, chronic immunosuppressive therapy, or substance abuse
  • Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study
  • Concurrent disease or condition or planned major surgery that would interfere with study participation or safety in the opinion of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03406611

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Contact: Anne Kuan +1 781 966 3832

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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
United States, Indiana
Indiana University School of Medicine Recruiting
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Orphan Technologies Ltd
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Responsible Party: Orphan Technologies Ltd Identifier: NCT03406611    
Other Study ID Numbers: CBS-HCY-CT-01
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: December 9, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Connective Tissue Diseases
Metabolic Diseases