A Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx Administered in Patients With Acromegaly

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly.

Detailed Description
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This is a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants will be randomized to 1 of 3 treatment groups to receive a single dose of IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants will enter a 14-week post-treatment (PT) evaluation period.

Official Title
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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

Conditions
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Acromegaly

Intervention / Treatment
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* Drug: IONIS-GHR-LRx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IONIS-GHR-LRx Dose 1<br>Single dose of IONIS-GHR-LRx Dose 1 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). | Drug: IONIS-GHR-LRx<br>* IONIS-GHR-LRx will be administered by SC injection.<br>|
| Experimental: IONIS-GHR-LRx Dose 2<br>Single dose of IONIS-GHR-LRx Dose 2 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). | Drug: IONIS-GHR-LRx<br>* IONIS-GHR-LRx will be administered by SC injection.<br>|
| Experimental: IONIS-GHR-LRx Dose 3<br>Single dose of IONIS-GHR-LRx Dose 3 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). | Drug: IONIS-GHR-LRx<br>* IONIS-GHR-LRx will be administered by SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Insulin-like Growth Factor I (IGF-1) to Week 27 |  | Up to Week 27 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at Day 183 (Week 27) |  | At Week 27 | 
| Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.0 Times of 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 |  | Up to approximately 80 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acromegaly, IONIS-GHR-LRx