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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05176639




Registration number
NCT05176639
Ethics application status
Date submitted
15/12/2021
Date registered
4/01/2022

Titles & IDs
Public title
A Safety, Tolerability and Efficacy Study of VRDN 001 in Healthy Volunteers and Persons With Thyroid Eye Disease (TED)
Scientific 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)
Secondary ID [1] 0 0
VRDN-001-101
Universal Trial Number (UTN)
Trial acronym
THRIVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thyroid Eye Disease 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - VRDN-001 Phase 1/2 MAD (HV and TED)
Treatment: Drugs - VRDN-001 Phase 3 Cohort (THRIVE)
Treatment: Drugs - VRDN-001 Placebo

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.

Experimental: Phase 3 Cohort (THRIVE) - Participants with TED will be randomized to either VRDN-001 10mg/kg or placebo.


Treatment: Drugs: 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

Treatment: Drugs: VRDN-001 Phase 3 Cohort (THRIVE)
5 Infusions of VRDN-001 10mg/kg

Treatment: Drugs: VRDN-001 Placebo
5 Infusions of VRDN-001 placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Proptosis responder rate
Timepoint [2] 0 0
Week 6 for MAD TED participants, and Week 15 for Phase 3 study subjects
Secondary outcome [1] 0 0
Change from baseline in measurement of proptosis as determined by exophthalmometer
Timepoint [1] 0 0
Up to Week 12 for MAD TED subjects, and up to Week 52 for Phase 3 subjects
Secondary outcome [2] 0 0
Change from baseline in volume of orbital fat as determined by MRI
Timepoint [2] 0 0
Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary outcome [3] 0 0
Change from baseline in volume of extraocular muscles as determined by MRI
Timepoint [3] 0 0
Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary outcome [4] 0 0
Change from baseline in facial fat volume as determined by MRI
Timepoint [4] 0 0
Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary outcome [5] 0 0
Change from baseline in Clinical Activity Score (CAS)
Timepoint [5] 0 0
Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary outcome [6] 0 0
Change from baseline in Subjective Diplopia Score
Timepoint [6] 0 0
Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary outcome [7] 0 0
Change from baseline in Graves Orbitopathy-Quality of Life (GO-QoL) combined score
Timepoint [7] 0 0
Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects
Secondary outcome [8] 0 0
Change in measurement of proptosis by MRI/CT
Timepoint [8] 0 0
Up to Week 12 for MAD TED participants, and up to Week 52 for Phase 3 subjects

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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 systemic 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 systemic 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2025
Actual
Sample size
Target
154
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
North Shore Private Hospital - Saint Leonards
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Colorado
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United States of America
State/province [3] 0 0
Florida
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United States of America
State/province [4] 0 0
Georgia
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United States of America
State/province [5] 0 0
Massachusetts
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United States of America
State/province [6] 0 0
Michigan
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United States of America
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Minnesota
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United States of America
State/province [8] 0 0
Missouri
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United States of America
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New Jersey
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United States of America
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North Carolina
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United States of America
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Pennsylvania
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United States of America
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Texas
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Utah
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United States of America
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Washington
Country [15] 0 0
United States of America
State/province [15] 0 0
West Virginia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
France
State/province [17] 0 0
Angers
Country [18] 0 0
France
State/province [18] 0 0
Montpellier
Country [19] 0 0
France
State/province [19] 0 0
Saint-Herblain
Country [20] 0 0
Germany
State/province [20] 0 0
Berlin
Country [21] 0 0
Germany
State/province [21] 0 0
Dresden
Country [22] 0 0
Germany
State/province [22] 0 0
Göttingen
Country [23] 0 0
Italy
State/province [23] 0 0
Milan
Country [24] 0 0
Netherlands
State/province [24] 0 0
Amsterdam
Country [25] 0 0
Netherlands
State/province [25] 0 0
Rotterdam
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Spain
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Córdoba
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Spain
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Madrid
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Spain
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Sevilla
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Spain
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Valence
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Spain
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Zaragoza
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Turkey
State/province [31] 0 0
Pendik
Country [32] 0 0
Turkey
State/province [32] 0 0
Yenimahalle
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Bristol
Country [34] 0 0
United Kingdom
State/province [34] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Viridian Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Barrett Katz, MD, MBA
Address 0 0
Viridian Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05176639