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Completed

NCT Number: NCT03548415

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

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

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Key information

Conditions

Acromegaly Bone Diseases Bone Diseases, Endocrine Brain Diseases Central Nervous System Diseases Endocrine System Diseases Hyperpituitarism Hypothalamic Diseases Musculoskeletal Diseases Nervous System Diseases Pituitary Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly, Budapest, Hungary

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Treatment and study plan

IONIS-GHR-LRx

Drug

IONIS GHR-LRx administered subcutaneously.

Placebo

Drug

Placebo administered subcutaneously.

Primary outcomes

  1. Percent Change in Serum Insulin-like Growth Factor-1 (IGF-1) From Baseline to 28 Days After Last Dose

    Time frame: Baseline and 28 days after last dose (Day 141)

    IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Percent change from Baseline in IGF-1 levels was measured at Day 141. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic (PD) activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

  2. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: Up to 211 days

    A TEAE was defined as an adverse event that occurred after the initiation of study drug dosing and before the end of the follow-up period.

  3. Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings

    Time frame: Up to 211 days

    Vitals signs included blood pressure, heart rate, respiratory rate, and temperature recorded throughout the study. Clinical significance was determined by the investigator.

  4. Number of Participants With TEAEs Related to Clinically Significant Physical Examination Findings

    Time frame: Up to 211 days

    Physical examination included weight and body mass index (BMI) recorded throughout the study. Clinical significance was determined by the investigator.

  5. Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings

    Time frame: Up to 211 days

    Clinical laboratory assessments included clinical chemistry, hematology, and urinalysis. Clinically-significant abnormal laboratory values were reported as TEAEs if the results may, in the opinion of the Investigator, constitute or be associated with an AE.

  6. Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings

    Time frame: Up to 211 days

    ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF.

Secondary outcomes

  1. Number of Participants Achieving Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at 28 Days After Last Dose

    Time frame: Baseline to 28 days after last dose (Day 141)

    Normalization of circulating IGF-1 is a validated marker for the treatment of acromegaly. IGF-1 assessments were based on a single serum sample taken in fasting conditions, prior to the study drug administration. Normal IGF-1 levels for a participant differ based on age and gender. Number of participants with a normal IGF-1 level which were 1.2 times within gender and age limits after 28 days of the last dose (Day 141) are presented. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

  2. Number of Participants Achieving Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at 28 Days After Last Dose

    Time frame: Baseline to 28 days after last dose (Day 141)

    Normalization of circulating IGF-1 is a validated marker for the treatment of acromegaly. IGF-1 assessments were based on a single serum sample taken in fasting conditions, prior to the study drug administration. Normal IGF-1 levels for a participant differ based on age and gender. Number of participants with a normal IGF-1 level which were 1.0 times within gender and age limits after 28 days of the last dose (Day 141) are presented. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

  3. Change From Baseline in Serum IGF-1 Over Time

    Time frame: Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 141, 155, 183, and 211

    IGF-1 is a hormone that manages the effects of GH in the body. Change from Baseline in IGF-1 levels was measured at multiple timepoints up to Day 211. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

  4. Percent Change From Baseline in Serum IGF-1 Over Time

    Time frame: Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211

    IGF-1 is a hormone that manages the effects of GH in the body. Percent change from Baseline in IGF-1 levels was measured at multiple timepoints up to Day 211. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

Sponsors and collaborators

Lead sponsor

Ionis Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Double-Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of ISIS 766720 (IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor) Administered Once Every 28 Days for 16 Weeks in Patients With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands (SRL)

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Jun 7, 2018
Registry last updated
Nov 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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