Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Recombinant human hyaluronidase PH20 (rHuPH20), PH20, rHuPH20, recombinant human hyaluronidase, Recombinant human hyaluronidase PH20, Formulation 1, Recombinant human hyaluronidase (rHuPH20), Formulation 2
Hylenex · 6 trials · 6 indications
Glycosylated hemoglobin A1C (HBA1c) levels were measured at baseline (Week 0) and at the end of each treatment period (Week 12 and Week 24). Data are presented by combined treatment group (Lispro-PH20 + Aspart-PH20 = Analog-PH20) and combined comparator drug (Insulin Lispro from both cohorts). Least Squares (LS) means were calculated from mixed effects linear models with treatment (Lispro, Aspart), recombinant human hyaluronidase PH20 (rHuPH20; yes, no), and treatment sequence as fixed effects and participant within treatment sequence as a random effect.
Cutaneous reactions at the patch test sites were scored according to the ICDRG scoring scale as Grade 0 (-)= Negative reaction, Grade 1/2 (?)= Doubtful reaction; faint macular erythema only, Grade 1 (1+)= Weak (nonvesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 2 (2+): Strong (vesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 3 (3+): Extreme positive reaction; bullous reaction Grade NA (IR): Irritant reaction of different types. Participants with positive reaction scores (\>= Grade 1) have been reported in this outcome measure.
Cutaneous reactions at the patch test sites were scored according to the ICDRG scoring scale as Grade 0 (-)= Negative reaction, Grade 1/2 (?)= Doubtful reaction; faint macular erythema only, Grade 1 (1+)= Weak (nonvesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 2 (2+): Strong (vesicular) positive reaction; erythema, infiltration, papules, vesicles, Grade 3 (3+): Extreme positive reaction; bullous reaction Grade NA (IR): Irritant reaction of different types. Participants with positive reaction scores (\>= Grade 1) have been reported in this outcome measure.
Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve \[AUC{0-360}\]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.
Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve \[AUC{0-360}) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 120, 150, 180, 240, 300, and 360 minutes postdose during the euglycemic clamp.
| Arm | Type | Description |
|---|---|---|
| 1 | NO_INTERVENTION | IV Morphine |
| 2 | EXPERIMENTAL | SC Morphine with Hylenex |
| 3 | ACTIVE_COMPARATOR | SC Morphine with Saline |
| Lispro-PH20 / Insulin Lispro | EXPERIMENTAL | All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine. |
| Aspart-PH20 / Insulin Lispro | EXPERIMENTAL | All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine. |
| Lispro-PH20/Insulin lispro | EXPERIMENTAL | All enrolled participants underwent a titration period of 4 to 6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next, participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle. Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (combined: Lispro-PH20), injected SC, pre-meals, with doses titrated to each participant individually. Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually. Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine. |
| Aspart-PH20/Insulin Lispro | EXPERIMENTAL | All enrolled participants underwent a titration period of 4 to 6 weeks in which they received 100 U/mL insulin glulisine, injected SC, pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle. Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 µg/mL rHuPH20 (combined: Aspart-PH20), injected SC, pre-meals, with doses titrated to each participant individually. Insulin lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually. Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine. |
| rHuPH20 | EXPERIMENTAL | Participant's upper back will be divided into 2 equal spaces and will receive Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the nickel sulfate concentration (NSC) (1, 2.5, or 5%) determined at screening, will be applied to the upper space at Day 1. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. An ID injection containing rHuPH20 (3,000 Units \[U\]) will be administered once daily (QD) for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space will be injected intradermally with drug rHuPH20 (3,000 U) at Day 1. Ten minutes after the injections, patches with the NSC (1, 2.5, or 5%) determined at screening will be applied to the injection sites. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. As during pretreatment, an ID injection containing rHuPH20 will be then administered QD for 5 days. |
| Placebo | PLACEBO_COMPARATOR | Participant's upper back will be divided into 2 equal spaces and will receive Regimen 1 and 2 in 4 spaces respectively. In Regimen 1, a single row of 4 patches, each with the NSC (1, 2.5, or 5%) determined at screening, will be applied to the upper space at Day 1. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. An ID injection containing placebo will be administered QD for 5 days at the center of each area of reaction. In Regimen 2, a single row of 4 sites in the lower space will be injected intradermally with placebo at Day 1. Ten minutes after the injections, patches with the NSC (1, 2.5, or 5%) determined at screening will be applied to the injection sites. After 48 hours, the patches will be removed and the reactions will be graded on the ICDRG scale. As during pretreatment, an ID injection containing placebo will be then administered QD for 5 days. |
| Stage 1: Insulin aspart first, then insulin aspart-rHuPH20 | ACTIVE_COMPARATOR | Participants first received 0.15 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4. After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8. |
| Stage 1: Insulin aspart-rHuPH20 first, then insulin aspart | ACTIVE_COMPARATOR | Participants first received 0.15 units per kilogram (U/kg) insulin aspart and 5 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) (insulin aspart-rHuPH20) coadministered as a continuous subcutaneous insulin infusion (CSII), for 4 days (Days 1-4; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2 and 4. After a 5- to 14-day washout period, participants received 0.15 U/kg insulin aspart alone as a CSII, for 4 days (Days 5-8; Period 2), including during a 6-hr euglycemic clamp on Days 6 and 8. |
| Stage 3: Insulin aspart first, then insulin aspart + rHuPH20 | ACTIVE_COMPARATOR | Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6-hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a sham injection was administered 2.5 hr prior to the 6-hr euglycemic clamp. After a 5- to 14-day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the 6-hr euglycemic clamp. |
| Stage 3: Insulin aspart + rHuPH20 first, then insulin aspart | ACTIVE_COMPARATOR | Participants first received 0.12 units per kilogram (U/kg) insulin aspart administered as a continuous subcutaneous insulin infusion (CSII), for 5 days (Days 1-5; Period 1), including during a 6- hour (hr) euglycemic clamp on Days 2, 3, and 5. On Day 2 only, a 1.0-milliliter (mL) subcutaneous (SC) injection of 1.25 micrograms per milliliter (μg/mL) recombinant human hyaluronidase PH20 (rHuPH20) was administered 2.5 hr prior to the euglycemic clamp . After a 5- to 14- day washout period, participants received 0.12 U/kg insulin aspart administered as a CSII, for 5 days (Days 6-10; Period 2), including during a 6-hr euglycemic clamp on Days 7, 8, and 10. On Day 7 only, a sham injection was administered 2.5 hr prior to the 6-hour euglycemic clamp. |
| Stage 1: rHuPH20 plus ZA | EXPERIMENTAL | Participants will receive one of several dose/concentrations of recombinant human hyaluronidase PH20 (rHuPH20) with zoledronic acid (ZA). |
| Stage 2: ZA | EXPERIMENTAL | Participants will receive a dose/concentration of ZA administered without rHuPH20. |
| Stage 3: rHuPH20 plus ZA | EXPERIMENTAL | Participants will receive one of several dose/concentrations of rHuPH20 with ZA. |
| Stage 4: ZA | EXPERIMENTAL | Participants will receive an intravenous (IV) dose of 5 milligrams (mg) ZA. |
| Stage 4: ZA with rHuPH20 | EXPERIMENTAL | Participants will receive a subcutaneous (SC) dose of ZA with rHuPH20. |
| Name | Type | Description |
|---|---|---|
| Hylenex | DRUG | Add Hylenex to SC injection of Morphine |
| Insulin lispro | DRUG | - |
| recombinant human hyaluronidase PH20 | DRUG | - |
| Insulin aspart | DRUG | - |
| Insulin glulisine | DRUG | - |
| Insulin glargine | DRUG | - |
| rHuPH20 | DRUG | 0.25 milliliter (mL) Intradermal (ID) syringe push bolus injection of rHuPH20 |
| Placebo | DRUG | 0.25 mL ID syringe push bolus injection of placebo control |
| Recombinant human hyaluronidase PH20 (rHuPH20) | DRUG | - |
| zoledronic acid | DRUG | subcutaneous injection |
Inclusion Criteria: 1. Males or females at least 18 years of age who are patients of San Diego Hospice \& Palliative Care or recruited through San Diego Hospice \& Palliative Care or the UCSD Center for Pain and Palliative Medicine. 2. During the treatment days of the study, on opioid therapy other...
Hylenex is an investigational small molecule developed by Halozyme Therapeutics for pain. It has been studied in a Phase 3 trial in patients with pain, though no active trials are currently listed. The completed trial enrolled 13 adults aged 18 years and older in the United States.
Hylenex is developed by Halozyme Therapeutics, Inc., which trades under the ticker HALO. The company is responsible for the clinical development of Hylenex in pain indications.
Hylenex is in Phase 3 development for pain. One Phase 3 trial has been completed, and there are currently no active trials listed. Hylenex is investigational and has not been approved by the FDA for any indication.
Hylenex has been evaluated in one completed Phase 3 trial, NCT00593281, titled INFUSE Morphine Study. The trial enrolled 13 participants with pain in the United States. It was randomized, double-blind, and active-controlled, with participants aged 18 years and older.
Hylenex is not FDA approved. It is an investigational small molecule still in clinical development, with a completed Phase 3 trial in pain. No approval has been granted for any indication based on the available development information.