An open-label study for participants who are non-responders at the end of treatment assessment on the VRDN-001-101 and VRDN-001-301 pivotal studies.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Viridian Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

25 Jun 2024 → 23 Jun 2025

Decision date (initial)

2024-04-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Viridian Therapeutics, Inc.

External identifiers

EU CT number

2023-507350-33-00

WHO UTN

U1111-1299-6499

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To provide open-label access of VRDN-001 to participants who were previously non-responders at 3 weeks post the fifth intravenous (IV) infusion in the VRDN-001-101 and VRDN-001-301 pivotal studies.
• To assess the safety and efficacy of VRDN-001 in participants who were previously treated with VRDN-001 or placebo.

Conditions and MedDRA coding

Thyroid eye disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Must be able to understand the study procedures and the risks involved and must provide written informed consent before the first study-related activity
2. Must Have completed at least 5 IV infusions and assessments required to determine proptosis responder status 3 weeks post the fifth IV infusion (i.e., Week 15) as defined in either the VRDN-001-101 or VRDN-001-301 pivotal studies
3. Must have Been a participant in either the VRDN-001-101 or VRDN-001-301 studies and found to be a non-responder as defined within the VRDN-001-101 or VRDN-001-301 study.
4. Must Not require immediate ophthalmological or orbital surgery in the study eye for any reason
5. If female, have a negative urine pregnancy test at Day 1 and further negative urine pregnancy tests immediately before each dose of study medication and following the last dose of study medication as described in Appendix 1. If the participant is a woman of childbearing potential (including those with <2 years since the onset of menopause or not surgically sterile by hysterectomy, bilateral salpingectomy or bilateral oophorectomy); such participants must continue to agree to use an acceptable method of contraception such as a condom and a second highly effective method of contraception as described in Section 4.4 from the Day 1 Visit up to and including 100 days after the last dose of study medication. If the participant is initiating hormonal contraception within one cycle of Day 1, participant agrees to use a double-barrier method of contraception until completing one-full cycle of hormonal contraception. An acceptable double-barrier combination method is a condom with either diaphragm or sponge with spermicide.
6. Must agree to continue (if not a surgically sterile male) to use an acceptable method of contraception such as a condom and a second highly effective method of contraception as described in Section 4.4 from the Day 1 Visit up to and including 100 days after the last dose of study medication
7. Must be willing and able to comply with all the requirements of the protocol for the entire duration of the study

Exclusion criteria 8

1. Must not Have received prior treatment with another anti-IGF-1R agent
2. Must not have a compressive optic neuropathy of TED that is expected to require surgical decompression in the immediate future.
3. Must not have corneal decompensation in the study eye unresponsive to medical management
4. Must not Have received systemic corticosteroids for any condition, including TED, or selenium within 2 weeks prior to the first dose of study medication (topical steroids including eye drops or multivitamins that contain selenium are permitted). Also exclusionary is periocular (including intraorbital) or intraocular administration of corticosteroids within 3 months prior to the first dose of study medication or having received greater than 3 periocular or intraocular corticosteroid injections at any time
5. Must not Have received other immunosuppressive agents, including rituximab, tocilizumab, secukimumab, satralizumab or anti-FcRn’s for any condition (including TED) within 8 weeks prior to the first dose of study medication or have received intraorbital administration of other such immunosuppressive agents at any time
6. Must not have received any other therapy for TED within 8 weeks prior to the first dose of study medication (artificial tears are permitted)
7. Must not have received an investigational agent for any condition (other than VRDN-001 or placebo associated with the VRDN-001-101 or VRDN-001- 301 pivotal studies) within 8 weeks prior to the first dose of study medication
8. Must not Have abnormal baseline audiometry Pure Tone Average (PTA) assessment or history of significant (as determined by the Investigator) ear pathology, relevant ear surgery or hearing loss

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall Responder Rate comprised of Proptosis Responder Rate in the most proptotic eye (i.e., reduction of proptosis of ≥ 2 mm from baseline [without a corresponding increase of ≥ 2 mm in the other eye]) at 3 weeks post the fifth IV infusion (i.e., Week 15) and Clinical Activity Responder Rate in the most proptotic eye (i.e., no worsening in CAS from baseline [without a corresponding increase of ≥2 points in the other eye]) at 3 weeks post the fifth IV infusion (i.e., Week 15)
2. Safety Endpoints: Adverse Events (AEs) and Serious Adverse Events (SAEs) will be monitored and recorded throughout the duration of the study. All clinically significant changes in other safety assessments will be recorded as AEs.

Secondary endpoints 3

1. Change from baseline in proptosis in the most proptotic eye at Week 15
2. Proptosis Responder Rate in the most proptotic eye as measured by exophthalmometer at Week 15.
3. Change from baseline in proptosis in the most proptotic eye as measured by exophthalmometer at Week 15.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Viridian Therapeutics Inc.

Sponsor organisation

Viridian Therapeutics Inc.

Address

221 Crescent Street Suite 103a

City

Waltham

Postcode

02453-3425

Country

United States

Scientific contact point

Organisation

Viridian Therapeutics S.à.r.l.

Contact name

Chief Development Officer

Public contact point

Organisation

Viridian Therapeutics S.à.r.l.

Contact name

Chief Development Officer

Third parties 11

Locations

8 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications