Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Acromegaly

Treatments: Drug: IONIS-GHR-LRx; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03548415

2017-004259-22 (EudraCT Number)

ISIS 766720-CS2

Details and patient eligibility

About

The purpose of this study was to assess the safety, tolerability, and efficacy of IONIS-GHR-LRx in up to 60 participants with acromegaly.

Full description

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).

Enrollment: 43 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or females with documented diagnosis of acromegaly, aged 18-75 years old (inclusive) at the time of informed consent
2. 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.
3. 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
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 6 months before the trial, or planning to receive surgery during the trial
2. Participants who received radiotherapy for pituitary adenoma within the last 3 years before the trial, and/or planning to receive radiotherapy during the trial
3. 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
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. 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.
7. 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
8. Participants taking glucagon-like peptide 1 (GLP-1) agonists or insulin can be allowed with prior consultation with the Sponsor Medical Monitor

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

43 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.

Treatment:

Drug: Placebo

Cohort A: IONIS GHR-LRx, 60 mg

Experimental group

Description:

Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.

Treatment:

Drug: IONIS-GHR-LRx

Cohort B: IONIS GHR-LRx, 80 mg

Experimental group

Description:

Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.

Treatment:

Drug: IONIS-GHR-LRx

Cohort C: IONIS GHR-LRx, 120 mg

Experimental group

Description:

Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.

Treatment:

Drug: IONIS-GHR-LRx

Cohort D: IONIS GHR-LRx, 160 mg

Experimental group

Description:

Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.

Treatment:

Drug: IONIS-GHR-LRx