Acromegaly
Conditions
Keywords
acromegaly, IONIS-GHR-LRx
Brief summary
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.
Detailed description
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.
Interventions
DRUGGHR-LRX
GHR-LRX was administered by SC injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females with a documented diagnosis of Acromegaly\* who are 18 to 75 years old (inclusive) at the time of informed consent. 2. 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 * bromocriptine: 2 weeks * cabergoline: 4 weeks * quinagolide: 4 weeks * octreotide daily injection (SC) or oral formulation: 4 weeks * pegvisomant: 4 weeks * octreotide LAR: 3 months * pasireotide LAR: 4 months * lanreotide (all formulations): 3 months 3. At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × 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 3 months before the trial, and/or planning to receive surgery during the trial 2. Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial 3. Participants with a pituitary tumor that, per Investigator judgment, is worsening (e.g., either growing or at risk of compressing or abutting the optic chiasm or other vital structures) as assessed by pituitary/sellar MRI protocol at Screening or within 3 months of Screening. CT scan is allowed if MRI is contraindicated 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. Symptomatic cholelithiasis, and/or choledocholithiasis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27) | At 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). |
| Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27) | At Week 27 | Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's ULN. |
| Change From Baseline in Serum IGF-1 Over Time | Up to approximately 80 weeks | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative change from baseline indicated improvement. |
| Percent Change From Baseline in Serum IGF-1 Over Time | 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 | IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative percent change from Baseline indicated improvement. |
Countries
Estonia, Hungary, Italy, Latvia, Lithuania, Poland, Romania, Russia, Serbia, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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 by arm
| Arm | Count |
|---|---|
| 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). | 3 |
| 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). | 31 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event or Serious Adverse event | 1 | 3 |
| Overall Study | Investigator judgement | 3 | 4 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Reason not specified | 8 | 5 |
| Overall Study | Voluntary withdrawal | 1 | 0 |
Baseline characteristics
| Characteristic | GHR-LRX 160 mg | Total | GHR-LRX 120 mg |
|---|---|---|---|
| Age, Continuous | 51.9 Years STANDARD_DEVIATION 11.76 | 52.9 Years STANDARD_DEVIATION 11.68 | 63.0 Years STANDARD_DEVIATION 3.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 34 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 33 Participants | 3 Participants |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 1 Participants |
| Sex: Female, Male Male | 15 Participants | 17 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 31 | 0 / 34 |
| other Total, other adverse events | 3 / 3 | 26 / 31 | 29 / 34 |
| serious Total, serious adverse events | 1 / 3 | 2 / 31 | 3 / 34 |
Outcome results
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.
Time frame: Baseline to Week 27
Population: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27 | -6.20 Percent change | Standard Deviation 10.803 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27 | -7.16 Percent change | Standard Deviation 20.1 |
| GHR-LRX Total (Per Protocol Set) | Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27 | -7.09 Percent change | Standard Deviation 19.402 |
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.
Time frame: Up to approximately 80 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 49 | -81.75 nanograms per milliliter (ng/mL) | Standard Deviation 109.955 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 21 | -123.25 nanograms per milliliter (ng/mL) | Standard Deviation 136.118 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 9 | -109.00 nanograms per milliliter (ng/mL) | Standard Deviation 111.959 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 45 | -86.75 nanograms per milliliter (ng/mL) | Standard Deviation 175.009 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 25 | -99.75 nanograms per milliliter (ng/mL) | Standard Deviation 126.926 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 73 | -1.00 nanograms per milliliter (ng/mL) | — |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 41 | -93.25 nanograms per milliliter (ng/mL) | Standard Deviation 146.018 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 27 | -58.75 nanograms per milliliter (ng/mL) | Standard Deviation 87.328 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 61 | -125.75 nanograms per milliliter (ng/mL) | Standard Deviation 199.051 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 37 | -98.75 nanograms per milliliter (ng/mL) | Standard Deviation 179.252 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 29 | -90.25 nanograms per milliliter (ng/mL) | Standard Deviation 126.219 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 11 | -157.67 nanograms per milliliter (ng/mL) | Standard Deviation 144.923 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 33 | -75.25 nanograms per milliliter (ng/mL) | Standard Deviation 110.662 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 69 | -22.00 nanograms per milliliter (ng/mL) | — |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 57 | -73.75 nanograms per milliliter (ng/mL) | Standard Deviation 91.57 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 13 | -89.67 nanograms per milliliter (ng/mL) | Standard Deviation 130.989 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 7 | -84.33 nanograms per milliliter (ng/mL) | Standard Deviation 133.829 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | At Week 3 | -30.00 nanograms per milliliter (ng/mL) | Standard Deviation 44.908 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 15 | -112.00 nanograms per milliliter (ng/mL) | Standard Deviation 112.618 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | At Week 5 | -50.67 nanograms per milliliter (ng/mL) | Standard Deviation 101.186 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 53 | -90.25 nanograms per milliliter (ng/mL) | Standard Deviation 158.745 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 17 | -89.33 nanograms per milliliter (ng/mL) | Standard Deviation 136.433 |
| GHR-LRX 120 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 65 | 74.00 nanograms per milliliter (ng/mL) | — |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 53 | -68.71 nanograms per milliliter (ng/mL) | Standard Deviation 81.822 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | At Week 3 | 5.03 nanograms per milliliter (ng/mL) | Standard Deviation 49.932 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | At Week 5 | -45.53 nanograms per milliliter (ng/mL) | Standard Deviation 87.817 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 7 | -39.46 nanograms per milliliter (ng/mL) | Standard Deviation 80.258 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 9 | -25.28 nanograms per milliliter (ng/mL) | Standard Deviation 93.924 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 11 | -14.28 nanograms per milliliter (ng/mL) | Standard Deviation 64.463 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 13 | -38.01 nanograms per milliliter (ng/mL) | Standard Deviation 68.885 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 15 | -28.97 nanograms per milliliter (ng/mL) | Standard Deviation 79.942 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 17 | 136.433 nanograms per milliliter (ng/mL) | Standard Deviation 88.212 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 21 | -51.91 nanograms per milliliter (ng/mL) | Standard Deviation 92.746 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 25 | -36.99 nanograms per milliliter (ng/mL) | Standard Deviation 78.236 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 27 | -49.45 nanograms per milliliter (ng/mL) | Standard Deviation 112.579 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 29 | -40.25 nanograms per milliliter (ng/mL) | Standard Deviation 80.174 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 33 | -53.12 nanograms per milliliter (ng/mL) | Standard Deviation 72.494 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 37 | -32.55 nanograms per milliliter (ng/mL) | Standard Deviation 107.499 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 41 | -43.12 nanograms per milliliter (ng/mL) | Standard Deviation 97.911 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 45 | -52.80 nanograms per milliliter (ng/mL) | Standard Deviation 110.595 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 49 | -64.59 nanograms per milliliter (ng/mL) | Standard Deviation 105.493 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 57 | -59.43 nanograms per milliliter (ng/mL) | Standard Deviation 90.08 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 61 | -83.08 nanograms per milliliter (ng/mL) | Standard Deviation 112.428 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 65 | -103.30 nanograms per milliliter (ng/mL) | Standard Deviation 102.76 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 69 | -85.59 nanograms per milliliter (ng/mL) | Standard Deviation 53.018 |
| GHR-LRX 160 mg (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 73 | -91.18 nanograms per milliliter (ng/mL) | Standard Deviation 79.166 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 65 | -88.52 nanograms per milliliter (ng/mL) | Standard Deviation 110.54 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 45 | -55.75 nanograms per milliliter (ng/mL) | Standard Deviation 112.282 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 17 | -41.82 nanograms per milliliter (ng/mL) | Standard Deviation 92.034 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | At Week 5 | -46.01 nanograms per milliliter (ng/mL) | Standard Deviation 87.341 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 49 | -66.23 nanograms per milliliter (ng/mL) | Standard Deviation 103.184 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 15 | -37.28 nanograms per milliliter (ng/mL) | Standard Deviation 85.124 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 13 | -42.85 nanograms per milliliter (ng/mL) | Standard Deviation 75.013 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 53 | -70.86 nanograms per milliliter (ng/mL) | Standard Deviation 85.793 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 11 | -27.73 nanograms per milliliter (ng/mL) | Standard Deviation 83.134 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 73 | -79.91 nanograms per milliliter (ng/mL) | Standard Deviation 79.928 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 57 | -60.93 nanograms per milliliter (ng/mL) | Standard Deviation 87.744 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 9 | -33.13 nanograms per milliliter (ng/mL) | Standard Deviation 96.909 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 69 | -78.53 nanograms per milliliter (ng/mL) | Standard Deviation 53.934 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 29 | -44.25 nanograms per milliliter (ng/mL) | Standard Deviation 82.145 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 61 | -88.10 nanograms per milliliter (ng/mL) | Standard Deviation 117.206 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 33 | -54.89 nanograms per milliliter (ng/mL) | Standard Deviation 73.247 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 27 | -50.16 nanograms per milliliter (ng/mL) | Standard Deviation 109.415 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 7 | -43.66 nanograms per milliliter (ng/mL) | Standard Deviation 84.558 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 37 | -37.85 nanograms per milliliter (ng/mL) | Standard Deviation 110.76 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 25 | -41.82 nanograms per milliliter (ng/mL) | Standard Deviation 81.034 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | At Week 3 | 1.74 nanograms per milliliter (ng/mL) | Standard Deviation 49.896 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 41 | -47.13 nanograms per milliliter (ng/mL) | Standard Deviation 99.341 |
| GHR-LRX Total (Per Protocol Set) | Change From Baseline in Serum IGF-1 Over Time | Week 21 | -57.39 nanograms per milliliter (ng/mL) | Standard Deviation 95.03 |
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.
Time frame: At Week 27
Population: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GHR-LRX 120 mg (Per Protocol Set) | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27) | 0 percentage of participants |
| GHR-LRX 160 mg (Per Protocol Set) | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27) | 0 percentage of participants |
| GHR-LRX Total (Per Protocol Set) | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27) | 0 percentage of participants |
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).
Time frame: At Week 27
Population: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GHR-LRX 120 mg (Per Protocol Set) | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27) | 0 percentage of participants |
| GHR-LRX 160 mg (Per Protocol Set) | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27) | 0 percentage of participants |
| GHR-LRX Total (Per Protocol Set) | Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27) | 0 percentage of participants |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 45 | -3.24 percent change | Standard Deviation 29.617 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 21 | -19.07 percent change | Standard Deviation 8.695 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 65 | 35.41 percent change | — |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 41 | -8.89 percent change | Standard Deviation 19.345 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 25 | -13.28 percent change | Standard Deviation 12.01 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 9 | -17.43 percent change | Standard Deviation 11.285 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 37 | -6.25 percent change | Standard Deviation 27.791 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 27 | -6.20 percent change | Standard Deviation 10.803 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 73 | -0.48 percent change | — |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 33 | -8.10 percent change | Standard Deviation 13.484 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 29 | -10.55 percent change | Standard Deviation 14.242 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 61 | -11.72 percent change | Standard Deviation 26.723 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 11 | -26.56 percent change | Standard Deviation 15.966 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 5 | -5.67 percent change | Standard Deviation 12.296 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 57 | -10.11 percent change | Standard Deviation 8.205 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 13 | -10.32 percent change | Standard Deviation 17.934 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 3 | -3.73 percent change | Standard Deviation 5.072 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 53 | -6.37 percent change | Standard Deviation 23.892 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 15 | -17.81 percent change | Standard Deviation 13.377 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 69 | -10.53 percent change | — |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 49 | -10.12 percent change | Standard Deviation 11.603 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 17 | -9.36 percent change | Standard Deviation 20.529 |
| GHR-LRX 120 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 7 | -9.57 percent change | Standard Deviation 16.297 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 53 | -14.81 percent change | Standard Deviation 19.811 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 3 | 2.64 percent change | Standard Deviation 11.936 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 5 | -8.28 percent change | Standard Deviation 18.158 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 9 | -2.95 percent change | Standard Deviation 16.995 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 11 | -1.15 percent change | Standard Deviation 16.235 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 13 | -6.35 percent change | Standard Deviation 16.837 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 15 | -5.40 percent change | Standard Deviation 21.168 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 17 | -4.59 percent change | Standard Deviation 20.631 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 21 | -9.98 percent change | Standard Deviation 22.994 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 25 | -6.58 percent change | Standard Deviation 16.164 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 27 | -7.16 percent change | Standard Deviation 20.1 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 29 | -7.92 percent change | Standard Deviation 18.173 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 33 | -10.10 percent change | Standard Deviation 16.351 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 37 | -4.29 percent change | Standard Deviation 25.161 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 41 | -9.01 percent change | Standard Deviation 23.25 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 45 | -8.26 percent change | Standard Deviation 23.791 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 49 | -12.83 percent change | Standard Deviation 22.932 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 7 | -7.16 percent change | Standard Deviation 16.637 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 57 | -10.50 percent change | Standard Deviation 19.795 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 61 | -18.94 percent change | Standard Deviation 25.675 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 65 | -21.36 percent change | Standard Deviation 25.392 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 69 | -23.32 percent change | Standard Deviation 14.391 |
| GHR-LRX 160 mg (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 73 | -22.62 percent change | Standard Deviation 20.556 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 3 | 2.04 percent change | Standard Deviation 11.571 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 45 | -7.82 percent change | Standard Deviation 23.59 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 15 | -6.64 percent change | Standard Deviation 20.698 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 65 | -16.63 percent change | Standard Deviation 29.235 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 49 | -12.57 percent change | Standard Deviation 21.924 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 13 | -6.72 percent change | Standard Deviation 16.679 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 5 | -8.04 percent change | Standard Deviation 17.554 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 53 | -13.97 percent change | Standard Deviation 19.697 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 11 | -3.54 percent change | Standard Deviation 17.638 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 73 | -19.85 percent change | Standard Deviation 20.578 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 57 | -10.46 percent change | Standard Deviation 18.763 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 9 | -4.31 percent change | Standard Deviation 16.955 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 29 | -8.13 percent change | Standard Deviation 17.656 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 27 | -7.09 percent change | Standard Deviation 19.402 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 69 | -21.89 percent change | Standard Deviation 14.12 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 33 | -9.94 percent change | Standard Deviation 15.905 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 25 | -7.10 percent change | Standard Deviation 15.794 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 61 | -18.09 percent change | Standard Deviation 25.044 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 37 | -4.45 percent change | Standard Deviation 24.755 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 21 | -10.68 percent change | Standard Deviation 22.261 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 7 | -7.39 percent change | Standard Deviation 16.36 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 41 | -9.00 percent change | Standard Deviation 22.608 |
| GHR-LRX Total (Per Protocol Set) | Percent Change From Baseline in Serum IGF-1 Over Time | At Week 17 | -5.04 percent change | Standard Deviation 20.338 |