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A Safety, Tolerability and Efficacy Study of VRDN 001 in Healthy Volunteers and Persons With Thyroid Eye Disease (TED)

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ClinicalTrials.gov Identifier: NCT05176639
Recruitment Status : Recruiting
First Posted : January 4, 2022
Last Update Posted : June 13, 2022
Sponsor:
Information provided by (Responsible Party):
Viridian Therapeutics, Inc.

Brief Summary:
The investigational drug, VRDN-001, is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in patients with thyroid eye disease (TED). This clinical trial will evaluate the safety, tolerability and pharmacokinetics (the concentration of drug in the blood over time) of VRDN-001 in healthy volunteers and in patients with TED. Study participants with TED will also be evaluated over time for changes in their signs and symptoms of TED compared to their baseline measurements.

Condition or disease Intervention/treatment Phase
Thyroid Eye Disease Drug: VRDN-001 Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multiple Ascending Dose (MAD) Safety, Tolerability and Efficacy Study of VRDN 001, a Humanized Monoclonal Antibody Directed Against the IGF-1 Receptor, in Normal Healthy Volunteers (NHVs) and Subjects With Thyroid Eye Disease (TED)
Actual Study Start Date : December 3, 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 MAD study part
Healthy participants and participants with TED will be randomized to receive two intravenous infusions of VRDN-001 or placebo with an interval of 3 weeks.
Drug: VRDN-001
Multiple ascending doses of VRDN-001, ranging from 3 mg/kg to 20 mg/kg

Drug: Placebo
Multiple doses of placebo

Experimental: Phase 2 extension study part
Participants with TED will be randomized to one of two VRDN-001 doses/dosing regimens or placebo. The doses/dosing regimens may include doses up to 20 mg/kg with the dosing interval and duration to be defined based on the results of the MAD study part.
Drug: VRDN-001
Multiple doses of VRDN-001 using dosing regimen 1

Drug: VRDN-001
Multiple doses of VRDN-001 using dosing regimen 2

Drug: Placebo
Multiple doses of placebo




Primary Outcome Measures :
  1. Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to Day 50 for MAD healthy volunteers, up to Day 169 for MAD TED subjects, and up to Week 52 for extension study subjects ]
  2. Proptosis responder rate [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 24 for extension study subjects ]
    Proportion of TED subjects with a reduction of proptosis of ≥ 2 mm from baseline


Secondary Outcome Measures :
  1. Change from baseline in measurement of proptosis as determined by exophthalmometer [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]
  2. Change from baseline in volume of orbital fat as determined by MRI [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]
  3. Change from baseline in volume of extraocular muscles as determined by MRI [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]
  4. Change from baseline in facial fat volume as determined by MRI [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]
  5. Change from baseline in Clinical Activity Score (CAS) [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]
    Each of 7 clinical signs and symptoms of ocular inflammation is scored as present or absent (score of 1 or 0, respectively). The CAS is the sum of the individual scores (range from 0 to 7) where a higher score indicates a greater level of inflammation.

  6. Change from baseline in Subjective Diplopia Score [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]
    Diplopia grade is assessed using the Gorman Subjective Diplopia Score (range from 0 to 3) based on verbal responses by the study subject. A higher score indicates a worse diplopia grade.

  7. Change from baseline in Graves Orbitopathy-Quality of Life (GO-QoL) combined score [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]

Other Outcome Measures:
  1. VRDN-001 concentrations in the blood over time [ Time Frame: Up to Day 50 for MAD subjects and up to Week 25 for extension study subjects ]
  2. Incidence of anti-drug antibody (ADA) development in VRDN-001-treated subjects over time [ Time Frame: Up to Day 50 for MAD subjects and up to Week 25 for extension study subjects ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria for Healthy Volunteers:

  • Must be free of clinically significant disease or medical conditions as determined by the Investigator
  • Female volunteers must not be of child-bearing potential

Key Exclusion Criteria for Healthy Volunteers:

• Must not have a history of or any evidence of diabetes mellitus, recently diagnosed renal impairment or inflammatory bowel disease, or clinically significant ear pathology or hearing impairment

Key Inclusion Criteria for Participants with TED:

  • Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 1 year prior to screening
  • Must have Clinical Activity Score (CAS) of ≥ 4 on the 7-item scale for the study (more proptotic) eye
  • Must agree to use highly effective contraception as specified in the protocol
  • Female TED participants must have a negative serum pregnancy test

Key Exclusion Criteria for Participants with TED:

  • Must not have received prior treatment with another anti-IGF-1R monoclonal antibody
  • Must not have used oral corticosteroids within 4 weeks prior to Day 1
  • Must not have received rituximab, tocilizumab or other immunosuppressive agents within 90 days prior to Day 1
  • Must not have evidence of optic nerve involvement within the previous 6 months
  • Must not have corneal decompensation in the study eye unresponsive to medical management
  • Must not have had previous orbital irradiation or surgery for TED in the study eye
  • Must not have a history inflammatory bowel disease, or clinically significant ear pathology or hearing impairment
  • Must not have received an investigational agent for any condition within 60 days
  • Female TED participants must not be pregnant or lactating

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 ClinicalTrials.gov identifier (NCT number): NCT05176639


Contacts
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Contact: VP, Clinical Operations 617-272-4609 viridian-clinical-trials@viridiantherapeutics.com

Locations
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United States, California
The Private Office of Raymond Douglas, MD, PhD Recruiting
Beverly Hills, California, United States, 90210
Senta Clinic Recruiting
San Diego, California, United States, 95207
United States, Colorado
University of Colorado - Department of Ophthalmology Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Sarasota Retina Institute Recruiting
Sarasota, Florida, United States, 34239
United States, Michigan
Michigan State University - Department of Neurology and Ophthalmology Recruiting
East Lansing, Michigan, United States, 48824
United States, New Jersey
TKL Research, Inc. Recruiting
Fair Lawn, New Jersey, United States, 07410
Rutgers New Jersey Medical School - Department of Ophthalmology & Visual Science Recruiting
Newark, New Jersey, United States, 07103
United States, Texas
Neuro-Eye Clinical Trials Recruiting
Bellaire, Texas, United States, 77401
Baylor College of Medicine - Alkek Eye Center Recruiting
Houston, Texas, United States, 77030
United States, Washington
University of Washington - Department of Ophthalmology Recruiting
Seattle, Washington, United States, 98104
United States, West Virginia
Marshall Health Recruiting
Huntington, West Virginia, United States, 25701
Sponsors and Collaborators
Viridian Therapeutics, Inc.
Investigators
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Study Director: Barrett Katz, MD, MBA Viridian Therapeutics, Inc.
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Responsible Party: Viridian Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05176639    
Other Study ID Numbers: VRDN-001-101
First Posted: January 4, 2022    Key Record Dates
Last Update Posted: June 13, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Viridian Therapeutics, Inc.:
Graves Ophthalmopathy
Thyroid Eye Disease
Thyroid-Associated Ophthalmopathy
Dysthyroid Ophthalmopathy
Graves Eye Disease
Graves Orbitopathy
Myopathic Ophthalmopathy
Congestive Ophthalmopathy
Edematous Ophthalmopathy
Infiltrative Ophthalmopathy
Additional relevant MeSH terms:
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Eye Diseases
Graves Ophthalmopathy
Thyroid Diseases
Endocrine System Diseases
Eye Diseases, Hereditary
Graves Disease
Exophthalmos
Orbital Diseases
Genetic Diseases, Inborn
Goiter
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases