An Open Label, Randomized, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor, Administered Monthly as Monotherapy in Patients With Acromegaly
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 22
- 主要终点
- Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27
研究概览
简要总结
The purpose of this study was to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly.
详细描述
This was a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants were randomized to 1 of 2 treatment groups to receive IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants entered a 14-week post-treatment (PT) evaluation period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females with a documented diagnosis of Acromegaly* who are 18 to 75 years old (inclusive) at the time of informed consent.
- •Have had pituitary surgery (e.g. transsphenoidal) unless there was a contraindication to surgery and are either acromegaly medical treatment naïve, or who had not taken any other acromegaly medications prior to the screening visit as outlined below
- •bromocriptine: 2 weeks
- •cabergoline: 4 weeks
- •quinagolide: 4 weeks
- •octreotide daily injection (SC) or oral formulation: 4 weeks
- •pegvisomant: 4 weeks
- •octreotide LAR: 3 months
- •pasireotide LAR: 4 months
- •lanreotide (all formulations): 3 months
- •At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex.
- •Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, abstinent, or using 1 highly effective method of birth control
排除标准
- •Participants who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
- •Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial
- •Participants with a pituitary tumor that, per Investigator judgment, is worsening (e.g., either growing or at risk of compressing or abutting the optic chiasm or other vital structures) as assessed by pituitary/sellar MRI protocol at Screening or within 3 months of Screening. CT scan is allowed if MRI is contraindicated
- •Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (NYHA) Class 3 or 4
- •Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
- •Symptomatic cholelithiasis, and/or choledocholithiasis
研究组 & 干预措施
GHR-LRX 120 mg
Participants received GHR-LRX 120 mg subcutaneous (SC) injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
干预措施: GHR-LRX (Drug)
GHR-LRX 160 mg
Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
干预措施: GHR-LRX (Drug)
结局指标
主要结局
Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27
时间窗: Baseline to Week 27
IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Baseline of IGF-1 is defined as the average value of Screening and Day 1. A negative percent change from Baseline indicated improvement.
次要结局
- Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27)(At Week 27)
- Change From Baseline in Serum IGF-1 Over Time(Up to approximately 80 weeks)
- Percent Change From Baseline in Serum IGF-1 Over Time(Baseline, Week 3, 5, 7, 9, 11, 13, 15, 17, 21, 25, 27, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73)
- Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27)(At Week 27)