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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-000675-20 | EudraCT Number | ||
| NCT04522180 | Other Identifier | ClinicalTrials.gov |
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The purpose of this study was to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly.
This was a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants were randomized to 1 of 2 treatment groups to receive IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants entered a 14-week post-treatment (PT) evaluation period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GHR-LRX 120 mg | Experimental | Participants received GHR-LRX 120 mg subcutaneous (SC) injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). |
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| GHR-LRX 160 mg | Experimental | Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GHR-LRX | Drug | GHR-LRX was administered by SC injection. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27 | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Baseline of IGF-1 is defined as the average value of Screening and Day 1. A negative percent change from Baseline indicated improvement. | Baseline to Week 27 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27) | Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's upper limit of normal (ULN). | At Week 27 |
| Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27) |
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Inclusion Criteria:
Males or females with a documented diagnosis of Acromegaly* who are 18 to 75 years old (inclusive) at the time of informed consent.
Have had pituitary surgery (e.g. transsphenoidal) unless there was a contraindication to surgery and are either acromegaly medical treatment naïve, or who had not taken any other acromegaly medications prior to the screening visit as outlined below
At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × 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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States | ||
| Massachusetts General Hospital |
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Participants with acromegaly were enrolled and assigned to receive an initial dose of GHR-LRX 120 mg or GHR-LRX 160 mg up to week 17 (when the first post-baseline IGF-1 results were available). After Week 17, patients may have received a higher dose up to 160 mg for efficacy, if necessary, up to 73 weeks.
Participants were enrolled at 22 investigational sites in United States of America, Estonia, Hungary, Italy, Latvia, Lithuania, Poland, Romania, Russia, and Serbia from 4 January 2021 to 18Jan2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | GHR-LRX 120 mg | Participants received GHR-LRX 120 mg subcutaneous (SC) injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). |
| FG001 | GHR-LRX 160 mg |
| 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 | Aug 30, 2022 |
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Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's ULN. |
| At Week 27 |
| Change From Baseline in Serum IGF-1 Over Time | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative change from baseline indicated improvement. | Up to approximately 80 weeks |
| Percent Change From Baseline in Serum IGF-1 Over Time | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative percent change from Baseline indicated improvement. | Baseline, Week 3, 5, 7, 9, 11, 13, 15, 17, 21, 25, 27, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73 |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Palm Research Center Inc. | Las Vegas | Nevada | 89148 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Endocrinology Associates, Inc | Columbus | Ohio | 43201 | United States |
| Oregon Health & Science University (OHSU) | Portland | Oregon | 97239 | United States |
| East-Tallinn Central Hospital | Tallinn | 10138 | Estonia |
| Tartu University Hospital | Tartu | 50406 | Estonia |
| Debreceni Egyetem Klinikai Kozpont | Debrecen | 4032 | Hungary |
| Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano | Milan | 20122 | Italy |
| Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore | Roma | 00168 | Italy |
| Pauls Stradins Clinical University Hospital | Riga | LV-1002 | Latvia |
| Vaidoto Urbanaviciaus Individuali imone | Alytus | 63246 | Lithuania |
| Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos | Kaunas | 50161 | Lithuania |
| Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii | Warsaw | 03-242 | Poland |
| Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu, | Wroclaw | 50-556 | Poland |
| Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p. | Wroclaw | 51-162 | Poland |
| Centrul Medical Unirea Bucuresti, Endocrinologie | Bucharest | 060044 | Romania |
| I.M. Sechenov Moscow First State Medical University | Moscow | 119146 | Russia |
| Clinical Center of Serbia | Belgrade | 11000 | Serbia |
| Clinical Center of Vojvodina | Novi Sad | 21000 | Serbia |
Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
| Per Protocol Set (Initial Dose) | Per protocol set included all participants that started the study and who completed at least 6 of the 8 doses of GHR-LRX with the first 27 Weeks administered and had no significant protocol deviations that impacted efficacy. Initial dose was the dose received up to Week 17 and maximum dose was the dose received following dose escalation up to Week 73. |
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| Increased Dose From Initial 120mg to Maximum Dose 160mg (Week 17 to Week 45) |
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| COMPLETED | Completed included participants who completed the study treatment. |
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| NOT COMPLETED |
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Safety analysis set included all participants who were randomized and received at least 1 dose of GHR-LRX
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| ID | Title | Description |
|---|---|---|
| BG000 | GHR-LRX 120 mg | Participants received GHR-LRX 120 mg subcutaneous (SC) injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). |
| BG001 | GHR-LRX 160 mg | Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27 | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Baseline of IGF-1 is defined as the average value of Screening and Day 1. A negative percent change from Baseline indicated improvement. | Per protocol set (total dose) included all FAS participants who completed at least 6 of the 8 doses of GHR-LRX with the first 27 Weeks administered and have no significant protocol deviations that would be expected to impact efficacy. Total dose includes results for IGF-1 reduction that combines both 120 mg and 160 mg doses. Analysis based on highest dose received as prespecified in the statistical analysis plan (SAP). | Posted | Mean | Standard Deviation | Percent change | Baseline to Week 27 |
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| Secondary | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27) | Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's upper limit of normal (ULN). | Per protocol set (initial dose) includes all FAS participants who completed at least 6 of the 8 doses of GHR-LRX within the first 27 weeks administered and had no significant protocol deviations that would have been expected to impact efficacy. Here, overall number of participants analyzed signifies the number of participants available for analyses. Analysis based on highest dose received as prespecified in the statistical analysis plan (SAP). | Posted | Number | 95% Confidence Interval | percentage of participants | At Week 27 |
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| Secondary | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27) | Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's ULN. | Per protocol set (initial dose) includes all FAS participants who completed at least 6 of the 8 doses of GHR-LRX within the first 27 weeks administered and had no significant protocol deviations that would have been expected to impact efficacy. Here, overall number of participants analyzed signifies the number of participants available for analyses. Analysis based on highest dose received as prespecified in the statistical analysis plan (SAP). | Posted | Number | 95% Confidence Interval | percentage of participants | At Week 27 |
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| Secondary | Change From Baseline in Serum IGF-1 Over Time | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative change from baseline indicated improvement. | Per protocol set (maximum dose) includes all FAS participants who completed at least 6 of the 8 doses of GHR-LRX within the first 27 weeks administered and had no significant protocol deviations that would have been expected to impact efficacy. Here, 'Number analyzed' signifies the number of participants analyzed at specified time points. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Up to approximately 80 weeks |
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| Secondary | Percent Change From Baseline in Serum IGF-1 Over Time | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative percent change from Baseline indicated improvement. | Per protocol set (maximum dose) includes all FAS participants who completed at least 6 of the 8 doses of GHR-LRX within the first 27 weeks administered and had no significant protocol deviations that would have been expected to impact efficacy. 'Number analyzed' signifies the number of participants analyzed at specified time points. | Posted | Mean | Standard Deviation | percent change | Baseline, Week 3, 5, 7, 9, 11, 13, 15, 17, 21, 25, 27, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73 |
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From Day 1 up to the end of study follow-up (up to week 121).
All participants who were randomized and received at least 1 dose of GHR-LRX. Data for all-cause mortality, serious and non-serious adverse events is reported as per the maximum dose received by participants per arm considering dose escalation was allowed in this study. Adverse events collected based on highest dose received as prespecified in the statistical analysis plan (SAP).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GHR-LRX 120 mg (Safety Set) | Participants received a maximum dose of GHR-LRX 120 mg SC injection once every month for up to 73 weeks with a booster dose administered on Day 15 (Week 3). | 0 | 3 | 1 | 3 | 3 | 3 |
| EG001 | GHR-LRX 160 mg (Safety Set) | Participants received a maximum dose of GHR-LRX 160 mg SC injection once every month for up to 73 weeks with a booster dose administered on Day 15 (Week 3). Due to the length of the study after Week 17, participants received the maximum dose longer than the initial dose. | 0 | 31 | 2 | 31 | 26 | 31 |
| EG002 | GHR-LRX Total (Safety Set) | Overall number of participants (34) analyzed is the number of participants available for analyses. | 0 | 34 | 3 | 34 | 29 | 34 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block second degree | Cardiac disorders | MedDRA24.0 | Systematic Assessment |
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| COVID-19 pneumonia | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Cholecystitis chronic | Hepatobiliary disorders | MedDRA24.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Respiratory tract infection viral | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Asymptomatic COVID-19 | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Pyelonephritis chronic | Infections and infestations | MedDRA24.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA24.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Diverticulum intestinal | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Haematochezia | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA24.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA24.0 | Systematic Assessment |
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| Lipase increased | Investigations | MedDRA24.0 | Systematic Assessment |
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| Urine albumin/creatinine ratio increased | Investigations | MedDRA24.0 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA24.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA24.0 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Rosacea | Skin and subcutaneous tissue disorders | MedDRA24.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA24.0 | Systematic Assessment |
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| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA24.0 | Systematic Assessment |
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| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA24.0 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA24.0 | Systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | MedDRA24.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA24.0 | Systematic Assessment |
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| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA24.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA24.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA24.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA24.0 | Systematic Assessment |
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| Renal cyst | Renal and urinary disorders | MedDRA24.0 | Systematic Assessment |
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| Hepatic cyst | Hepatobiliary disorders | MedDRA24.0 | Systematic Assessment |
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| Hepatic steatosis | Hepatobiliary disorders | MedDRA24.0 | Systematic Assessment |
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| Post procedural hypothyroidism | Injury, poisoning and procedural complications | MedDRA24.0 | Systematic Assessment |
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Principal investigators are not employees of Ionis Pharmaceuticals. Work with CDT to establish the Principal Investigator agreement.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ionis Pharmaceuticals, Inc. | Ionis Pharmaceuticals, Inc. | 760-603-2346 | globalregulatoryaffairs@ionisph.com |
| Nov 20, 2023 |
| Prot_SAP_000.pdf |
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| 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 |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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