A Safety, Tolerability and Efficacy Study of VRDN 001 in Healthy Volunteers and Persons With Thyroid Eye Disease (TED)
Study Details
Study Description
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 |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0 [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 [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
- Change from baseline in measurement of proptosis as determined by exophthalmometer [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 [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 [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 [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) [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.
- Change from baseline in Subjective Diplopia Score [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.
- Change from baseline in Graves Orbitopathy-Quality of Life (GO-QoL) combined score [Up to Week 12 for MAD TED subjects, and up to Week 52 for extension study subjects]
Other Outcome Measures
- VRDN-001 concentrations in the blood over time [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 [Up to Day 50 for MAD subjects and up to Week 25 for extension study subjects]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Private Office of Raymond Douglas, MD, PhD | Beverly Hills | California | United States | 90210 |
| 2 | Byers Eye Institute/Stanford University | Palo Alto | California | United States | 94303 |
| 3 | Senta Clinic | San Diego | California | United States | 95207 |
| 4 | University of Colorado - Department of Ophthalmology | Aurora | Colorado | United States | 80045 |
| 5 | University of Florida Bascom Palmer Eye Center | Miami | Florida | United States | 33136 |
| 6 | Sarasota Retina Institute | Sarasota | Florida | United States | 34239 |
| 7 | Massachusetts Eye and Ear | Boston | Massachusetts | United States | 02114 |
| 8 | Michigan State University - Department of Neurology and Ophthalmology | East Lansing | Michigan | United States | 48824 |
| 9 | University of Minnesota Eye Clinic | Minneapolis | Minnesota | United States | 55455 |
| 10 | TKL Research, Inc. | Fair Lawn | New Jersey | United States | 07410 |
| 11 | Rutgers New Jersey Medical School - Department of Ophthalmology & Visual Science | Newark | New Jersey | United States | 07103 |
| 12 | Duke Eye Center | Durham | North Carolina | United States | 22710 |
| 13 | UPMC Eye Center | Pittsburgh | Pennsylvania | United States | 15213 |
| 14 | Neuro-Eye Clinical Trials | Bellaire | Texas | United States | 77401 |
| 15 | Baylor College of Medicine - Alkek Eye Center | Houston | Texas | United States | 77030 |
| 16 | University of Washington - Department of Ophthalmology | Seattle | Washington | United States | 98104 |
| 17 | Marshall Health | Huntington | West Virginia | United States | 25701 |
Sponsors and Collaborators
- Viridian Therapeutics, Inc.
Investigators
- Study Director: Barrett Katz, MD, MBA, Viridian Therapeutics, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VRDN-001-101