PK, PD, Safety, and Efficacy Study of Gefurulimab in Pediatric Patients with AChR+ Generalized Myasthenia Gravis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

22 Dec 2025 → ongoing

Decision date (initial)

2025-03-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Pharmacodynamic

To characterize the PK and PD of treatment with gefurulimab in pediatric participants with AChR+ gMG

Secondary objectives 2

1. "To evaluate safety of gefurulimab in pediatric participants with AChR+ gMG"
2. To assess the efficacy of gefurulimab in pediatric participants with AChR+ gMG

Conditions and MedDRA coding

Generalized Myasthenia Gravis with autoantibodies against acetylcholine receptor (AChR)

Study design 3 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003302-PIP01-22

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Participant must be 6 to < 18 years of age at the time of signing the informed consent/assent.
2. "Participants who have a documented diagnosis of gMG ≥ 3 months (90 days) prior to Screening based on clinical disease features and at least 1 of the following confirmatory tests. Test results may be collected from participant records or obtained during Screening: • Positive response in an acetylcholinesterase inhibitor test, for example, the edrophonium chloride test • Abnormal neuromuscular transmission demonstrated by repetitive nerve stimulation or single fiber electromyography • Previous improvement of symptoms or signs related to gMG during treatment with on oral acetylcholinesterase inhibitor, as confirmed by the treating physician"
3. Positive serological test for AChR autoantibodies (previous test results, if applicable, must be confirmed at Screening by central laboratory).
4. MGFA Class II to IV at Screening and on Day 1.
5. "Must have QMG total score as outlined below: • Participants 12 to < 18 years of age must have QMG total score ≥ 12 at Screening and on Day 1 • Participants 6 to < 12 years of age will have no minimum QMG total score required for inclusion; however, participants must have documented limb weakness in at least 1 limb"
6. "Participants receiving treatment with any of the following medications must be on a stable dose for the time periods specified in Table 11 at their Screening Visit: NOTE: If a participant has recently discontinued any of the above medications, a period of time equal to the stable dose requirement listed above for that medication (eg, ≥ 2 months for azathioprine or ≥ 4 weeks for corticosteroids) must have passed prior to the first day of the Screening Period. Rescue therapy including PP, PE, IVIg, SCIg, or high-dose corticosteroids for a participant experiencing a deterioration of gMG symptoms or signs, eg, in a myasthenic crisis, during Screening is not a reason for exclusion. However, participants requiring rescue therapy during Screening may be eligible after ≥ 4 weeks have passed since completion of the rescue therapy. Participants rescreened outside the Screening window are required to sign a new ICF/assent (Section 10.1.3)."
7. "Body weight ≥ 20 kg and in the opinion of the Investigator, likely to remain above this minimum weight for the duration of the study. NOTE: Dosage regimen for the ≥ 20 to < 40 kg weight group will be confirmed after modelling and simulations are updated with adult PK/PD data from Study ALXN1720-MG-301."
8. Participants of childbearing potential must follow protocol-specified contraception guidance as outlined in Section 10.6.
9. The Investigator, or a person designated by the Investigator, will obtain written informed consent from each study participant’s legal guardian (as defined in Section 10.1.3) and the participant’s assent, when applicable, before any study-specific activity is performed. All legal guardians should be fully informed, and participants should be informed to the fullest extent possible, about the study in language and terms they are able to understand.
10. All participants must receive vaccinations for S pneumoniae and Hib, prior to Day 1, unless previously vaccinated according to current national/local vaccination guidelines.
11. To reduce the risk of meningococcal infection (N meningitidis), all participants must be vaccinated against meningococcal infection from serogroups A, C, W, Y (and B where available) within 3 years prior to study intervention on Day 1. If vaccination occurs < 2 weeks prior to Day 1, the participants will receive prophylactic antibiotics for at least 2 weeks after initial meningococcal vaccination for serogroups A,C,W,Y (and B, where available).
12. A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow up; accompany the participant to the study site on each assessment day according to the SoA (eg, able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the rating scales during the scheduled study visits; accurately and reliably dispense study intervention as directed.
13. A legal guardian or primary caregiver must be able to accurately maintain the child’s take-home record, including items of general health.

Exclusion criteria 21

1. "Clinical features that, in the opinion of the Investigator, are consistent with a Clinical Deterioration, as defined in Section 4.1.6.1 including myasthenic crisis, ≤ 28 days prior to Screening or during the Screening Period. NOTE: Participants may be eligible for rescreening once the Clinical Deterioration has resolved, and standard of care treatment has been resumed and stable for the periods of time described in inclusion criteria (Table 11)."
2. Any medical condition (eg, cardiac, pulmonary, renal, oncologic, neurological or psychiatric disorder) or risk factor that, in the opinion of the Investigator or the Medical Monitor, might interfere with participation in the study, pose any added risk to the participant, or confound the assessment of safety or efficacy of the study intervention.
3. History of thymectomy or any other thymic surgery within 6 months prior to screening
4. "Any untreated thymic malignancy, carcinoma, or thymoma. NOTE: Participants with a history of treated malignant thymoma or carcinoma are eligible if they meet all of the following conditions: a. Treatment completed > 5 years prior to the Screening Visit b. No recurrence within the 5 years prior to the Screening Visit c. No radiological indication of recurrence in a CT with contrast or MRI scan, including administration of IV contrast, performed within 6 months of Day 1 NOTE: Participants with a history of treated benign thymoma are eligible if they meet all of the following conditions: a. Histopathological or equivalent records confirming the diagnosis of benign thymoma b. Treatment completed > 6 months prior to the Screening Visit c. No known recurrence within the 6 months prior to the Screening Visit d. No radiological indication of recurrence in a CT or MRI scan, including administration of IV contrast, performed within 6 months of Day 1 e. If adequate records confirming the diagnosis of benign thymoma are not available, the participant must satisfy the eligibility criteria for thymic malignancy or carcinoma stated above. NOTE: Thymomas classified as ≤ Stage II, according to the Masaoka Staging System are considered benign; thymomas classified as ≥ Stage III are considered malignant."
5. History of or unresolved N meningitidis infection
6. History of persistent or recurrent infections in the past 12 months that might pose an additional risk for the participant.
7. Active systemic bacterial, viral, or fungal infection ≤ 14 days prior to Day 1.
8. History of hypersensitivity to any ingredient contained in the study intervention, including its device components (see Table 12).
9. "History of malignancy within 5 years of screening NOTE: The only exceptions not requiring exclusion from the study are skin cancer other than melanoma and cervix carcinoma in situ that has been treated with no evidence of recurrence."
10. Known or suspected history of alcohol or substance use disorder, based on current diagnostic criteria provided in the Diagnostic and Statistical Manual of Mental Disorders, within 12 months prior to Screening.
11. "Concomitant treatment with any of the following medications, or prior treatment for the time periods specified below is not permitted: • Complement inhibitor: Received within < 5 half-lives before enrollment on Day 1. Participants receiving prior treatment with a complement inhibitor ≥ 5 half-lives before enrollment on Day 1 may be enrolled but must have tolerated such treatment well, without side effects that, in the opinion of the Investigator or the Medical Monitor, might interfere with participation in the study, pose any added risk to the participant, or confound the assessment of safety or efficacy of the study intervention. • FcRn inhibitor: Received within < 5 half-lives before enrollment on Day 1. Participants receiving prior treatment with an FcRn inhibitor ≥ 5 half-lives before enrollment on Day 1 may be enrolled, but the total IgG level must be above the LLN before these participants can be enrolled. • Rituximab, ocrelizumab, or other B cell-depleting therapy: received or scheduled within ≤ 6 months (180 days) before enrollment on Day 1. Participants receiving prior B cell depleting therapy may be enrolled after this period, but B cell and platelet counts must be above the LLN before enrollment. • Periodic (chronic) administration of PP/PE as maintenance therapy received or scheduled within ≤ 3 months before enrollment on Day 1. However, PP/PE can be used as rescue therapy as described in Section 6.8.3."
12. Participation in another investigational medication, biologics, combination product or device study within 30 days or 5 half-lives of the treatment, whichever is longer, before the first dose of study intervention. Participation in observational studies, for example, MG registry studies, is permitted
13. Positive HIV antibody test or a positive serological test for HIV-1 or HIV-2.
14. Evidence of hepatitis B or hepatitis C viral infection or presence of HBsAg or HBcAb with negative surface antibody (anti-HBs), or HCV infection (HCV antibody positive, expect for participants with document successful treatment). If locally available, SVR should be documented or established at Screening
15. Participants who have a positive pregnancy test at Screening or Day 1.
16. Fever as documented by a body temperature ≥ 38°C (100.4°F) within 7 days prior to Day 1.
17. "Laboratory abnormalities at the Screening Visit, including: a. ALT > 2 × ULN b. Direct bilirubin > 2 × ULN c. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 or participant on dialysis d. Any other clinically significant laboratory abnormality that, in the opinion of the Investigator, would make participation in the study inappropriate or put the participant at undue risk."
18. Pregnant, breastfeeding, or intending to conceive during the course of the study.
19. Participant is an employee or directly related to an employee of Alexion or the institution/investigational site.
20. Participant or caregiver unable or not willing to administer the study intervention.
21. Inability or unwillingness to adhere to the protocol requirements and restrictions, including participation in scheduled study visits.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary PK Estimand: Variables: Serum gefurulimab concentrations from Day 1 predose through Week 18 predose (Cmax, Ctrough) Summary measures: Summary statistics of gefurulimab concentrations at Day 1 predose through Week 18 predose Primary PD Estimand: Variables: Serum free C5 concentrations from Day 1 predose through Week 18 predose Summary measures: Summary statistics of serum free C5 concentrations at Day 1 predose through Week 18 predose

Secondary endpoints 2

1. "• Incidence of TEAEs and TESAEs • Change from Baseline in vital signs, ECG, physical examination, and laboratory assessments • Tolerability of the subcutaneous injection"
2. "• Change from Baseline in QMG total score from Baseline through Week 18 • Proportion of participants with ≥ 5-point reduction compared to Baseline in the QMG total score over time through Week 18 • Change in MG-ADL total score from Baseline through Week 18 • Proportion of participants with ≥ 3-point reduction compared to Baseline in the MG-ADL total score over time through Week 18"

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications