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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 : April 22, 2024
Sponsor:
Information provided by (Responsible Party):
Viridian Therapeutics, Inc.

Study Description
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Brief Summary:

Please note that Phase 1/2 (HV & MAD) cohort - recruitment is completed and Phase 3 Component (THRIVE) - is actively recruiting.

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 Phase 1/2 MAD (HV and TED) Drug: VRDN-001 Phase 3 Cohort (THRIVE) Drug: VRDN-001 Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 154 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 (HV(s) and Participants With Thyroid Eye Disease (TED)
Actual Study Start Date : December 3, 2021
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1/2 MAD (HV and TED)
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 Phase 1/2 MAD (HV and TED)
2 Infusions of multiple ascending doses of VRDN-001, ranging from 3 mg/kg to 20 mg/kg
Experimental: Phase 3 Cohort (THRIVE)
Participants with TED will be randomized to either VRDN-001 10mg/kg or placebo.
 Drug: VRDN-001 Phase 3 Cohort (THRIVE)
5 Infusions of VRDN-001 10mg/kg

Drug: VRDN-001 Placebo
5 Infusions of VRDN-001 placebo


Outcome Measures
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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 the Phase 3 study subjects ]
  2. Proptosis responder rate [ Time Frame: Week 6 for MAD TED participants, and Week 15 for Phase 3 study subjects ]
    Proportion of TED participants with a reduction of proptosis of ≥ 2 mm from baseline as determined by exophthalmometer


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 Phase 3 subjects ]
  2. Change from baseline in volume of orbital fat as determined by MRI [ Time Frame: Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects ]
  3. Change from baseline in volume of extraocular muscles as determined by MRI [ Time Frame: Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects ]
  4. Change from baseline in facial fat volume as determined by MRI [ Time Frame: Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects ]
  5. Change from baseline in Clinical Activity Score (CAS) [ Time Frame: Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 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 participants, and up to Week 52 for Phase 3 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 participants, and up to Week 52 for Phase 3 subjects ]
  8. Change in measurement of proptosis by MRI/CT [ Time Frame: Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects ]

Other Outcome Measures:
  1. VRDN-001 concentrations in the blood over time [ Time Frame: Up to Day 155 for MAD participants and up to Week 22 for Phase 3 subjects ]
  2. Incidence of anti-drug antibody (ADA) development in VRDN-001-treated subjects over time [ Time Frame: Up to Day 155 for MAD participants and up to Week 22 for Phase 3 subjects ]

Eligibility Criteria
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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 earing impairment

Key Inclusion Criteria for Participants with TED in Phase 1/2 MAD cohorts:

  • Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 1 year prior to screening OR moderate to severe chronic TED with documented evidence of ocular symptoms or signs that began over 1 year prior to screening
  • Must have active TED and a Clinical Activity Score (CAS) of ≥ 4 on the 7-item scale for the study (more proptotic) eye OR chronic TED with no CAS requirement
  • 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 in Phase 1/2 MAD cohorts:

  • 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 Must not have 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

Key Inclusion Criteria for Participants with TED in Phase 3 study:

  • Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 15 months prior to screening
  • Must have Clinical Activity Score (CAS) of ≥ 3 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 in Phase 3 study:

  • Must not have received prior treatment with another anti-IGF-1R monoclonal antibody
  • Must not have used oral corticosteroids within 2 weeks prior to Day 1
  • Must not have received rituximab, tocilizumab or other immunosuppressive agents within 8 weeks prior to Day 1
  • Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the Investigator would confound interpretation of the study results
  • Must not have had previous orbital irradiation or surgery for TED in the study eye
  • Must not have a history inflammatory bowel disease
  • Must not have a history or screening audiometry assessment of clinically significant (as determined by investigator) ear pathology, relevant ear surgery, or hearing l loss
  • Must not have received an investigational agent for any condition
  • Female TED participants must not be pregnant or lactating
Contacts and Locations
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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: Viridian Therapeutics 617-272-4609 viridian-clinical-trials@viridiantherapeutics.com

Locations
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Sponsors and Collaborators
Viridian Therapeutics, Inc.
Investigators
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Study Director: Barrett Katz, MD, MBA Viridian Therapeutics, Inc.
More Information
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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: April 22, 2024
Last Verified: April 2024
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