2024-512244-36-00已完成3 期
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 (NHVs) and subjects with thyroid eye disease (TED)
Viridian Therapeutics Inc.14 个研究点 分布在 4 个国家目标入组 48 人开始时间: 2024年10月4日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 14
- 主要终点
- - 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 measurements will be recorded as AEs.
研究概览
简要总结
To establish the safety, tolerability, and efficacy of VRDN-001, and the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of VRDN-001 in NHV and TED patients over a dose range of 3.0 to 20.0 mg/kg.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Enrollment in the HV and Active TED MAD cohorts has been completed. The inclusion criteria corresponding to the HV and Active and Chronic TED MAD cohorts are now described in Appendices 4 and 5, respectively.
- •If female, have a negative serum pregnancy test at screening and further negative urine tests immediately before each dose of study medication following the last dose of study medication as described in Appendix 1C if the participant is a woman of childbearing potential (including those with <2 years since the onset of menopause, amenorrhea for <2 year, or not surgically sterile); such participants must 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 Screening up to and including 100 days after the last dose of study medication. If the participant is initiating hormonal contraception at time of Screening or 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
- •Be surgically sterile males for at least 6 weeks, or 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 Screening up to and including 100 days after the last dose of study medication
- •Be willing and able to comply with all the requirements of the protocol for the entire duration of the study.
- •Active TED Pivotal (THRIVE) participants Participants must:
- •Be able to understand the study procedures and the risks involved and be willing to provide written informed consent before the first study- related activity
- •Be an adult male or female participant, at least 18 years of age or older
- •Have had a clinical diagnosis of TED with a CAS of ≥ 3 on the 7-item scale for the study eye
- •Have moderate to severe (i.e., has an appreciable impact on daily living) active TED associated with proptosis of ≥3 mm above normal values for race and gender in the opinion of the investigator and at least one of the following: lid retraction of ≥2 mm, moderate or severe soft tissue involvement, inconstant or constant diplopia, spontaneous retrobulbar pain or pain on eye movement, swelling of the conjunctiva, eyelids or plica, or redness of the eyelids or plica in the study eye
- •Have documented evidence of ocular symptoms or signs associated with active TED that began within 15 months prior to study screening
- •VRDN-001 can be started concomitantly with attempts to achieve euthyroid status. Underlying thyroid status is not an inclusion criterion.
- •Not require expected immediate surgical ophthalmological or orbital surgery in the study eye for any reason
- •VRDN-001 can be used with caution in patients with diabetes mellitus. Diabetic participants should be monitored by their endocrinologist or other appropriately trained personnel and have at study entry a glycated hemoglobin (HbA1c) of <8.5%
排除标准
- •Exclusion Criteria Enrollment in the HV and Active TED MAD cohorts has been completed. The exclusion criteria corresponding to the HV and Active and Chronic TED MAD cohorts are now described in Appendices 4 and 5, respectively.
- •Have a compressive optic neuropathy of TED that is expected to require surgical decompression in the immediate future.
- •Have corneal decompensation in the study eye unresponsive to medical management
- •Have a decrease in CAS of ≥2 points in the study eye between screening assessment and Day -1
- •Have a decrease in proptosis of ≥2 mm in the study eye between screening assessment and Day -1
- •Have had previous orbital irradiation or decompression surgery involving excision of fat for TED to the study eye's orbit
- •Have history of or screening audiometry assessment of significant (as determined by the Investigator) ear pathology, relevant ear surgery or hearing loss
- •Have inflammatory bowel disease (e.g., biopsy proven or clinical evidence of inflammatory bowel disease)
- •Have a known hypersensitivity to any of the components of VRDN- 001 or placebo formulations, or prior hypersensitivity to monoclonal antibodies (mAbs)
- •Have any condition, which in the opinion of the Investigator, would preclude inclusion in the study
- •Have a positive test for human immunodeficiency virus (HIV-1 and HIV-2)
- •Active TED Pivotal (THRIVE) participants Participants must not: Have used systemic corticosteroids for any condition, including TED, or selenium within 2 weeks prior to the first dose of study medication (topical steroids or multivitamins that contain selenium are permitted)
- •Have a positive test for active hepatitis B or hepatitis C infection
- •Have previously participated in this study or any study of VRDN-001
- •French participating sites only: In accordance with the provisions of articles L.1121-5 et seq. of the Public Health Code, pregnant or breast- feeding women, persons deprived of their liberty by a judicial or administrative decision, persons under psychiatric care without their consent, minors and adults under a legal protection measure must not be included
- •Note: Prior thyroidectomy, radioactive iodine (RAI) treatment, or orbital decompression surgery limited to bone only are NOT exclusions.
- •Have received other immunosuppressive agents, including rituximab, or tocilizumab, for any condition, including TED, within 8 weeks prior to the first dose of study medication
- •Have received any other therapy for TED within 8 weeks prior to the first dose of study medication (artificial tears are permitted)
- •Have received an investigational agent for any condition within 8 weeks prior to the first dose of study medication
- •Have a pre-existing ophthalmic condition in the study eye which in the opinion of the Investigator, would confound interpretation of the study results
- •Be a pregnant or lactating woman
- •Be an active alcoholic or illicit drug user or considered at high risk of relapse by the Investigator
- •Active TED Pivotal (THRIVE) participants Participants must not:
- •Have received prior treatment with another anti-IGF-1R therapy or any investigational agent for TED
结局指标
主要结局
- 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 measurements will be recorded as AEs.
- 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 measurements will be recorded as AEs.
- PRIMARY EFFICACY ENDPOINT IN THE USA, CANADA AND CHINA IN THE PIVOTAL PORTION OF THE STUDY (THRIVE) Proptosis Responder Rate in the study eye (i.e., reduction of proptosis of ≥ 2 mm from baseline [without a corresponding increase of ≥ 2 mm in the fellow eye] as measured by exophthalmometer) at 3 weeks post the fifth infusion (i.e., Week 15)
- PRIMARY EFFICACY ENDPOINT IN THE USA, CANADA AND CHINA IN THE PIVOTAL PORTION OF THE STUDY (THRIVE) Proptosis Responder Rate in the study eye (i.e., reduction of proptosis of ≥ 2 mm from baseline [without a corresponding increase of ≥ 2 mm in the fellow eye] as measured by exophthalmometer) at 3 weeks post the fifth infusion (i.e., Week 15)
- AUS, EU AND UK: Overall Responder Rate comprised of Proptosis Responder Rate in the study eye (i.e., reduction of proptosis of ≥ 2 mm from baseline [without a corresponding increase of ≥ 2 mm in the fellow eye] as measured by exophthalmometer) at 3 weeks post the fifth infusion (i.e., Week 15) and Clinical Activity Responder Rate in the study eye (i.e., reduction in CAS ≥ 2 points from baseline [without a corresponding increase of ≥ 2 points in the fellow eye]) at 3 weeks post the 5 infusion
- AUS, EU AND UK: Overall Responder Rate comprised of Proptosis Responder Rate in the study eye (i.e., reduction of proptosis of ≥ 2 mm from baseline [without a corresponding increase of ≥ 2 mm in the fellow eye] as measured by exophthalmometer) at 3 weeks post the fifth infusion (i.e., Week 15) and Clinical Activity Responder Rate in the study eye (i.e., reduction in CAS ≥ 2 points from baseline [without a corresponding increase of ≥ 2 points in the fellow eye]) at 3 weeks post the 5 infusion
次要结局
- Key Secondary Endpoints in Australia, EU and UK in the Pivotal portion of the Study (THRIVE): • Change from Baseline in proptosis in the study eye as measured by exophthalmometer at Week 15
- Change from baseline in CAS in the study eye at Week 15
- Diplopia Resolution Rate at (i.e., reduction in Gorman Subjective Diplopia Score to 0 from baseline for participants with baseline Gorman Subjective Diplopia Score >0) Week 15
- Proportion of participants with a CAS score of zero or one in the study eye at Week 15
- Exploratory Endpoints in Australia, Canada, China, EU, UK and US in the Pivotal portion of the Study (THRIVE): • Proptosis Responder Rate in the study eye as measured by exophthalmometer) at Week 24 (12 weeks post fifth infusion), Week 36 (24 weeks post fifth infusion) and Week 52
- Proptosis Responder Rate in the fellow eye (i.e., reduction of proptosis of ≥ 2 mm from baseline as measured by exophthalmometer) at Weeks 15, 24, 36 and 52
- Durability of Proptosis Response in the study eye at Weeks 24, 36 and 52
- Time to First Proptosis Response in the study eye
- Clinical Activity Responder Rate in the study eye at Weeks 24, 36 and 52
- Clinical Activity Responder Rate in the fellow eye at Weeks 15, 24, 36 and 52
- Change from baseline in CAS in the study eye at Weeks 24, 36 and 52
- Change from baseline in CAS in the fellow eye at Weeks 15, 24, 36 and 52
- Time to first CAS Response in the study eye
- Overall Responder Rate in the study eye at Weeks 24, 36 and 52
- Overall Responder Rate in the fellow eye at Weeks 15, 24, 36 and 52
- Time to First Overall Response in the study eye
- Diplopia Resolution Rate at Weeks 24, 36 and 52
- Proportion of participants with a CAS score of zero or one in the study eye at Weeks 24, 36 and 52
- Proportion of participants with a CAS score of zero or one in the fellow eye at Weeks 15, 24, 36 and 52
- Proptosis Response Rate in the study eye as measured by magnetic resonance imaging [MRI] or Computed Tomography [CT – where allowed by local health authorities] at Weeks 15, 24, 36 and 52
- Change from Baseline in the following parameters at Weeks 15, 24, 36 and 52: - Proptosis in the study eye by MRI (or CT – where allowed by local health authorities)
- - Extraocular muscles in the study eye as determined by MRI (or CT – where allowed by local health authorities)
- - Orbital fat in the study eye as measured by MRI (or CT – where allowed by local health authorities)
- - Manual measurement of lid retraction in the study eye
- - Graves' Orbitopathy-Quality of Life (GO-QoL) combined score
- - GO-QoL activity subscale
- - GO-QoL appearance subscale - EQ-5D-5L QoL questionnaire
- - Visual Acuity (VA); - Gorman Subjective Displopia Score
- • VRDN-001, IGF-1 and ADA at various time points pre- and post- infusions as described in Appendix 1C.
研究者
Chief Medical Officer
Scientific
Viridian Therapeutics S.à.r.l.
研究点 (14)
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