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

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

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.

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.

Inclusion Criteria:

1. Males or females with a documented diagnosis of Acromegaly* who are 18 to 75 years old (inclusive) at the time of informed consent.

2. 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

3. At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex.

4. 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:

1. Participants who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
2. Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial
3. 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
4. Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (NYHA) Class 3 or 4
5. Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
6. Symptomatic cholelithiasis, and/or choledocholithiasis