A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of ISIS 766720 (IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor) Administered Once Every 28 Days for 16 Weeks in Patients With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands (SRL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 32
- 主要终点
- Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings
研究概览
简要总结
The purpose of this study was to assess the safety, tolerability, and efficacy of IONIS-GHR-LRx in up to 60 participants with acromegaly.
详细描述
This short-term study assessed changes in serum insulin-like growth factor 1 (IGF-1) over a 16-week treatment period in a participant population diagnosed with acromegaly being treated with long-acting somatostatin receptor ligands (SRL).
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
- Double (Participant, Investigator)
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 documented diagnosis of acromegaly, aged 18-75 years old (inclusive) at the time of informed consent
- •Participants must be on stable maximum or maximally tolerated dose of SRL (Lanreotide Autogel or Octreotide LAR, per treating physician judgment) every 28 days for a minimum of 3 months prior to screening and will be required to continue their stable dose of SRL throughout the study. Prior use of other medications for treating acromegaly is allowed but not within 6 weeks of screening.
- •At Screening, serum insulin-like growth factor 1 (IGF-1) (performed at central lab) between 1.3 to 5 x upper limit of normal (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 6 months before the trial, or planning to receive surgery during the trial
- •Participants who received radiotherapy for pituitary adenoma within the last 3 years before the trial, and/or planning to receive radiotherapy during the trial
- •Participants with pituitary tumor that, per Investigator judgement, is worsening as assessed by pituitary/sellar magnetic resonance imaging (MRI) protocol at Screen or within 6 months of screening
- •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
- •Participants may not have chronic systemic use of glucocorticoids, weight loss medications or participate in weight loss programs within 2 months before randomization and during study participation.
- •Participants on anti-diabetes medication or estrogen containing medications must be on a stable dose and regimen for >= 3 months prior to screening and throughout the trial
- •Participants taking glucagon-like peptide 1 (GLP-1) agonists or insulin can be allowed with prior consultation with the Sponsor Medical Monitor
研究组 & 干预措施
Placebo
Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.
干预措施: Placebo (Drug)
Cohort A: IONIS GHR-LRx, 60 mg
Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.
干预措施: IONIS-GHR-LRx (Drug)
Cohort B: IONIS GHR-LRx, 80 mg
Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.
干预措施: IONIS-GHR-LRx (Drug)
Cohort C: IONIS GHR-LRx, 120 mg
Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.
干预措施: IONIS-GHR-LRx (Drug)
Cohort D: IONIS GHR-LRx, 160 mg
Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
干预措施: IONIS-GHR-LRx (Drug)
结局指标
主要结局
Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings
时间窗: Up to 211 days
ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF.
Percent Change in Serum Insulin-like Growth Factor-1 (IGF-1) From Baseline to 28 Days After Last Dose
时间窗: Baseline and 28 days after last dose (Day 141)
IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Percent change from Baseline in IGF-1 levels was measured at Day 141. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic (PD) activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.
Number of Participants With TEAEs Related to Clinically Significant Physical Examination Findings
时间窗: Up to 211 days
Physical examination included weight and body mass index (BMI) recorded throughout the study. Clinical significance was determined by the investigator.
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
时间窗: Up to 211 days
Clinical laboratory assessments included clinical chemistry, hematology, and urinalysis. Clinically-significant abnormal laboratory values were reported as TEAEs if the results may, in the opinion of the Investigator, constitute or be associated with an AE.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 211 days
A TEAE was defined as an adverse event that occurred after the initiation of study drug dosing and before the end of the follow-up period.
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
时间窗: Up to 211 days
Vitals signs included blood pressure, heart rate, respiratory rate, and temperature recorded throughout the study. Clinical significance was determined by the investigator.
次要结局
- Change From Baseline in Serum IGF-1 Over Time(Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 141, 155, 183, and 211)
- Number of Participants Achieving Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at 28 Days After Last Dose(Baseline to 28 days after last dose (Day 141))
- Percent Change From Baseline in Serum IGF-1 Over Time(Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211)
- Number of Participants Achieving Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at 28 Days After Last Dose(Baseline to 28 days after last dose (Day 141))