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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.
 
ClinicalTrials.gov Identifier: NCT03406611
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : December 9, 2019
Sponsor:
Information provided by (Responsible Party):
Orphan Technologies Ltd

Tracking Information
First Submitted Date  ICMJE December 5, 2017
First Posted Date  ICMJE January 23, 2018
Last Update Posted Date December 9, 2019
Actual Study Start Date  ICMJE January 22, 2019
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2018)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2018)
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 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
  • Changes in total plasma homocysteine in micromoles [ Time Frame: through study completion, an average of 10 months ]
  • Changes in cognitive function using the National Institutes of Health (NIH) Toolbox Cognition Battery [ Time Frame: through study completion, an average of 10 months ]
  • 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 ]
  • 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 ]
  • Dual-Energy X-Ray Absorptiometry (DEXA) to measure bone mineral density [ Time Frame: through study completion, an average of 10 months ]
  • Patient-Reported Outcomes Measurement Information System (Neuro-QoL) to measure patient well being [ Time Frame: through study completion, an average of 10 months ]
  • Quality of life measures by EQ-5D questionnaire [ Time Frame: through study completion, an average of 10 months ]
  • Quality of life measures by SF-36 questionnaire [ Time Frame: through study completion, an average of 10 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2018)
  • Changes in total plasma homocysteine in micromolar [ Time Frame: through study completion, an average of 2 years ]
  • Changes in cognitive function using the National Institutes of Health (NIH) Toolbox Cognition Battery [ Time Frame: through study completion, an average of 2 years ]
  • 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 2 years ]
  • 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 2 years ]
  • Dual-Energy X-Ray Absorptiometry (DEXA) to measure bone mineral density [ Time Frame: through study completion, an average of 2 years ]
  • Patient-Reported Outcomes Measurement Information System (PROMIS) to measure patient well being [ Time Frame: through study completion, an average of 2 years ]
  • Quality of life measures by EQ-5D questionnaire [ Time Frame: through study completion, an average of 2 years ]
  • Quality of life measures by SF-36 questionnaire [ Time Frame: through study completion, an average of 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE OT-58 as an Enzyme Therapy for Patients With Cystathionine Beta-Synthase Deficient Homocystinuria (CBSDH)
Official Title  ICMJE 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).
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Homocystinuria
Intervention  ICMJE
  • Drug: OT-58
    OT-58 sterile solution for subcutaneous injection
    Other Name: OT-58 (PEG modified CBS, PEG htCBS C15S, htCBS C15S ME-200GS)
  • Drug: Placebo
    Normal saline for subcutaneous injection
Study Arms  ICMJE
  • Active Comparator: Active drug
    Intervention: Drug: OT-58
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 15, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anne Kuan +1 781 966 3832 anne.kuan@neovii.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03406611
Other Study ID Numbers  ICMJE CBS-HCY-CT-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Orphan Technologies Ltd
Study Sponsor  ICMJE Orphan Technologies Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Orphan Technologies Ltd
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP