C3 glomerulopathy (C3G)

Active Ingredient: Pegcetacoplan

Indication for Pegcetacoplan

Population group: only adolescents (12 years - 18 years old) , adults (18 years old or older)
Therapeutic intent: Curative procedure

Pegcetacoplan is indicated for the treatment of adult and adolescent patients aged 12 to 17 years with C3 glomerulopathy (C3G) in combination with a renin-angiotensin system (RAS) inhibitor, unless RAS inhibitor treatment is not tolerated or contraindicated.

For this indication, competent medicine agencies globally authorize below treatments:

1 080 mg once on Day 1 and Day 4 of each treatment week

For:

Dosage regimens

Intravenous, 1,080 milligrams pegcetacoplan, 2 times weekly.

Detailed description

Pegcetacoplan is administered twice weekly as a 1 080 mg subcutaneous infusion with a commercially available syringe system infusion pump or on-body delivery system. The twice weekly dose should be administered on Day 1 and Day 4 of each treatment week.

C3G is a chronic disease. Discontinuation of this medicinal product is not recommended unless clinically indicated.

Missed dose

If a dose of pegcetacoplan for treatment of C3G is missed, it should be administered as soon as possible, then the regular schedule should be resumed even if this results in an interval of less than 3 days between the replacement dose and the subsequent dose.

Patients with post-transplant recurrent C3G

Diagnosis of post-transplant recurrent C3G should be made based on a renal allograft biopsy. C3G recurrence may be detected in a routine post-transplant biopsy; otherwise, a biopsy should be performed when clinical signs indicate recurrent disease. As done in study APL2-C3G-204, treatment with pegcetacoplan can be started before the onset of clinical signs such as estimated glomerular filtration rate (eGFR) decrease or urine to protein-to-creatine ratio (uPCR) increase. There is limited experience with the use of pegcetacoplan in patients with recurrent C3G after transplantation in clinical studies.

Elderly

Although there were no apparent age-related differences observed in clinical studies, the number of patients aged 65 and over is not sufficient to determine whether they respond differently from younger patients. There is no evidence indicating any special precautions are required for treating an elderly population.

Dosage considerations

Pegcetacoplan should only be administered via subcutaneous administration using a commercially available syringe system infusion pump or on-body delivery system.

When using a syringe system infusion pump, pegcetacoplan should be infused in the abdomen, thighs, hips, or upper arms. Infusion sites should be at least 7.5 cm apart from each other. The infusion sites should be rotated between administrations. The infusion time is approximately 30 minutes (if using two sites) or approximately 60 minutes (if using one site).

When using an on-body delivery system, pegcetacoplan should be infused at a site on the abdomen. The infusion site should be rotated between administrations following the device manufacturer's instructions. The infusion time varies by patient and typically ranges from 30 to 60 minutes.

Infusion into areas where the skin is tender, bruised, red, or hard should be avoided. Infusion into tattoos, scars, or stretch marks should be avoided. The infusion should be started promptly after drawing this medicinal product into the syringe. Administration should be completed within 2 hours after preparing the syringe.

540-1,080 mg initial dose, 648-1,080 mg maintenance dose once on Day 1 and Day 4, based on patient's body weight

For:

Dosage regimens

Regimen A, in case that patient weight is ≥ 50 kg

Subcutaneous, 1,080 milligrams pegcetacoplan, 2 times weekly.

Regimen B, in case that patient weight is ≥ 35 kg and patient weight is < 50 kg

Subcutaneous, 648 milligrams pegcetacoplan, one dose, over the duration of 3 days. Afterwards, subcutaneous, 810 milligrams pegcetacoplan, one dose, over the duration of 3 days. Afterwards, subcutaneous, 810 milligrams pegcetacoplan, 2 times weekly.

Regimen C, in case that patient weight is ≥ 30 kg and patient weight is < 35 kg

Subcutaneous, 540 milligrams pegcetacoplan, one dose, over the duration of 3 days. Afterwards, subcutaneous, 540 milligrams pegcetacoplan, one dose, over the duration of 3 days. Afterwards, subcutaneous, 648 milligrams pegcetacoplan, 2 times weekly.

Detailed description

Pegcetacoplan is administered twice weekly as a subcutaneous infusion with a commercially available syringe system infusion pump or on-body delivery system. The twice weekly dose should be administered on Day 1 and Day 4 of each treatment week.

C3G is a chronic disease. Discontinuation of this medicinal product is not recommended unless clinically indicated.

For adolescent patients, the dosing regimen is based on the patient´s body weight and consists of the following:

Body weightFirst dose
(infusion volume)
Second dose
(infusion volume)
Maintenance dose
(infusion volume)
≥50 kg1 080 mg twice weekly
35 to <50 kg648 mg810 mg810 mg twice weekly
30 to <35 kg540 mg540 mg648 mg twice weekly

Missed dose

If a dose of pegcetacoplan for treatment of C3G is missed, it should be administered as soon as possible, then the regular schedule should be resumed even if this results in an interval of less than 3 days between the replacement dose and the subsequent dose.

Patients with post-transplant recurrent C3G

Diagnosis of post-transplant recurrent C3G should be made based on a renal allograft biopsy. C3G recurrence may be detected in a routine post-transplant biopsy; otherwise, a biopsy should be performed when clinical signs indicate recurrent disease. As done in study APL2-C3G-204, treatment with pegcetacoplan can be started before the onset of clinical signs such as estimated glomerular filtration rate (eGFR) decrease or urine to protein-to-creatine ratio (uPCR) increase. There is limited experience with the use of pegcetacoplan in patients with recurrent C3G after transplantation in clinical studies.

Dosage considerations

Pegcetacoplan should only be administered via subcutaneous administration using a commercially available syringe system infusion pump or on-body delivery system.

When using a syringe system infusion pump, pegcetacoplan should be infused in the abdomen, thighs, hips, or upper arms. Infusion sites should be at least 7.5 cm apart from each other. The infusion sites should be rotated between administrations. The infusion time is approximately 30 minutes (if using two sites) or approximately 60 minutes (if using one site).

When using an on-body delivery system, pegcetacoplan should be infused at a site on the abdomen. The infusion site should be rotated between administrations following the device manufacturer's instructions. The infusion time varies by patient and typically ranges from 30 to 60 minutes.

Infusion into areas where the skin is tender, bruised, red, or hard should be avoided. Infusion into tattoos, scars, or stretch marks should be avoided. The infusion should be started promptly after drawing this medicinal product into the syringe. Administration should be completed within 2 hours after preparing the syringe.

Active ingredient

Pegcetacoplan

Pegcetacoplan is a symmetrical molecule comprised of two identical pentadecapeptides covalently bound to the ends of a linear 40-kDa PEG molecule. The peptide moieties bind to complement C3 and C3b and exert a broad inhibition of the complement cascade. The 40-kDa PEG moiety imparts improved solubility and longer residence time in the body after administration of the medicinal product. Pegcetacoplan binds to complement protein C3 and its activation fragment C3b with high affinity, thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation.

Read more about Pegcetacoplan

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