Adverse reactions
Safety overview for pediatric GHD. MedDRA system organ class (SOC) and frequency categories are grouped below.
Clinical trial exposure
The safety data of Pegpesen® in pediatric patients with growth hormone deficiency (GHD) came mainly from a combined Phase II/III clinical trial.
- Phase II: 42 pediatric patients with GHD received Pegpesen®; 27 were treated for 2 years.
- Phase III: 261 pediatric patients with GHD received Pegpesen®; 251 were treated for 1 year.
Phase III safety study design (excerpt)
A randomized, open-label, active-controlled, multicenter Phase III trial evaluated Pegpesen® in pediatric participants with GHD aged 3 years and older. Investigational products were given for 52 weeks, followed by a 5-week safety follow-up.
No Very common (≥10%) adverse reactions were reported. The most commonly reported adverse reactions included: injection site reactions (9.6%), alanine aminotransferase increased (1.1%), aspartate aminotransferase increased (1.1%), arthralgia (1.1%), blood thyroid stimulating hormone increased (0.8%), rash (0.8%), eyelid oedema (0.8%), among others.
Injection site reactions (product definition)
Injection site reactions include: injection site atrophy, swelling, erythema, pain, pruritus, induration, reaction, haemorrhage, and hypoaesthesia.
Phase III adverse events by SOC (condensed)
The label presents a full MedDRA table comparing Pegpesen® (0.14 mg/kg/week, N=261) with Norditropin® control (0.245 mg/kg/week, N=130). The following rows capture commonly cited findings; see the detailed product information for the complete matrix.
| System organ class | Pegpesen — common | Pegpesen — uncommon | Norditropin — common |
|---|---|---|---|
| General / administration site | Injection site reactions | Asthenia, fatigue, peripheral swelling | Injection site reactions |
| Investigations | ALT increased, AST increased | TSH increased, cortisol changes, thyroxine changes, others (see detailed labeling) | TSH increased, cortisol decreased |
| Musculoskeletal & connective tissue | Arthralgia | Pain in extremity, myalgia, growing pains, synovitis, muscle hypertrophy, scoliosis | Arthralgia, pain in extremity |
| Nervous system | — | Headache, dizziness, taste disorder | Headache |
| Eye disorders | — | Eyelid oedema, exophthalmos, swelling of eyelid | — |
| Skin | — | Rash | Urticaria |
Phase II second-year observations
After year one (N=31), adverse reaction types were similar to Phase III. In year two (N=39), by SOC: investigations (cortisol decreased, blood corticotrophin decreased); musculoskeletal (growing pains, pain in extremity); skin (rash); metabolic (iron deficiency); general disorders (injection site atrophy).
Immunogenicity
Patients may develop anti-inpegsomatropin antibodies. In the Phase III trial in China, after 52 weeks in pediatric participants, the rates of newly positive anti-drug antibodies for Pegpesen® vs Norditropin® were 0.0% (0/226) vs 26.4% (33/125). Newly positive neutralizing antibodies were 0.0% (0/238) vs 7.9% (10/126), a statistically significant difference (P < 0.0001). No identified clinically significant effect of anti-drug antibodies on safety and efficacy of Pegpesen® was observed over the treatment duration. If other causes cannot explain lack of response, consider detecting anti-inpegsomatropin antibodies.
Growth-hormone class effects
In addition to trial-specific adverse reactions, the label lists events reported with other growth hormone products (frequency often not estimable), including: leukaemia (see precautions); type 2 diabetes and hyperglycaemia; blood insulin increased; paraesthesia and benign intracranial hypertension; arthritis; peripheral and facial oedema.