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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004259-22 | EudraCT Number |
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The purpose of this study was to assess the safety, tolerability, and efficacy of IONIS-GHR-LRx in up to 60 participants with acromegaly.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks. |
|
| Cohort A: IONIS GHR-LRx, 60 mg | Experimental | Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks. |
|
| Cohort B: IONIS GHR-LRx, 80 mg | Experimental | Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks. |
|
| Cohort C: IONIS GHR-LRx, 120 mg | Experimental | Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks. |
|
| Cohort D: IONIS GHR-LRx, 160 mg | Experimental | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IONIS-GHR-LRx | Drug | IONIS GHR-LRx administered subcutaneously. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham (UAB) | Birmingham | Alabama | 35294 | United States | ||
| St. Joseph's Hospital and Medical Center |
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Adult participants diagnosed with acromegaly were randomized into 4 cohorts [Cohorts A and B in 2:1 ratio; Cohorts C and D in 5:1 ratio] to receive IONIS GHR-LRx or placebo. Due to enrollment difficulties associated with (COVID-19) pandemic, treatment groups IONIS GHR-LRx, 120 mg and IONIS GHR-LRx, 160 mg did not complete enrollment resulting in cohort sizes smaller than planned.
Participants took part in the study at 24 investigative sites in Lithuania, Hungary, the United States of America, Serbia, Russia, Poland, and Romania from 13 September 2018 to 02 April 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks. |
| FG001 | Cohort A: IONIS GHR-LRx, 60 mg | Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 18, 2020 |
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| Placebo | Drug | Placebo administered subcutaneously. |
|
| 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 |
| 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 | 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. | Baseline to 28 days after last dose (Day 141) |
| 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. | 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 | 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. | Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211 |
| Phoenix |
| Arizona |
| 85013 |
| United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Palm Research Center, Inc. | Las Vegas | Nevada | 89128 | United States |
| Palm Research Center, Inc. | Las Vegas | Nevada | 89148 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Oregon Health & Science University (OHSU) | Portland | Oregon | 97239 | United States |
| Magyar Honvedseg Allami Egeszsegugyi Kozpont, II. sz Belgyogyaszat Osztaly | Budapest | 1062 | Hungary |
| Debreceni Egyetem Klinikai Kozpont | Debrecen | 4032 | Hungary |
| Szeged University - Szent-Gyorgyi Albert Clinical Center - I. Belgyógyászati Klinika (Internal Medicine) | Szeged | 6720 | Hungary |
| Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos - Hospital of Oncology | Kaunas | 50009 | Lithuania |
| Vaidoto Urbanaviciaus Individuali imone - Endokrinologijos klinika | Vilnius | 08661 | Lithuania |
| B_Serwis Popenda Sp. J. Specjalistyczna Przychodnia Lekarsk | Chorzów | 41-500 | Poland |
| Uniwersyteckie Centrum Kliniczne im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach | Katowice | 40-952 | Poland |
| Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o. o. | Krakow | 31-011 | Poland |
| Twoja Przychodnia - Centrum Medyczne Nowa Sol | Nowa Sól | 67-00 | Poland |
| Mazowiecki Szpital Brodnowski - Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii | Warsaw | 03-242 | Poland |
| Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p. | Wroclaw | 51-162 | Poland |
| Centrul Medical Unirea - Bucuresti, Endocrinologie | Bucharest | 010567 | Romania |
| Spitalul Clinic Judetean de Urgenta Cluj - Napoca | Cluj-Napoca | 400349 | Romania |
| Spitalul Clinic Judetean Mures | Târgu Mureş | 540142 | Romania |
| Spitalul Clinic Judetean de Urgenta Timisoara | Timișoara | 300723 | Romania |
| Multi-field Medical Clinic Anturium LLC | Barnaul | 656043 | Russia |
| Interregional Clinical Diagnostic Center | Kazan' | 420101 | Russia |
| Kuzbass Clinical Hospital n.a. S.V. Belyaev | Kemerovo | 650066 | Russia |
| Federal State Budget Institution "National Medical Research Center of Endocrinology" of the Ministry of Healthcare of the Russian Federation | Moscow | 117036 | Russia |
| I.M. Sechenov Moscow First State Medical University | Moscow | 119992 | Russia |
| Novosibirsk State Regional Clinical Hospital | Novosibirsk | 630087 | Russia |
| Orenburg Regional Clinical Hospital, Endocrinology Department | Orenburg | 460018 | Russia |
| Rostov State Medical University | Rostov-on-Don | 344022 | Russia |
| Almazov National Medical Research Centre | Saint Petersburg | 194156 | Russia |
| State Budget Healthcare Institution of the Tver Region | Tver' | 170036 | Russia |
| Clinical Center of Serbia | Belgrade | 11000 | Serbia |
| FG002 | Cohort B: IONIS GHR-LRx, 80 mg | Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks. |
| FG003 | Cohort C: IONIS GHR-LRx, 120 mg | Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks. |
| FG004 | Cohort D: IONIS GHR-LRx, 160 mg | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
| Per-Protocol Set | The Per-Protocol Set included all randomized participants who received at least 5 of the 6 doses of Study Drug and had at least one post-baseline efficacy or pharmacodynamic assessment, with the first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks. |
| BG001 | Cohort A: IONIS GHR-LRx, 60 mg | Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks. |
| BG002 | Cohort B: IONIS GHR-LRx, 80 mg | Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks. |
| BG003 | Cohort C: IONIS GHR-LRx, 120 mg | Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks. |
| BG004 | Cohort D: IONIS GHR-LRx, 160 mg | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Per-protocol Set included all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or pharmacodynamic assessment, received at least 5 of the 6 doses of Study Drug with the first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Low dose refers to 60 mg or 80 mg, High dose refers to 120 mg or 160 mg. | Posted | Mean | Standard Deviation | percent change | Baseline and 28 days after last dose (Day 141) |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | 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. | The Safety Set included all participants who were randomized and received at least one dose of Study Drug. | Posted | Count of Participants | Participants | Up to 211 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | 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. | The Safety Set included all participants who were randomized and received at least one dose of Study Drug. | Posted | Count of Participants | Participants | Up to 211 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | 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. | The Safety Set included all participants who were randomized and received at least one dose of Study Drug. | Posted | Count of Participants | Participants | Up to 211 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | 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. | The Safety Set included all participants who were randomized and received at least one dose of Study Drug. | Posted | Count of Participants | Participants | Up to 211 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings | ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF. | The Safety Set included all participants who were randomized and received at least one dose of Study Drug. | Posted | Count of Participants | Participants | Up to 211 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The Per-protocol Set included all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or pharmacodynamic assessment, received at least 5 of the 6 doses of Study Drug with the first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Low dose refers to 60 mg or 80 mg, High dose refers to 120 mg or 160 mg. | Posted | Count of Participants | Participants | Baseline to 28 days after last dose (Day 141) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The Per-protocol Set included all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or pharmacodynamic assessment, received at least 5 of the 6 doses of Study Drug with the first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Low dose refers to 60 mg or 80 mg, High dose refers to 120 mg or 160 mg. | Posted | Count of Participants | Participants | Baseline to 28 days after last dose (Day 141) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per-protocol Set:all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or PD assessment, received at least 5 of 6 doses of Study Drug with first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Number analyzed is the number of participants with data available at specific timepoints. Low dose refers to 60 mg or 80 mg,High dose refers to 120 mg or 160 mg. | Posted | Mean | Standard Deviation | nanograms per milliliter | Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 141, 155, 183, and 211 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Per-protocol Set:all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or PD assessment, received at least 5 of 6 doses of Study Drug with first 3 doses administered on schedule,and had no significant protocol deviations that would have been expected to affect efficacy. Number analyzed is number of participants with data available for analysis at specific timepoint.Low dose refers to 60 mg or 80 mg,High dose refers to 120mg or 160mg. | Posted | Mean | Standard Deviation | percent change | Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211 |
|
Up to 211 days
The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks. | 0 | 12 | 0 | 12 | 8 | 12 |
| EG001 | Cohort A: IONIS GHR-LRx, 60 mg | Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks. | 1 | 12 | 1 | 12 | 11 | 12 |
| EG002 | Cohort B: IONIS GHR-LRx, 80 mg | Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks. | 0 | 11 | 1 | 11 | 7 | 11 |
| EG003 | Cohort C: IONIS GHR-LRx, 120 mg | Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG004 | Cohort D: IONIS GHR-LRx, 160 mg | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. | 0 | 6 | 1 | 6 | 5 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intra-abdominal haemorrhage | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Gastrointestinal bacterial infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cholecystitis | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Cervicitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Enterovirus infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Gastrointestinal bacterial infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Pyelonephritis chronic | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Intra-abdominal haemorrhage | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Glossitis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Bacterial test positive | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Blood urine present | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Mean cell volume increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Urine protein/creatinine ratio increased | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Electrocardiogram QRS complex prolonged | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Heart rate irregular | Investigations | MedDRA (21.1) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Bundle branch block | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Left ventricular hypertrophy | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Injection site inflammation | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Glucose tolerance impaired | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Snoring | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Poor peripheral circulation | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Thrombophlebitis | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Albuminuria | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Bladder pain | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Renal cyst | Renal and urinary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Meningioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.1) | Systematic Assessment |
| |
| Renal cancer stage I | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Type V hyperlipidaemia | Congenital, familial and genetic disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Acromegaly | Endocrine disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Asthenopia | Eye disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
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.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ionis Pharmaceuticals, Inc | Ionis Pharmaceuticals, Inc | 800-679-4747 | patients@ionisph.com |
| Oct 21, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000172 | Acromegaly |
| ID | Term |
|---|---|
| D001849 | Bone Diseases, Endocrine |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D006964 | Hyperpituitarism |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG004 | Cohort D: IONIS GHR-LRx, 160 mg | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
| OG004 | Cohort D: IONIS GHR-LRx, 160 mg | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
| OG004 | Cohort D: IONIS GHR-LRx, 160 mg | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.
| OG004 | Cohort D: IONIS GHR-LRx, 160 mg | Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
| OG004 |
| Cohort D: IONIS GHR-LRx, 160 mg |
Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks. |
| OG002 | ISIS 766720 High Dose | Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks. |
| OG002 | ISIS 766720 High Dose | Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.
| OG002 | ISIS 766720 High Dose | Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|
Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.
| OG002 | ISIS 766720 High Dose | Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks. |
|
|