Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in up to 42 Adult Patients With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands

This short-term study will assess changes in serum insulin-like growth factor 1 (IGF-1) over
a 16-week treatment period in a patient population diagnosed with Acromegaly being treated
with Long-acting Somatostatin Receptor Ligands (SRL)

Inclusion Criteria:

1. Males or females with documented diagnosis of Acromegaly, aged 18-75 years old
(inclusive) at the time of informed consent

2. Patients 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.

3. At Screening, serum IGF-1 (performed at central lab) between 1.3 to 5 x 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. Patients who received surgery for pituitary adenoma within the last 6 months before
the trial, or planning to receive surgery during the trial

2. Patients who received radiotherapy for pituitary adenoma within the last 3 years
before the trial, and/or planning to receive radiotherapy during the trial

3. Patients with pituitary tumor that, per Investigator judgement, is worsening as
assessed by pituitary/sellar MRI protocol at Screen or within 6 months of screening

4. Evidence of decompensated cardiac function per medical judgement and/or NYHA class 3
or 4

5. Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment

6. Patients may not have insulin, chronic systemic use of glucocorticoids, weight loss
medications or participate in weight loss programs within 2 months before
randomization and during study participation.

7. Patients 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