AzTrials
AzTrials

AcromegalyPhase 2NCT03548415

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

A Phase 2 study testing IONIS-GHR-LRx in people with Acromegaly, run by Ionis Pharmaceuticals, Inc. at 33 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Acromegaly
What is being tested?
IONIS-GHR-LRx
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
43 participants
Where
33 sitesin 7 countries
Study dates
13 Sep 2018to 2 Apr 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

33 sites in 7 countries.

33 sites in 7 countries

Russia10 sites

  • Multi-field Medical Clinic Anturium LLC

    Barnaul, 656043

  • Interregional Clinical Diagnostic Center

    Kazan', 420101

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

    Kemerovo, 650066

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

    Moscow, 117036

  • I.M. Sechenov Moscow First State Medical University

    Moscow, 119992

  • Novosibirsk State Regional Clinical Hospital

    Novosibirsk, 630087

  • Orenburg Regional Clinical Hospital, Endocrinology Department

    Orenburg, 460018

  • Rostov State Medical University

    Rostov-on-Don, 344022

  • Almazov National Medical Research Centre

    Saint Petersburg, 194156

  • State Budget Healthcare Institution of the Tver Region

    Tver', 170036

Other trials in Russia

United States7 sites

  • University of Alabama at Birmingham (UAB)

    Birmingham, Alabama, 35294

  • Northwestern University

    Chicago, Illinois, 60611

  • Palm Research Center, Inc.

    Las Vegas, Nevada, 89128

  • Palm Research Center, Inc.

    Las Vegas, Nevada, 89148

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Oregon Health & Science University (OHSU)

    Portland, Oregon, 97239

Other trials in United States

Poland6 sites

  • B_Serwis Popenda Sp. J. Specjalistyczna Przychodnia Lekarsk

    Chorzów, 41-500

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

    Katowice, 40-952

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

    Krakow, 31-011

  • Twoja Przychodnia - Centrum Medyczne Nowa Sol

    Nowa Sól, 67-00

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

    Warsaw, 03-242

  • Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.

    Wroclaw, 51-162

Other trials in Poland

Romania4 sites

  • Centrul Medical Unirea - Bucuresti, Endocrinologie

    Bucharest, 010567

  • Spitalul Clinic Judetean de Urgenta Cluj - Napoca

    Cluj-Napoca, 400349

  • Spitalul Clinic Judetean Mures

    Târgu Mureş, 540142

  • Spitalul Clinic Judetean de Urgenta Timisoara

    Timișoara, 300723

Other trials in Romania

Hungary3 sites

  • Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly

    Budapest, 1062

  • Debreceni Egyetem Klinikai Kozpont

    Debrecen, 4032

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

    Szeged, 6720

Other trials in Hungary

Lithuania2 sites

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

    Kaunas, 50009

  • Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika

    Vilnius, 08661

Other trials in Lithuania

Serbia1 site

  • Clinical Center of Serbia

    Belgrade, 11000

Other trials in Serbia

About this study

Official 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)

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

Read the detailed 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).

Conditions
Acromegaly
Being tested
IONIS-GHR-LRx, Placebo
Keywords
Acromegaly, IONIS-GHR-LRx
Medical subject headings
Acromegaly

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IONIS-GHR-LRxDrug

    IONIS GHR-LRx administered subcutaneously.

  • PlaceboDrug

    Placebo administered subcutaneously.

Study groups in NCT03548415
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.
Receives: Drug: Placebo
Cohort A: IONIS GHR-LRx, 60 mgExperimentalParticipants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.
Receives: Drug: IONIS-GHR-LRx
Cohort B: IONIS GHR-LRx, 80 mgExperimentalParticipants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.
Receives: Drug: IONIS-GHR-LRx
Cohort C: IONIS GHR-LRx, 120 mgExperimentalParticipants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.
Receives: Drug: IONIS-GHR-LRx
Cohort D: IONIS GHR-LRx, 160 mgExperimentalParticipants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Receives: Drug: IONIS-GHR-LRx

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Up to 211 days

  3. 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.

    Measured: Up to 211 days

  4. 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.

    Measured: Up to 211 days

  5. 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.

    Measured: Up to 211 days

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

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

    Measured: Up to 211 days

Secondary outcomes (4)

  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

    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.

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

  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

    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.

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

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

    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.

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

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

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2018
  2. Study start13 Sep 2018
  3. Primary completion18 Feb 2021
  4. Study completion2 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03548415
Sponsor's protocol ID
ISIS 766720-CS2
Other IDs
2017-004259-22, 2017
Status last verified
Oct 2022
First submitted
22 May 2018
Last updated
14 Nov 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IONIS-GHR-LRx in people with Acromegaly, run by Ionis Pharmaceuticals, Inc. at 33 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in Russia, United States, Poland, Romania, Hungary and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03548415.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2022; AzTrials last refreshed its copy on 8 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in