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

• ClinicalTrials.gov Identifier: NCT05176639
• Recruitment Status: Active, not recruiting
• First Posted: January 4, 2022
• Last Update Posted: May 9, 2024
• Sponsor: Viridian Therapeutics, Inc.
• Information provided by (Responsible Party): Viridian Therapeutics, Inc.

Tracking Information

• First Submitted Date: December 15, 2021
• First Posted Date: January 4, 2022
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: December 3, 2021
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 25, 2023)

• 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 ]
• 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

Original Primary Outcome Measures (submitted: December 15, 2021)

• 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 ]
• 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

Current Secondary Outcome Measures (submitted: July 25, 2023)

• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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.
• 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.
• 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 ]
• 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 ]

Original Secondary Outcome Measures (submitted: December 15, 2021)

• Change from baseline in measurement of proptosis [ Time Frame: Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]

Current Other Pre-specified Outcome Measures (submitted: July 25, 2023)

• 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 ]
• 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 ]

Original Other Pre-specified Outcome Measures (submitted: December 15, 2021)

• 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 ]
• 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 ]

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Thyroid Eye Disease

Intervention

• 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
• Drug: VRDN-001 Phase 3 Cohort (THRIVE)
  5 Infusions of VRDN-001 10mg/kg
• Drug: VRDN-001 Placebo
  5 Infusions of VRDN-001 placebo

Study Arms

• 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.
  Intervention: Drug: VRDN-001 Phase 1/2 MAD (HV and TED)
• Experimental: Phase 3 Cohort (THRIVE)
  Participants with TED will be randomized to either VRDN-001 10mg/kg or placebo.
  Interventions:

  • Drug: VRDN-001 Phase 3 Cohort (THRIVE)
  • Drug: VRDN-001 Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 25, 2023): 154
• Original Estimated Enrollment (submitted: December 15, 2021): 76
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, France, Germany, Italy, Netherlands, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05176639
• Other Study ID Numbers: VRDN-001-101
• 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

• Plan to Share IPD: No

• Current Responsible Party: Viridian Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Viridian Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Barrett Katz, MD, MBA; Viridian Therapeutics, Inc.

• PRS Account: Viridian Therapeutics, Inc.
• Verification Date: May 2024