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

NCT03548415 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ISIS 766720-CS22017-004259-22
• Study Type: interventional
• Target: 43
• Locations: 7 countries
• Sites: 33

Brief Summary

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

Conditions

Acromegaly

Keywords

Acromegaly, IONIS-GHR-LRx

Outcome Measures

Primary Outcomes (6)

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

  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.

  Baseline and 28 days after last dose (Day 141)

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

  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.

  Up to 211 days

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

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

  Up to 211 days

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

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

  Up to 211 days

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

  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.

  Up to 211 days

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

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

  Up to 211 days

Secondary Outcomes (4)

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

  Baseline to 28 days after last dose (Day 141)

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

  Baseline to 28 days after last dose (Day 141)

• Change From Baseline in Serum IGF-1 Over Time

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

• Percent Change From Baseline in Serum IGF-1 Over Time

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

Study Arms (5)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Cohort A: IONIS GHR-LRx, 60 mg

EXPERIMENTAL

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

Drug: IONIS-GHR-LRx

Cohort B: IONIS GHR-LRx, 80 mg

EXPERIMENTAL

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

Drug: IONIS-GHR-LRx

Cohort C: IONIS GHR-LRx, 120 mg

EXPERIMENTAL

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

Drug: IONIS-GHR-LRx

Cohort D: IONIS GHR-LRx, 160 mg

EXPERIMENTAL

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

Drug: IONIS-GHR-LRx

Interventions

IONIS-GHR-LRx DRUG

IONIS GHR-LRx administered subcutaneously.

Cohort A: IONIS GHR-LRx, 60 mg; Cohort B: IONIS GHR-LRx, 80 mg; Cohort C: IONIS GHR-LRx, 120 mg; Cohort D: IONIS GHR-LRx, 160 mg

Placebo DRUG

Placebo administered subcutaneously.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (33)

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35294, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Palm Research Center, Inc.

Las Vegas, Nevada, 89128, United States

Location

Palm Research Center, Inc.

Las Vegas, Nevada, 89148, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly

Budapest, 1062, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Szeged University - Szent-Gyorgyi Albert Clinical Center - I. Belgyógyászati Klinika (Internal Medicine)

Szeged, 6720, Hungary

Location

Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos - Hospital of Oncology

Kaunas, 50009, Lithuania

Location

Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika

Vilnius, 08661, Lithuania

Location

B_Serwis Popenda Sp. J. Specjalistyczna Przychodnia Lekarsk

Chorzów, 41-500, Poland

Location

Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, 40-952, Poland

Location

Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o. o.

Krakow, 31-011, Poland

Location

Twoja Przychodnia - Centrum Medyczne Nowa Sol

Nowa Sól, 67-00, Poland

Location

Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii

Warsaw, 03-242, Poland

Location

Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.

Wroclaw, 51-162, Poland

Location

Centrul Medical Unirea - Bucuresti, Endocrinologie

Bucharest, 010567, Romania

Location

Spitalul Clinic Judetean de Urgenta Cluj - Napoca

Cluj-Napoca, 400349, Romania

Location

Spitalul Clinic Judetean Mures

Târgu Mureş, 540142, Romania

Location

Spitalul Clinic Judetean de Urgenta Timisoara

Timișoara, 300723, Romania

Location

Multi-field Medical Clinic Anturium LLC

Barnaul, 656043, Russia

Location

Interregional Clinical Diagnostic Center

Kazan', 420101, Russia

Location

Kuzbass Clinical Hospital n.a. S.V. Belyaev

Kemerovo, 650066, Russia

Location

Federal State Budget Institution "National Medical Research Center of Endocrinology" of the Ministry of Healthcare of the Russian Federation

Moscow, 117036, Russia

Location

I.M. Sechenov Moscow First State Medical University

Moscow, 119992, Russia

Location

Novosibirsk State Regional Clinical Hospital

Novosibirsk, 630087, Russia

Location

Orenburg Regional Clinical Hospital, Endocrinology Department

Orenburg, 460018, Russia

Location

Rostov State Medical University

Rostov-on-Don, 344022, Russia

Location

Almazov National Medical Research Centre

Saint Petersburg, 194156, Russia

Location

State Budget Healthcare Institution of the Tver Region

Tver', 170036, Russia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

MeSH Terms

Conditions

Acromegaly

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

While no longer powered to assess the primary endpoint (% IGF- lowering at Day 141) in accordance with the protocol, the study did permit placebo-controlled evaluation of safety and efficacy.

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc
• Organization: Ionis Pharmaceuticals, Inc

patients@ionisph.com

800-679-4747

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: June 7, 2018
• Study Start: September 13, 2018
• Primary Completion: February 18, 2021
• Study Completion: April 2, 2021
• Last Updated: November 14, 2022
• Results First Posted: November 14, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

LI (2); RO (4); RU (10); HU (3); US (7); PL (6); SE (1)