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

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Acromegaly

Treatments: Drug: GHR-LRX

Study type: Interventional

Funder types: Industry

Identifiers

NCT04522180

ISIS 766720-CS5

2020-000675-20 (EudraCT Number)

NCT04522180 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 34 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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34 participants in 2 patient groups

GHR-LRX 120 mg

Experimental group

Description:

Participants received GHR-LRX 120 mg subcutaneous (SC) injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).

Treatment:

Drug: GHR-LRX

GHR-LRX 160 mg

Experimental group

Description:

Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).

Treatment:

Drug: GHR-LRX