Acute Hepatic Porphyria, Acute Intermittent Porphyria, Acute Porphyria, ALA Dehydratase Deficient Porphyria (ADP), Hereditary Coproporphyria (HCP), Porphyria, Acute Intermittent, Variegate Porphyria (VP)
Conditions
Keywords
Acute Intermittent Porphyria (AIP), Acute Hepatic Porphyria (AHP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), ALA dehydratase deficient porphyria (ADP) (ALAD), RNAi therapeutic, Porphyria
Brief summary
The purpose of this study is to evaluate the effect of subcutaneous givosiran (ALN-AS1), compared to placebo, on the rate of porphyria attacks in patients with Acute Hepatic Porphyrias (AHP).
Interventions
DRUGGivosiran
Givosiran by SC
DRUGPlacebo
Matching placebo (normal saline \[0.9% NaCl\]) by SC
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 12 years of age * Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, aminolevulinic acid (ALA) dehydratase deficient porphyria) * Elevated urinary or plasma porphobilinogen (PBG) or ALA values within the past year, * Have active disease, with at least 2 documented porphyria attacks within the last 6 months * Willing to discontinue or not initiate the use of prophylactic hemin throughout the study. * Women of child bearing potential must have a negative serum pregnancy test, not be nursing, and use acceptable contraception
Exclusion criteria
* Clinically significant abnormal laboratory results * Anticipated liver transplantation * History of multiple drug allergies or intolerance to subcutaneous injections * Active HIV, hepatitis C virus, or hepatitis B virus infection(s) * History of recurrent pancreatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) | 6 months | Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP | 6 months | The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels. |
| Annualized Rate of Hemin Administration in Participants With AIP | 6 months | Annualized rate of hemin doses was evaluated as annualized days of hemin use. |
| Annualized Rate of Porphyria Attacks in Participants With AHP | 6 months | Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home. |
| Area Under the Curve (AUC) of the Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP | Baseline and 6 months | Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores. |
| Average Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP | Baseline and 6 months | Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. |
| The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP | 3 and 6 months | The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels. |
| Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP | Baseline and 6 months | Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. |
| AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP | Baseline and 6 months | Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores. |
| Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP | Baseline and 6 months | Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. |
| Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP | Baseline and 6 months | The SF-12 is a survey designed for use in patients with multiple chronic conditions. This 12-item scale can be used to assess the physical and mental health of respondents. 10 of the 12 questions are answered on a 5 point likert scale and 2 are answered on a 3 point likert scale. The questions are then scored and weighted into 2 subscales, physical health and mental health. Respondents can have a score that ranges from 0-100 with 100 being the best score and indicating high physical or mental health. A 3 point change in SF-12 score reflects a meaningful difference. A higher score indicates improvement. |
| AUC of the Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP | Baseline and 6 months | Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores. |
Countries
Australia, Bulgaria, Canada, Denmark, Finland, France, Germany, Italy, Japan, Mexico, Netherlands, Poland, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants with acute hepatic porphyrias (AHP) were enrolled at thirty-six sites in Australia, Bulgaria, Canada, Germany, Denmark, Spain, Finland, France, United Kingdom, Italy, Japan, Korea (the Republic of), Mexico, Netherlands, Poland, Sweden, Taiwan and the United States.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo (normal saline \[0.9% NaCl\]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period. | 46 |
| Givosiran Givosiran 2.5 mg/kg administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE Period. | 48 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 6-Month DB + Open-Label Extension Period | Adverse Event | 0 | 0 | 2 | 0 |
| 6-Month DB + Open-Label Extension Period | Death | 0 | 0 | 0 | 1 |
| 6-Month DB + Open-Label Extension Period | Lost to Follow-up | 0 | 0 | 1 | 0 |
| 6-Month DB + Open-Label Extension Period | Patient Desired Lower Dose | 0 | 0 | 0 | 1 |
| 6-Month DB + Open-Label Extension Period | Physician Decision | 0 | 0 | 1 | 0 |
| 6-Month DB + Open-Label Extension Period | Pregnancy | 0 | 0 | 1 | 1 |
| 6-Month DB + Open-Label Extension Period | Withdrawal by Subject | 0 | 0 | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo | Givosiran | Total |
|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 10.5 | 40.1 years STANDARD_DEVIATION 12.1 | 38.8 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 42 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 8 Participants | 15 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized More than One Race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 39 Participants | 73 Participants |
| Sex: Female, Male Female | 41 Participants | 43 Participants | 84 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 48 | 0 / 46 | 1 / 48 | 1 / 94 |
| other Total, other adverse events | 37 / 46 | 43 / 48 | 44 / 46 | 47 / 48 | 91 / 94 |
| serious Total, serious adverse events | 4 / 46 | 10 / 48 | 17 / 46 | 20 / 48 | 37 / 94 |
Outcome results
Primary
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
Time frame: 6 months
Population: AIP participants in the Full Analysis Set (FASAIP): All randomized AIP participants (with identified mutation in the hydroxymethylbilane synthase \[HMBS\] gene) who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) | 12.52 annualized attack rate |
| Givosiran 2.5 mg/kg | Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) | 3.22 annualized attack rate |
Comparison: Negative binomial regression model with treatment group and stratification factors (prior hemin prophylaxis status and historical attack rates) as fixed effects and the logarithm of the follow-up time as an offset variable.p-value: <0.000195% CI: [0.16, 0.41]Negative binomial regression model
Secondary
Annualized Rate of Hemin Administration in Participants With AIP
Annualized rate of hemin doses was evaluated as annualized days of hemin use.
Time frame: 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Hemin Administration in Participants With AIP | 29.71 annualized rate of use |
| Givosiran 2.5 mg/kg | Annualized Rate of Hemin Administration in Participants With AIP | 6.77 annualized rate of use |
Secondary
Annualized Rate of Porphyria Attacks in Participants With AHP
Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
Time frame: 6 months
Population: Full Analysis Set (FAS): All randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Porphyria Attacks in Participants With AHP | 12.26 annualized attack rate |
| Givosiran 2.5 mg/kg | Annualized Rate of Porphyria Attacks in Participants With AHP | 3.35 annualized attack rate |
Secondary
Area Under the Curve (AUC) of the Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP
Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores.
Time frame: Baseline and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Area Under the Curve (AUC) of the Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP | 5.286 score on a scale*week |
| Givosiran 2.5 mg/kg | Area Under the Curve (AUC) of the Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP | -11.514 score on a scale*week |
Secondary
AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores.
Time frame: Baseline and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP | -4.011 score on a scale | Standard Error 3.453 |
| Givosiran 2.5 mg/kg | AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP | 1.481 score on a scale | Standard Error 3.31 |
Secondary
AUC of the Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP
Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores.
Time frame: Baseline and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC of the Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP | -4.208 score on a scale*week | Standard Error 4.689 |
| Givosiran 2.5 mg/kg | AUC of the Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP | -11.148 score on a scale*week | Standard Error 4.501 |
Secondary
Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement.
Time frame: Baseline and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP | -0.181 score on a scale | Standard Error 0.154 |
| Givosiran 2.5 mg/kg | Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP | 0.067 score on a scale | Standard Error 0.147 |
Secondary
Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP
Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement.
Time frame: Baseline and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP | -0.182 score on a scale | Standard Error 0.209 |
| Givosiran 2.5 mg/kg | Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP | -0.502 score on a scale | Standard Error 0.2 |
Secondary
Average Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP
Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement.
Time frame: Baseline and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Average Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP | 0.245 score on a scale |
| Givosiran 2.5 mg/kg | Average Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP | -0.506 score on a scale |
Secondary
Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP
The SF-12 is a survey designed for use in patients with multiple chronic conditions. This 12-item scale can be used to assess the physical and mental health of respondents. 10 of the 12 questions are answered on a 5 point likert scale and 2 are answered on a 3 point likert scale. The questions are then scored and weighted into 2 subscales, physical health and mental health. Respondents can have a score that ranges from 0-100 with 100 being the best score and indicating high physical or mental health. A 3 point change in SF-12 score reflects a meaningful difference. A higher score indicates improvement.
Time frame: Baseline and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP | 1.431 score on a scale | Standard Error 1.22 |
| Givosiran 2.5 mg/kg | Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP | 5.369 score on a scale | Standard Error 1.169 |
Secondary
The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP
The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels.
Time frame: 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP | 49.110 mmol/mol Cr | Standard Error 4.959 |
| Givosiran 2.5 mg/kg | The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP | 12.906 mmol/mol Cr | Standard Error 4.642 |
Secondary
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP
The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels.
Time frame: 3 and 6 months
Population: FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP | Month 3 | 19.965 mmol/mol creatinine (Cr) | Standard Error 1.475 |
| Placebo | The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP | Month 6 | 23.150 mmol/mol creatinine (Cr) | Standard Error 2.534 |
| Givosiran 2.5 mg/kg | The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP | Month 3 | 1.756 mmol/mol creatinine (Cr) | Standard Error 1.413 |
| Givosiran 2.5 mg/kg | The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP | Month 6 | 4.013 mmol/mol creatinine (Cr) | Standard Error 2.352 |