Clinical trial NCT03548415: Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acromegaly
Keywords: Acromegaly, IONIS-GHR-LRx
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-06-07
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change in Serum Insulin-like Growth Factor-1 (IGF-1) From Baseline to 28 Days After Last Dose
timeFrame: Baseline and 28 days after last dose (Day 141)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 211 days
measure: Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
timeFrame: Up to 211 days
measure: Number of Participants With TEAEs Related to Clinically Significant Physical Examination Findings
timeFrame: Up to 211 days
measure: Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
timeFrame: Up to 211 days
measure: Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Up to 211 days
Secondary outcomes:
measure: Number of Participants Achieving Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at 28 Days After Last Dose
timeFrame: Baseline to 28 days after last dose (Day 141)
measure: Number of Participants Achieving Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at 28 Days After Last Dose
timeFrame: Baseline to 28 days after last dose (Day 141)
measure: Change From Baseline in Serum IGF-1 Over Time
timeFrame: Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 141, 155, 183, and 211
measure: Percent Change From Baseline in Serum IGF-1 Over Time
timeFrame: Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB)
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Budapest
country: Hungary
facility: Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Szeged
country: Hungary
facility: Szeged University - Szent-Gyorgyi Albert Clinical Center - I. Belgyógyászati Klinika (Internal Medicine)
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos - Hospital of Oncology
city: Vilnius
country: Lithuania
facility: Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika
city: Chorzow
country: Poland
facility: B_Serwis Popenda Sp. J. Specjalistyczna Przychodnia Lekarsk
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach
city: Krakow
country: Poland
facility: Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o. o.
city: Nowa Sol
country: Poland
facility: Twoja Przychodnia - Centrum Medyczne Nowa Sol
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
city: Wroclaw
country: Poland
facility: Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.
city: Bucharest
country: Romania
facility: Centrul Medical Unirea - Bucuresti, Endocrinologie
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj - Napoca
city: Targu-Mures
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Timisoara
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Timisoara
city: Barnaul
country: Russian Federation
facility: Multi-field Medical Clinic Anturium LLC
city: Kazan
country: Russian Federation
facility: Interregional Clinical Diagnostic Center
city: Kemerovo
country: Russian Federation
facility: Kuzbass Clinical Hospital n.a. S.V. Belyaev
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "National Medical Research Center of Endocrinology" of the Ministry of Healthcare of the Russian Federation
city: Moscow
country: Russian Federation
facility: I.M. Sechenov Moscow First State Medical University
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Regional Clinical Hospital
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Hospital, Endocrinology Department
city: Rostov-On-Don
country: Russian Federation
facility: Rostov State Medical University
city: St. Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
city: Tver
country: Russian Federation
facility: State Budget Healthcare Institution of the Tver Region
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
Study officials:
References: