Trogarzo

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trogarzo 200 mg concentrate for solution for infusion 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 200 mg of ibalizumab (in 1.33 mL of solution). 
 
Ibalizumab is produced in murine myeloma non-secreting (NS0) cells by recombinant DNA 
technology. 
 
For the full list of excipients, see section 6.1. 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
Colourless to slightly yellow, clear to slightly opalescent aqueous solution. 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Trogarzo, in combination with other antiretroviral(s), is indicated for the treatment of adults infected 
with multidrug resistant HIV-1 infection for whom it is otherwise not possible to construct a 
suppressive antiviral regimen (see section 5.1).  
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
The recommended dose of ibalizumab is a single loading dose of 2,000 mg followed by a maintenance 
dose of 800 mg every 2 weeks.  
 
If the treating physician determines there is no additional clinical benefit for the patient in terms of 
viral load reduction, discontinuation of ibalizumab treatment should be considered, see section 5.1. 
 
Missed dose 
If a maintenance dose (800 mg) of ibalizumab is missed by 3 days or longer beyond the scheduled 
dosing day, a loading dose (2,000 mg) should be administered as early as possible. Resume 
maintenance dosing (800 mg) every 2 weeks thereafter. 
 
Elderly 
The safety and efficacy of ibalizumab in geriatric patients (≥ 65 years of age) have not been 
established.  
 
Paediatric population 
The safety and efficacy of ibalizumab in children under the age of 18 years have not yet been 
established. No data are available. 
 



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Method of administration  
 
Intravenous use 

Diluted ibalizumab solution should be administered by a healthcare professional. 

Ibalizumab should be administered as an intravenous infusion. Ibalizumab should not be administered 
as an intravenous push or bolus. 

The duration of the first infusion (loading dose) should be no less than 30 minutes. If no infusion-
associated adverse reactions have occurred, the duration of the subsequent infusions (maintenance 
doses) can be decreased to no less than 15 minutes. 

After the infusion is complete, flush with 30 mL of sodium chloride 9 mg/mL (0.9%) solution for 
injection.  

All patients must be observed during and for 1 hour after completion of ibalizumab administration for 
at least the first infusion. If a reaction occurs, the infusion should be discontinued and appropriate 
medical therapies should be administered. Prophylactic medication is not warranted prior to each 
infusion. If the patient does not experience an infusion-associated adverse reaction, the post-infusion 
observation time can be reduced to 15 minutes thereafter.  

For instructions on dilution of the medicinal product before administration, see section 6.6.  
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Transmission of HIV 
 
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission 
should be taken in accordance with national guidelines. 
 
Immune reconstitution inflammatory syndrome (IRIS) 
 
In HIV-infected patients with severe immune deficiency at the time of initiation of combination 
antiretroviral therapy (cART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of cART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and 
pneumocystis jiroveci pneumonia. Any inflammatory symptoms should be evaluated and treatment 
instituted when necessary. IRIS was reported in 2 subjects out of 153 treated with ibalizumab in Phase 
2b and 3 clinical studies (see section 4.8).   
 
Excipients with known effect 
 
Ibalizumab contains less than 1 mmol sodium (23 mg) in each loading dose of 2,000 mg or 
maintenance dose of 800 mg and therefore is essentially sodium-free.  



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4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. Based on the mechanism of action and target-mediated 
drug disposition of ibalizumab, it is not expected that ibalizumab will have pharmacokinetic drug-drug 
interactions with other medicinal products.  
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
It is recommended that women of childbearing potential use an effective method of contraception 
during treatment.  
 
Pregnancy 
 
There are no data from the use of ibalizumab in pregnant women.  
 
Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). 
 
Human immunoglobulin (IgG) is known to cross the placental barrier. Ibalizumab is not recommended 
during pregnancy. 
 
Breast-feeding 
 
It is unknown whether ibalizumab/metabolites are excreted in human milk. Human IgG is known to be 
excreted in breast milk during the first days after birth, which is decreasing to low concentrations soon 
afterwards; consequently, a risk to breast-fed infants cannot be excluded during this short period and 
ibalizumab should not be used during breast-feeding.  

In order to avoid transmission of HIV to the infant it is recommended that HIV infected women do not 
breast-feed their infants under any circumstances. 

Fertility 
 
There are no data on the effects of ibalizumab on human fertility.  
 
4.7 Effects on ability to drive and use machines 
 
Ibalizumab has a minor influence on the ability to drive and use machines. Dizziness, nausea, fatigue 
and headache have been reported during treatment with ibalizumab (see section 4.8). Patients 
experiencing these symptoms should be advised to use caution when driving or using machines until 
symptoms abate. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reactions were rash (9.2%), diarrhoea (3.9%), dizziness (3.9%), 
headache (3.9%), nausea (3.9%), fatigue (2.0%) and vomiting (2.0%).  

Tabulated list of adverse reactions 
 
A tabulated list of adverse reactions is presented in Table 1. Frequencies are defined as very common 
(≥1/10); common (≥1/100 to < 1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); 
very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each 
frequency grouping, adverse reactions are presented in the order of decreasing seriousness. 



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Table 1. Tabulated summary of adverse reactions associated with ibalizumab  

System organ class Adverse reaction frequency*                    
Immune system disorders hypersensitivity, immune reconstitution 

inflammatory syndrome (see below and section 4.4) 
Uncommon 

Nervous system disorders dizziness, headache, paraesthesia Common 
tremor Uncommon 

Cardiac disorders ventricular extrasystoles, electrocardiogram 
abnormal 

Uncommon 

Vascular disorders hypertension, labile hypertension, orthostatic 
hypotension 

Uncommon 

Gastrointestinal disorders diarrhoea, nausea, vomiting Common 
dry mouth Uncommon 

Skin and subcutaneous tissue 
disorders 

rash**, dermatitis, dry skin  Common 
papule, pruritus, erythema nodosum Uncommon 

General disorders and 
administration site conditions 

fatigue Common 
feeling hot Uncommon 

Injury, poisoning and 
procedural complications 

contusion Uncommon 

* Frequency was calculated based on 24 weeks of safety data from 153 subjects enrolled in Phase 2b study TMB-202 
(n = 113) and Phase 3 study TMB-301 (n=40), as well as on at least 48 weeks of safety data from 27 subjects from TMB-301 
that rolled-over into expanded access study TMB-311.  
**Includes pooled terms “rash”, “rash erythematous”, “rash generalized”, “rash macular”, “rash maculopapular”, “rash 
pruritic” and “rash papular”. 
 
Description of selected adverse reactions 
 
Rash 
Rashes were common. In general, rashes had an early onset (i.e. within 1 to 3 weeks of the first dose of 
ibalizumab), were mild to moderate in intensity, and resolved within 1-3 weeks with continued 
ibalizumab administration. In case of rash, it is recommended that the patient be monitored and 
symptomatic therapy be initiated when appropriate (e.g. cortisteroids and/or anti-histamine medicinal 
products). 
 
Out of the 153 subjects in Phase 2b and 3 clinical studies, one subject experienced a severe rash 
(non-serious). This subject had 8 adverse reactions of rash, including 1 event of macular rash, 1 event 
of generalized rash and 6 events of maculo-papular rash at different times during treatment with 
ibalizumab. No action was taken with ibalizumab in response to these events. 
 
Immune reconstitution inflammatory syndrome (IRIS) 
Out of 153 subjects, two subjects developed immune reconstitution inflammatory syndrome (IRIS; see 
section 4.4) manifested as an exacerbation of progressive multifocal leukoencephalopathy (serious) 
and of cryptococcal cutaneous infection (serious), respectively. Both subjects were discontinued from 
ibalizumab treatment. 
 
Hypersensitivity 
One subject out of 153 was reported to have hypersensitivity (allergic reaction) on Day 21 (i.e. 7 days 
after the 2nd infusion of ibalizumab). As a result, ibalizumab was discontinued.  
 
Immunogenicity 
All 153 subjects enrolled in Phase 2b and 3 clinical trials were tested for the presence of 
anti-ibalizumab IgG antibodies throughout their participation. Only one subject was found to have 
anti-ibalizumab antibodies. The subject had no adverse reactions associated with the positive 
immunogenicity result. The subject received ibalizumab therapy for an additional 1.5 years before 
discontinuing voluntarily with an undetectable viral load (<50 copies/mL).  



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Laboratory abnormalities 
Grade 3 creatinine elevations occurred frequently in subjects with underlying renal disease, risk factors 
for renal disease, and/or in subjects taking concomitant medications known to be nephrotoxic. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no known antidote to ibalizumab overdose. In case of overdose, it is recommended that the 
patient be monitored for any signs or symptoms of adverse reactions and given appropriate 
symptomatic treatment. Standard supportive measures should be applied as required, including 
monitoring of vital signs as well as observation of the clinical status of the patient. 

5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, other antivirals. ATC code: J05AX23 
 
Mechanism of action 

Ibalizumab, a humanized monoclonal antibody of immunoglobulin G type 4 (IgG4), is a CD4 domain 
2-directed HIV-1 inhibitor. Ibalizumab blocks HIV-1 from infecting CD4+ T cells by binding to 
domain 2 of CD4 and interfering with the post-attachment steps required for the entry of HIV-1 virus 
particles into host cells and preventing the viral transmission that occurs via cell-cell fusion. 

Epitope mapping studies indicate that ibalizumab binds to a conformational epitope located primarily 
in domain 2 of the extracellular portion of the CD4 receptor. This epitope is positioned on the surface 
of CD4 opposite to the site in domain 1 that is required for CD4 binding of the MHC class II 
molecules and, therefore, does not interfere with CD4-mediated immune functions.  

Ibalizumab is active against HIV-1 group M isolates (subtypes A, B, C, D, E, or O). It is also active 
against HIV-1 resistant to currently approved antiretroviral medicinal products and exhibits 
antiretroviral activity against R5-tropic, X4-tropic, and dual-tropic HIV-1. 

Phenotypic and genotypic test results revealed no evidence of cross-resistance between ibalizumab and 
any of the approved classes of anti-retroviral medicinal products.  

Resistance 

Decreased susceptibility to ibalizumab, as defined by a decrease in Maximum Percent Inhibition 
(MPI), has been observed in most subjects experiencing virologic failure and may be associated with 
genotypic changes in the HIV-1 envelope coding sequence that results in the loss of potential N-linked 
glycosylation sites (PNGS) in the V5 loop of gp120. No relevant remaining effect of ibalizumab is 
expected in cases of resistance development. Decreased susceptibility to ibalizumab was a finding in 
the majority of patients who experienced virologic failure up to week 24 in the pivotal study. 

Decreased susceptibility to ibalizumab does not alter susceptibility to other approved agents and does 
not result in the selection of CD4-independent viral isolates.  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Clinical efficacy and safety 

Trial TMB-301 
Phase 3 trial TMB-301 was a single arm, multicenter clinical trial conducted in 40 heavily 
treatment-experienced HIV-infected subjects with multidrug resistant HIV-1. Subjects were required 
to have a viral load greater than 1,000 copies/mL and documented resistance to at least one 
antiretroviral medication from three classes of antiretroviral medications as measured by resistance 
testing. Subjects must have been treated with antiretrovirals for at least 6 months and be failing or had 
recently failed therapy (i.e., in the last 8 weeks). 

The trial was composed of three discrete periods: 
 

• Control period (Day 0 to Day 6): Subjects were either monitored on their current failing 
therapy or received no therapy if they had failed and discontinued treatment within the 
8 weeks preceding screening. This was an observational period to establish baseline HIV viral 
load.  

• Functional monotherapy period (Day 7 to Day 13): All subjects received a 2,000 mg loading 
dose of ibalizumab on Day 7. Subjects on a failing ART regimen continued to receive their 
failing regimen in addition to the loading dose of ibalizumab. This period was to establish the 
virologic activity of ibalizumab.    

• Maintenance period (Day 14 to Week 25): On Day 14 of the treatment period, viral load was 
assessed for the primary endpoint, and thereafter the background regimen was optimized to 
include at least one drug to which the subject’s virus was susceptible. The use of an 
investigational drug as a component of the optimized background regimen was allowed. 
Beginning at Day 21, an 800 mg maintenance dose of ibalizumab was administered every two 
weeks through Week 25. This period was to establish the safety and durability of virologic 
suppression of ibalizumab when used in combination with an optimized background regimen. 
 

The majority of subjects in Trial TMB-301 were male (85%), white (55%) and between 23 and 
65 years of age (mean [SD] age: 50.5 [11.0] years). At Baseline, median [Min - Max] viral load and 
CD4+ T cell counts were 35,350 [304 - 743,000] copies/mL and 73 [0 - 676] cells/mm3, respectively. 
The subjects were heavily treatment-experienced: 53% of participants had been treated with 10 or 
more antiretroviral drugs prior to trial enrolment; 98% percent had been treated with NRTIs, 98% with 
PIs, 80% with NNRTIs, 78% with INSTIs, 30% with gp41 fusion inhibitors, and 20% with CCR5 co-
receptor antagonists.   

The primary efficacy endpoint was the proportion of subjects achieving a ≥ 0.5 log10 decrease in viral 
load from the beginning to the end of the “Functional monotherapy period” as compared to the 
proportion of subjects achieving a ≥ 0.5 log10 decrease from the beginning to the end of the “Control 
period”, as defined above.  The results of the primary endpoint analysis are shown in Table 2 below.   

Table 2. Proportion of subjects achieving a ≥ 0.5 log10 decrease in viral load at the end of the 
control and functional monotherapy periods  

 Proportion of subjects achieving a ≥ 0.5 log10 
decrease in viral load 

N=40 
95% CI* 

End of control period  1/40 (3%) 0.06%, 13% 

End of functional monotherapy 
period  

33/40 (83%)**  67%, 93% 

*exact 95% confidence interval 
** p < 0.0001 based on McNemar’s test comparing the proportion of subjects achieving ≥ 0.5 log10 decrease in viral load at 
the end of the control and functional monotherapy periods. 
 
Fifty-five percent of subjects had a ≥ 1 log10 reduction in viral load, and 48% of subjects had a ≥ 
2 log10 reduction in viral load at Week 25. An increase in the mean number of CD4+ T-cells of 
62 cells/mm3 was observed from Baseline to Week 25 (Intent-To-Treat (ITT) analysis). Week 25 



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outcomes are shown in Table 3. Subjects with baseline CD4 counts < 50 cells/mm3 were less likely to 
achieve a HIV-1 RNA of < 200 copies/mL (or < 50 copies/mL) than subjects with > 50 cells/mm3. 

Table 3. Virologic response at week 25 by baseline CD4 cell count, integrase inhibitor resistance 
and Overall Susceptibility Score (OSS)* for study TMB-301  

 No. of subjects achieving  
<50 HIV-1 RNA copies/mL 

(n/N)  

No. of subjects achieving 
<200 HIV-1 RNA copies/mL  

(n/N) 
Virologic response  17/40 (43%) 20/40 (50%) 
CD4 cell counts (cells/ mm3) 

< 50  
50-200  
> 200  

 
3/17 (18%) 
6/10 (60%) 
8/13 (62%) 

 
4/17 (24%) 
7/10 (70%) 
9/13 (69%) 

HIV-RNA (copies/mL) 
< 100 000  
≥ 100 000  

 
16/33 (48%) 
1/7 (14%) 

 
19/33 (58%) 
1/7 (14%) 

Resistance 
With INSTI resistance  
Without INSTI resistance  

 
11/27 (41%) 
6/13 (46%) 

 
12/27 (44%) 
8/13 (62%) 

OSS 
0  
1  
2  
3  
4  

 
1/5 (20%) 
5/12 (42%) 
9/18 (50%) 
1/3 (33%) 
1/2 (50%) 

 
1/5 (20%) 
6/12 (50%) 

11/18 (61%) 
1/3 (33%) 
1/2 (50%) 

* The OSS indicates the number of fully active drugs in a subject’s Optimized Background Regimen (OBR) based on both 
current and available historical resistance test results. Demonstrating drug susceptibility by both genotypic and phenotypic 
testing was required, when testing by both methods was technically feasible. As an example, an OSS of 2 would indicate 
that the HIV-1 isolate tested was fully susceptible to two drugs in the OBR. 

 
Trial TNX-355.03 
Study TNX-355.03 was a multicenter, randomized, double-blinded, placebo-controlled, multi-dose, 3-
arm safety and efficacy study in 82 subjects with HIV-1 and who were failing or had failed highly 
active antiretroviral therapy. Subjects all received OBR plus 1 of the following regimens: alternating 
intravenous (IV) infusions of 15 mg/kg ibalizumab and placebo, weekly for the first 9 doses (through 
the Week 8 visit), then IV infusions of 15 mg/kg ibalizumab every 2 weeks (Arm A); 10 mg/kg 
ibalizumab IV infusions weekly for the first 9 doses (through the Week 8 visit), then IV infusions of 
10 mg/kg ibalizumab every 2 weeks (Arm B); or weekly placebo IV infusions for the first 9 doses 
(through the Week 8 visit), then IV infusions of placebo every 2 weeks (Placebo arm). Patients in all 
three arms also received an OBR. As of Week 16, patients in Placebo arm who experienced virologic 
failure had the option of receiving 15 mg/kg open-label ibalizumab every 2 weeks and/or switching to 
a new OBR. Patients in Arm A and B arm who experienced virologic failure had the option of 
switching to a new OBR. 
 
At Week 2, the mean viral load decrease was 0.87 log10 copies/mL in Arm A, 1.15 log10 copies/mL in 
Arm B and 0.38 log10 copies/mL in the Placebo arm (p=0.003 vs Arm A, p<0.001 vs Arm B). 
 
By Week 16, i.e. prior to the possible switching of patients in the Placebo arm to the 15 mg/kg dose of 
ibalizumab every 2 weeks and/or to change in OBR for all patients, mean viral load decrease was 1.07 
log10 copies/mL in Arm A, 1.33 log10 copies/mL in Arm B and 0.26 log10 copies/mL in the Placebo 
arm  (p=0.002 vs Arm A, p<0.001 vs Arm B). 
 



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Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Trogarzo in one or more subsets of the paediatric population in the treatment of HIV-1 infection (see 
section 4.2 for information on paediatric use). 
  
5.2 Pharmacokinetic properties 
 
Absorption 

Following the recommended dose regimen (a single loading dose of 2,000 mg followed by a 
maintenance dose of 800 mg every 2 weeks), ibalizumab concentrations reached steady-state levels 
after the first 800 mg maintenance dose with mean trough concentrations over 30 µg/mL throughout 
the dosing interval.  The median time to maximum serum concentration (Tmax) of 2,000 mg and 
800 mg is 1 hr and 10 min, respectively. Ibalizumab is administered as an IV infusion. The 
bioavailability is 100% by definition.   
 
Distribution 

The volume of distribution of ibalizumab is approximately 4.8 L, which is comparable with vascular 
space, based on the performed population pharmacokinetics analysis.  

Biotransformation 

Specific metabolism studies were not conducted because ibalizumab is a protein. Ibalizumab is 
expected to degrade to small peptides and individual amino acids. 
 
Elimination 

Following single-dose administrations of 10 and 25 mg/kg of ibalizumab, clearance is 0.5 to 
0.36 mL/h/kg and elimination half-life is 37.8 and 64.1 hours, respectively. The elimination is 
nonlinear and concentration-dependent. 

Linearity/non-linearity 

Ibalizumab administered as a single agent exhibits nonlinear pharmacokinetics at a dose range of 
0.3-25 mg/kg. Following administration of ibalizumab, at the clinically relevant dose rage of 
800-2,000 mg, the maximum serum concentration (Cmax) increased dose proportionally, whereas the 
area under the concentration-time curve (AUC) increased in a greater than dose-proportional manner. 
Such non-linear effects in clearance are common for monoclonal antibodies targeting cell surface 
molecules, such as CD4. This behaviour is characteristic of saturable (capacity-limited) elimination 
kinetics. 

Special populations 

A population pharmacokinetic analysis was performed to explore the potential effects of selected 
covariates (age, body weight, sex, baseline CD4+ cell count) on ibalizumab pharmacokinetics. The 
results suggest that ibalizumab concentration decreases as body weight increases. The body weight 
range was very narrow in the population PK model, and the impact of body weight may not be 
precisely estimated. However, the effect is unlikely to impact virologic outcome and does not warrant 
a dose adjustment. 



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Renal impairment 

No formal studies were conducted to examine the effects of renal impairment on the pharmacokinetics 
of ibalizumab. Renal impairment is not anticipated to impact the pharmacokinetics of ibalizumab.  

Hepatic impairment 

No formal studies were conducted to examine the effects of hepatic impairment on the 
pharmacokinetics of ibalizumab. Hepatic impairment is not anticipated to impact the pharmacokinetics 
of ibalizumab.  

Paediatric population  

Ibalizumab pharmacokinetics have not been evaluated in paediatric patients. 
 
Elderly population  

Ibalizumab pharmacokinetics in geriatric patients (≥ 65 years of age) is limited (n = 5). Results are 
similar to the adult population (≥18 to 65 years of age), however no definite conclusions can be drawn. 
 

5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of in vitro and in 
vivo safety assessments. 
 
Toxicity to reproduction and development 

A pre- and post-natal developmental study was performed in cynomolgus monkeys. Ibalizumab was 
administered to pregnant females at a 110mg/kg weekly dose from gestation Day 20-22 until 
parturition (approximately 22 doses/animal). This dose was administered as it is at least 10-fold the 
estimated free clinical AUC and Cmax for the 800 mg Q2W dose. Ibalizumab was generally well 
tolerated in pregnant monkeys and in their offspring, when evaluated through 180 ± 2 days post-
partum. There were no ibalizumab-related adverse effects (maternal, foetal, or infant) at 110 mg/kg 
(No-Observed-Adverse-Effect Level, NOAEL). However, CD4+ cells in infants of treated females 
were temporarily suppressed from BD14-91 compared to control, but there was no further impact on 
immunocompetence of the infants. The relevance of this effect for human pregnancy and lactation 
remains unknown. Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) 
for developmental effects was 110 mg/kg.  
 
Genotoxicity, carcinogenic potential 

Genotoxicity and carcinogenicity studies have not been conducted. 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sucrose 
Sodium chloride 
Polysorbate 80 
Histidine 
Hydrochloric acid (for pH-adjustment) 
Water for injections 
 



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6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products except those mentioned in section 6.6.  
 
6.3 Shelf life 
 
Unopened vial 

4 years 
 
Diluted solution 

If not administered immediately, store the diluted ibalizumab solution below 25°C for up to 4 hours, or 
in a refrigerator (2°C to 8°C) for up to 24 hours. If refrigerated, allow the diluted ibalizumab solution 
to stand at room temperature (20°C to 25°C) for at least 30 minutes but no more than 4 hours prior to 
administration.  
 
6.4 Special precautions for storage 
 
Store and transport refrigerated (2°C to 8°C). 
 
Do not freeze.  
 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
2 mL vial (Type I borosilicate glass) sealed with a stopper (butyl rubber) and an aluminum crimp cap. 
 
Pack of 2 vials. 
 
6.6 Special precautions for disposal and other handling 
 
This medicinal product should be inspected visually for particulate matter and discoloration prior to 
administration. Vials containing non-diluted ibalizumab or infusion bag containing diluted ibalizumab 
must be discarded if solution is cloudy, if there is pronounced discoloration or if there is foreign 
particulate matter. 

Ibalizumab is administered intravenously (IV), after diluting the appropriate number of vials in 
250 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. See Table 4 below for the 
appropriate number of vials required to prepare both the loading dose of 2,000 mg and the 
maintenance doses of 800 mg.  

Table 4. Recommended ibalizumab dose and number of vials per administration 

Ibalizumab dose Ibalizumab vials  
(Total volume to be withdrawn)  

Loading dose of 2,000 mg 10 vials (13.3 mL)  
Maintenance dose of 800 mg  4 vials (5.32 mL)  

 
Ibalizumab concentrate for solution for infusion should be prepared by a healthcare professional using 
aseptic technique as follows:  

• Remove the flip-off cap from the vial and wipe with an alcohol swab.  



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• Insert sterile syringe needle into the vial through the center of the stopper and withdraw 
1.33 mL from each vial (NOTE: a small residual amount may remain in the vial, discard 
unused portion) and transfer into a 250 mL intravenous bag of sodium chloride 9 mg/mL 
(0.9%) solution for injection. Other intravenous diluents must not be used to prepare the 
ibalizumab solution for infusion.  

• Once diluted, the ibalizumab solution should be administered immediately. 
• Discard partially used vials or empty vials of ibalizumab and any unused portion of the diluted 

ibalizumab solution in accordance with local requirements.  

7. MARKETING AUTHORISATION HOLDER 
 
Theratechnologies Europe Limited 
4th Floor, 2 Hume Street, Dublin 2, D02 DV24, Ireland 
Tel: 00800 08250830 
Tel.: +49 (0) 30 3119 6151 
medinfo.eu@theratech.com 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1359/001 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 September 2019 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


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ANNEX II 

 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 



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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer of the biological active substance 

WuXi Biologics Co, Ltd 
108 Meiliang Road,  
MaShan Binhu District,  
Wuxi, 214092,  
China 

 

Name and address of the manufacturer responsible for batch release 

MIAS Pharma Limited 
Suite 2 Stafford House, Strand Road, 
Portmarnock, Co. Dublin, D13 H525 
Ireland 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription.(see Annex I: Summary of Product 
Characteristics, section 4.2). 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

 

• Periodic safety update reports  
 

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 

The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation. 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the  
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed  subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 



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as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 

• Obligation to conduct post-authorisation measures 
 

The MAH shall complete, within the stated timeframe, the below measures: 

 
Description Due date 

Post-authorisation efficacy study (PAES): 
 
In order to further characterise the efficacy of ibalizumab in combination with other 
anti-retroviral medicinal products, for the treatment of adults infected with multidrug 
resistant HIV-1 infection for whom it is otherwise not possible to construct a 
suppressive antiviral regimen, the MAH should conduct and submit the results of a 
study based on data from a product registry. This study should be conducted according 
to an agreed protocol. 
  

 
Final report 
submission: 31-
Oct-2025 

 



16 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



18 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON (Contains 2 vials of 200 mg) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trogarzo 200 mg concentrate for solution for infusion 
ibalizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 200 mg of ibalizumab  
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose 
Sodium chloride 
Polysorbate 80 
Histidine 
Hydrochloric acid 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion. 
2 vials 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use. 
Single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



19 

9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated. 
Do not freeze.  
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Theratechnologies Europe Limited 
4th Floor, 2 Hume Street,  
Dublin 2, D02 DV24 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1359/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



20 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Trogarzo 200 mg sterile concentrate 
ibalizumab 
IV  
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
200 mg 
 
 
6. OTHER 
 
 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



22 

Package leaflet: Information for the patient 
 

Trogarzo 200 mg concentrate for solution for infusion 
ibalizumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Trogarzo is and what it is used for  
2. What you need to know before you use Trogarzo 
3. How to receive Trogarzo 
4. Possible side effects  
5. How to store Trogarzo 
6. Contents of the pack and other information 
 
 
1. What Trogarzo is and what it is used for 
 
What Trogarzo is 
Trogarzo contains the active substance ibalizumab. This is a type of protein called a ‘monoclonal 
antibody’ that can attach to a specific target in the body. It belongs to a group of medicines called 
‘antiretrovirals’. 
 
What Trogarzo is used for 
Trogarzo is used in adults to treat HIV infection that has not responded to a number of HIV treatments 
in the past. 
 
Your doctor has prescribed Trogarzo to help control your HIV infection. 
 
Trogarzo is used in combination with other medicines.  
It will be used together with other HIV medicines called ‘antiretrovirals’.  
 
How Trogarzo works 
The HIV virus infects cells in your blood called ‘CD4’ or ‘T-cells’. Trogarzo attaches to the CD4 
receptor and blocks HIV from entering and infecting your blood cells. This will reduce the amount of 
virus in your body, and keeps it at a low level. This helps your body to increase the CD4 cell count in 
your blood. CD4 cells are a type of white blood cell that are important in helping your body to fight 
infection. 
 
2. What you need to know before you use Trogarzo  
 
You must not be given Trogarzo: 
- if you are allergic to ibalizumab or any of the other ingredients of this medicine (listed in section 

6).  
If you are not sure, talk to your doctor or nurse before being given Trogarzo. 
 



23 

Warnings and precautions  
 
Look out for side effects 
Trogarzo can cause serious side effects that you need to tell your doctor or nurse about straight away. 
These include: 
• signs of a new infection (called ‘immune reconstitution inflammatory syndrome’)   
Tell your doctor or nurse straight away if you get any of the above (for more information see ‘Serious 
side effects’ in section 4).  
 
Passing HIV to others 
This medicine reduces the amount of HIV in your body. When this is stably kept at undetectable 
levels, the chances that you can still pass on HIV to your sexual partners become negligible. You can 
still pass on HIV when taking this medicine, if you have detectable levels of HIV in your body. Talk to 
your doctor or nurse about how to avoid infecting other people. 
 
Children and adolescents 
Do not give this medicine to children and adolescents below 18 years of age. This is because Trogarzo 
has not been studied in this age group. 
 
Other medicines and Trogarzo 
Tell your doctor if you are taking, have recently taken or might take any other medicines.  
 
Pregnancy 
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice before taking this medicine. 
 
If you could get pregnant while taking Trogarzo, you need to use a reliable method of barrier 
contraception (for example, a condom) with other methods of contraception including oral 
contraceptive (the pill) or other hormonal contraceptives (for example, implants or injections), to 
prevent pregnancy. 
 
Breast-feeding 
Women who are HIV-positive must not breast feed because HIV infection can be passed on to the 
baby in breast milk. It is unknown if Trogarzo can pass into breast milk. 
If you are breast-feeding, or thinking about breast-feeding: 
 → Talk to your doctor immediately.  
 
Driving and using machines 
Do not drive or use machines after you have been given Trogarzo if you do not feel well enough. 
Headache, feeling dizzy, feeling sick (nausea) or feeling tired are common side effects of Trogarzo and 
can affect your ability to drive or use machines. 
  
Trogarzo has a low sodium content 
Trogarzo contains less than 1 mmol sodium (23 mg) in each dose and therefore is essentially 
sodium-free. 
 
 
3. How to receive Trogarzo 
 
You will be given Trogarzo under the supervision of an experienced doctor or nurse.  
 
Trogarzo is used in combination with other medicines called ‘antiretrovirals’. 
 
How much Trogarzo you will be given 
The recommended dose of Trogarzo is: 
• a single dose of 2,000 mg on the first occasion 
• followed by a maintenance dose of 800 mg every 2 weeks.  



24 

Trogarzo will be added to a drip (infusion bag) containing a sodium chloride (saline) solution before 
use.  

More than one vial of Trogarzo will be needed to get the required dose. 

 
How you will be given Trogarzo 
The drip (infusion) will be given into a vein over 15 to 30 minutes. Your doctor or nurse will monitor 
you during the Trogarzo infusion and for a period of time after your infusion.  
 
If you miss a dose of Trogarzo 
• It is very important that you are given Trogarzo every 2 weeks as instructed by your doctor.  
• Do not change the schedule of your Trogarzo infusions or any of your other antiretroviral 

medicines without talking to your doctor first.  
• If you miss an appointment, ask your doctor straight away when to schedule your next dose. 
 
If you stop having Trogarzo 
Keep having Trogarzo infusions until your doctor tells you to stop. If you stop and there is a gap in 
your treatment, the level of HIV virus in your blood may begin to rise. This is less likely if you receive 
Trogarzo regularly and without gaps in treatment. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
Talk to your doctor or nurse straight away if you get any of the following serious side effects: 
• Signs of a new infection, changes in your immune system, can happen when you start using 

HIV medicines. Your immune system might get stronger and begin to fight infections that have 
been hidden in your body for a long time (this is called ‘immune reconstitution inflammatory 
syndrome’). Look out for new signs of infection after receiving Trogarzo; these can be different 
from person to person depending on the type of infection that was hidden and might include fever, 
headache, difficulty breathing, stomach ache, coughing and swollen glands (lumps and bumps on 
your body, neck, armpit or groin).  

• Allergic reaction (hypersensitivity). 
 
Other side effects 
Tell your doctor or nurse if you notice any of the following side effects: 

Common (may affect up to 1 in 10 people): 

• skin rash 

• diarrhoea  
• feeling sick (nausea) or being sick (vomiting) 

• dizziness 

• headache 

• feeling tired  

• dry skin  

• dermatitis – a type of eczema with dry itchy skin  

• pain and feeling numb in hands, feet or legs 
 



25 

Uncommon (may affect up to 1 in 100 people): 

• tremor 

• feeling dizzy, faint or light headed when standing up  

• dry mouth  

• feeling hot 

• spots or swelling  

• itchy skin, or skin damage  
• bruising  

• abnormal heartbeat 

• high blood pressure or frequent changes in blood pressure  
 
Seen in tests: 

• abnormal results on tests of the heart’s electrical activity (electrocardiogram) 

 
Tell your doctor or nurse if you notice any of the side effects listed above. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Trogarzo 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). 
 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
6. Contents of the pack and other information 
 
What Trogarzo contains  
- The active substance is ibalizumab. 
- One vial contains 200 mg of ibalizumab in 1.33 mL of solution. 
- The other excipients are sucrose, sodium chloride (see section 2 ‘Trogarzo has a low sodium 

content’), polysorbate 80, histidine, hydrochloric acid, water for injections.  
 
What Trogarzo looks like and contents of the pack 
Trogarzo is a colourless to slightly yellow, clear to slightly opalescent concentrate for solution for 
infusion (sterile concentrate), with no visible particles. 
 
The pack size is 2 glass vials per carton. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


26 

Marketing Authorisation Holder and manufacturer 
Theratechnologies Europe Limited 
4th Floor, 2 Hume Street,  
Dublin 2, D02 DV24, Ireland 
Tel: 00800 08250830 
Tel.: +49 (0) 30 3119 6151 
medinfo.eu@theratech.com 
 
  
This leaflet was last revised in month YYYY. 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
Method of administration  
 
Intravenous use 

Diluted ibalizumab solution should be administered by a healthcare professional. 

Ibalizumab should be administered as an intravenous infusion. Ibalizumab should not be administered 
as an intravenous push or bolus. 

The duration of the first infusion (loading dose) should be no less than 30 minutes. If no infusion-
associated adverse reactions have occurred, the duration of the subsequent infusions (maintenance 
doses) can be decreased to no less than 15 minutes. 

After the infusion is complete, flush with 30 mL of sodium chloride 9 mg/mL (0.9%) solution for 
injection.  

All patients must be observed during and for 1 hour after completion of ibalizumab administration for 
at least the first infusion. If a reaction occurs, the infusion should be discontinued and appropriate 
medical therapies should be administered. Prophylactic medication is not warranted prior to each 
infusion. If the patient does not experience an infusion-associated adverse reaction, the post-infusion 
observation time can be reduced to 15 minutes thereafter. 

Instructions on dilution of ibalizumab before use 
 
Ibalizumab is administered intravenously (IV), after diluting the appropriate number of vials in 
250 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. See the table below for the 
appropriate number of vials required to prepare both the loading dose of 2,000 mg and the 
maintenance doses of 800 mg.  

         Recommended ibalizumab dose and number of vials per administration 
Ibalizumab dose Ibalizumab vials  

(total volume to be withdrawn)  
Loading dose of 2,000 mg 10 vials (13.3 mL)  
Maintenance dose of 800 mg  4 vials (5.32 mL)  

 
Ibalizumab concentrate for solution for infusion should be prepared by a healthcare professional using 
aseptic technique as follows:  

• Remove the flip-off cap from the vial and wipe with an alcohol swab.  



27 

• Insert sterile syringe needle into the vial through the center of the stopper and withdraw 
1.33 mL from each vial (NOTE: a small residual amount may remain in the vial, discard 
unused portion) and transfer into a 250 mL intravenous bag of sodium chloride 9 mg/mL 
(0.9%) solution for injection. Other intravenous diluents must not be used to prepare the 
ibalizumab solution for infusion.  

• Once diluted, the ibalizumab solution should be administered immediately. 
• Discard partially used vials or empty vials of ibalizumab and any unused portion of the diluted 

ibalizumab solution in accordance with local requirements. 

Precautions to be taken before handling or administering the medicinal product 
 
This medicinal product should be inspected visually for particulate matter and discoloration prior to 
administration. Vials containing non-diluted ibalizumab or infusion bag containing diluted ibalizumab 
must be discarded if solution is cloudy, if there is pronounced discoloration or if there is foreign 
particulate matter. 


	ANNEX I
	SUMMARY OF PRODUCT CHARACTERISTICS
	ANNEX II
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	ANNEX III
	LABELLING AND PACKAGE LEAFLET
	A. LABELLING
	B. PACKAGE LEAFLET