A Phase 1 Study to Assess the Immunogenicity of QL0605 Compared to US Neulasta in Healthy Subjects

Inclusion Criteria:

1. Subjects must give written informed consent before any assessment is performed;
2. Subjects must be a healthy male or female aged 18 to 55 years (both inclusive) at thetime of informed consent;
3. Body weight ≥60 kg (males) or ≥50 kg (females) at the Screening Visit;
4. The Body Mass Index (BMI) between 18.5 to 29.9 kg/m2 (inclusive) at the ScreeningVisit (BMI = Body weight (kg)/[Height (m)]2);
5. Absolute neutrophil count and total leukocyte count are within the normal laboratoryreference ranges; platelet count, hematocrit, and haemoglobin results are not belowthe lower limit of laboratory reference ranges; reticulocyte count is not above theupper limit of laboratory reference ranges; all other laboratory parameters withinreference ranges or showing no clinically relevant deviations as judged by theInvestigator. If the results of the laboratory parameters (other than total leukocytecount, platelet count, neutrophil count, hematocrit, reticulocyte count andhemoglobin) are outside the normal reference ranges, the subject may be included onlyif the Investigator judges the abnormalities or deviations from normal to be notclinically significant or to be appropriate for the population under study;
6. Female subjects must either be:

• of non-childbearing potential:
• Postmenopausal (defined as at least 1 year without any menses) prior to theScreening Visit, and the follicle stimulating hormone levels indicative ofmenopause according to local laboratory reference ranges at Screening, or
• Documented permanent surgically sterile (hysterectomy, bilateralsalpingectomy and bilateral oophorectomy) since at least 6 weeks before theScreening Visit
• or, if of childbearing potential:
• Agree not to try to become pregnant during the clinical study and for 49days after the last IMP administration and
• Must have a negative serum pregnancy test at screening and
• If heterosexually active, agree to consistently use 2 forms of birth control (1 of which is a highly effective method† and 1 must be a barrier method‡)from screening and throughout the study period, and for 49 days after lastIMP administration. The highly effective method of contraception should bestable for at least 28 days prior to first IMP administration.
• Highly effective forms of birth control include (i.e., less than 1%failure rate per year when used consistently and correctly):
• Consistent and correct usage of established oral contraception (this isconsidered highly effective, because it is used in combination with a barriermethod)
• Injected or implanted hormonal methods of contraception
• Established (with a failure rate < 1%) intrauterine device (IUD) or intrauterinesystem (IUS)
• Bilateral tubal ligation
• Any male partner that has undergone effective surgical sterilization, providedthat the partner is the sole sexual partner of the female study participant
• Sexual abstinence is considered a highly effective method only if defined asrefraining from heterosexual intercourse during the entire period of riskassociated with the study treatments and complies with the preferred and usuallifestyle of the subject. ‡ Barrier methods of birth control include for males and females:
• Condom without spermicidal foam/gel/film/cream/suppository or fat- or oilcontaining lubricant.
• Occlusive cap (diaphragm or cervical/vault caps) with spermicidalfoam/gel/film/cream/suppository.

7. Female subjects must agree not to breastfeed starting at the Screening Visit andthroughout the clinical study period, and for 49 days after last IMP administration;
8. Female subjects must not donate ova starting at the Screening Visit and throughout theclinical study period, until the final Follow-up Visit;
9. Male subjects and their female spouse/partners who are of childbearing potential mustbe using 2 forms of birth control (1 of which is a highly effective method† and 1 mustbe a barrier method‡) starting at the Screening Visit and throughout the study periodand for 49 days after the last IMP administration. A condom is required to be usedalso by vasectomized men to prevent delivery of the drug via seminal fluid;
10. Subjects must be non-smoker, or light smokers who smoke not more than 5 cigarettes or 1 cigar or 1 pipe per day and who agree to abstain from smoking while resident at theclinical unit.

Exclusion Criteria:

1. Known previous exposure to filgrastim, pegfilgrastim, granulocyte colony stimulatingfactor (G-CSF) or any analogue of these;
2. Positive test results for anti-PEG-GCSF-antibodies at the Screening Visit or based onhistorical data (not older than 3 months);
3. Known hypersensitivity to the study drug or any of its constituents (e.g., fructoseintolerance), hypersensitivity to Escherichia coli derived proteins;
4. History of an acute severe allergic reaction (e.g., anaphylaxis; delayedhypersensitivity reaction); concurrent or history of moderate to severe allergyrequiring medical treatment (including moderate seasonal allergies); concurrent orhistory of clinically significant latex allergy;
5. Current evidence of atopic eczema or allergic bronchial asthma;
6. History or current evidence of any clinically significant condition that mightinterfere with the distribution, metabolism or excretion of the any of theinvestigational drugs;
7. Concurrent or history of cardiac, hepatic, renal, gastrointestinal, respiratory,neurological, central nervous, mental disorders and/or hematological functiondisorders, which, in the judgment of the Investigator or any of the Sub-Investigators,may affect participation in this clinical study;
8. Clinically significant vital sign abnormalities or systolic blood pressure [BP] < 90or > 139 mmHg, diastolic BP < 50 or > 89 mmHg, and/or pulse < 50 or > 90 beats perminute [bpm] at the Screening Visit (mean of triplicate measurements);
9. Subjects with abnormal 12-lead Electrocardiograms (ECGs) (QTcF >450 ms in males and 470 ms in females, signs of ischemia, sinus tachycardia [heart rate, HR >90] or sinusbradycardia [HR <50], ventricular conduct delay [QRS >120 ms] or others) which, in thejudgment of the Investigator or any of the Sub-investigators, may be clinicallyrelevant;
10. Renal impairment with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2,based on creatinine clearance calculation by Chronic Kidney Disease EpidemiologyCollaboration (CKD-EPI) formula.
11. Any clinically relevant laboratory findings that, in the opinion of the Investigator,would preclude inclusion in the trial; including alanine aminotransferase (ALT),aspartate aminotransferase (AST), and bilirubin (total) > upper limit of normal (ULN).If any of these tests are out-of-range, the tests can be repeated once;
12. Previous or concurrent malignancy;
13. First degree relatives with hematological malignancy;
14. Clinically significant active infection within 4 weeks before IMP administration;
15. Any past or concurrent medical conditions that potentially increase the subject'srisks or affect the evaluation of any study results, like medical history withevidence of clinically relevant pathology e.g., sickle cell disorders, spleenpathologies, hematologic malignancies or myelodysplastic disorders, and pulmonaryillnesses such as Acute Respiratory Distress Syndrome, interstitial pneumonia,pulmonary edema, pulmonary infiltrates and pulmonary fibrosis;
16. Subject exhibiting spleen enlargement (as determined by ultrasound assessment) orother relevant abnormality which is, at the discretion of the Investigator, acontraindication for treatment with pegfilgrastim;
17. Presence of any clinically significant finding that, in the opinion of theInvestigator, would preclude continuation in the study;
18. Participation (last dosing) in a previous clinical trial with an experimental drugwithin 3 months before the first administration of the IMP or five half lives of thedrug, whichever is longer, prior to dosing;
19. Use of depot injectable solutions within 6 months before IMP administration. Hormonaldepot injections for contraception or hormonal replacement therapy are allowed;
20. Intake of drugs and/or drugs with a long half-life within 4 weeks before IMPadministration;
21. Positive test results for hepatitis B surface antigen (HbsAg), anti hepatitis B core (anti-HBc) antibodies indicative of active hepatitis, hepatitis A virus antibodies (immunoglobulin M [IgM]), hepatitis C virus (HCV) antibodies or human immunodeficiencyvirus (HIV) type-1 and/or type-2 antibodies at the Screening Visit;
22. Has a history of chronic drug or alcohol abuse in the last 5 years before the date ofadministration of the IMP and/or positive urine drugs of abuse tests (phencyclidines,benzodiazepines, cocaine, amphetamines/ methamphetamines, cannabinoids, opiates,barbiturates, and tricyclic antidepressant drugs) and / or positive alcohol urine testat screening and admission;
23. Subjects who regularly consume large quantities of alcohol.

• For Berlin unit: drinking > 168 g (males) and > 84 g (females) pure alcohol perweek (10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 125 mLof wine [10%]) within 3 months prior to admission to the clinical unit;
• For London unit: drinking > 21 units (males) and > 14 units (females) of alcoholper week (beer 5%, 259 ml = 10.36 g , wine 10% 100 ml = 8 g and Spirits 40% 35 ml = 11.20 g);

24. Not willing to abstain from xanthine-containing products from 24 hours prior to theScreening Visit and prior to the admission visit [Day -1] and during the in-housestay, and at all other times, to limit the consumption of caffeinated beverages orxanthine-containing products to no more than 6 units per day (1 unit = 120 mg ofcaffeine);
25. Plasma donation within 1 month before the Screening Visit or any blood donation /blood loss > 500 mL during the 3 months before the Screening Visit, or any plannedblood donation during the time the subject is on study;
26. Use of any prescription drug (excluding hormonal contraceptives, hormone replacementtherapy, and topical medications used for local treatment) or any over-the-counterdrug (except ibuprofen and paracetamol) within the 2 weeks (or less than 5 x thehalf-life of that medication, whichever is longer) before the Baseline Visit in Period 1, which, in the judgment of the Investigator or Sub-Investigators, may affectparticipation in this clinical study; vitamins, minerals and nutritional supplementsmay be taken at the discretion of the Investigator;
27. Subjects being on a special diet or with significant weight loss from a weightreduction diet (e.g. more than approx. 5 kg within 1 month) before the Screening Visitor unwilling to maintain the same weight for the duration of the study;
28. Not willing to avoid poppy seeds and foods containing them for 72 hours prior toScreening and Day -1 visits;
29. A current (suspected or confirmed) pregnancy or currently nursing (women only);
30. Vulnerable subjects (i.e., persons under any administrative or legal supervision orpersons kept in detention);
31. Subjects who are employees of Sponsor, clinical research organization (CRO) or who isthe Investigator or any sub-Investigator, research assistant, pharmacist, studycoordinator, other site staff or relative thereof directly involved in the conduct ofthe clinical study;
32. Subjects who are not able to read, speak and understand the German language (Berlinunit) or the English language (London unit);
33. Any psychological or emotional problems/disorders or resultant therapy that is likelyto invalidate informed consent, or limit the ability of the subject to comply with theprotocol requirements.
34. Subject has a positive PCR test result for SARS-CoV-2 before randomization.
35. Subject has clinical signs and symptoms consistent with COVID-19, e.g., fever, drycough, dyspnea, sore throat, fatigue or confirmed current infection by appropriatelaboratory test within the last 4 weeks prior to or at screening or on admission.
36. Subject who had severe course of COVID-19 (extracorporeal membrane oxygenation [ECMO],mechanically ventilated).