Phase 1b/2 Study of IM-101 in Adult Participants with Generalized and Ocular Myasthenia Gravis
- Trial ID
- 2025-522406-20-00
- Protocol
- IM-101_MG_2.1
- Sponsor
- Immunabs Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the safety and tolerability of IM-101 in adult participants with AChR antibody-positive generalized myasthenia gravis (gMG) through multiple ascending dose regimens. Additionally, the study aims to assess the efficacy and safety of IM-101 compared to a placebo in participants with AChR antibody-positive gMG, AChR antibody-negative gMG, and ocular myasthenia gravis (oMG). The investigation also includes the assessment of pharmacokinetics and pharmacodynamics in the ascending dose cohorts.
Secondary objectives include the following:
- Assessment of immunogenicity in participants with gMG (AChR antibody-positive, AChR antibody-negative, or oMG).
- Further evaluation of safety and tolerability across the expanded participant cohorts.
- Characterization of exposure to IM-101.
- Evaluation of changes in pharmacodynamic biomarkers following exposure to the study drug.
Participants
This study involves 52 participants diagnosed with myasthenia gravis, including both generalized myasthenia gravis and ocular myasthenia gravis. The study population consists of male and female individuals aged 18 to 74 years with a body weight of at least 40 kg. Eligible participants must have experienced the onset of muscle weakness after age 16 and have received an acquired diagnosis at least 6 months prior to screening. Specific inclusion requirements based on disease subtype include:
- AChR antibody-positive participants must demonstrate the presence of anti-AChR binding antibody.
- AChR antibody-negative participants must be negative for the binding antibody.
- Participants with ocular myasthenia gravis must meet MGFA Clinical Classification Class I and possess an MG-ADL score of 3 to 6 attributed exclusively to ocular elements.
Plans and Procedures
This Phase 1b/2, multicenter, randomized, double-blind, placebo-controlled study is designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IM-101 in adults with myasthenia gravis. The research is divided into two parts: Part A involves multiple ascending dose cohorts to assess safety and tolerability across three different dose regimens, while Part B consists of expansion cohorts to evaluate both efficacy and safety in participants with generalized myasthenia gravis (including AChR antibody-positive and AChR antibody-negative subtypes) and ocular myasthenia gravis. The study protocol includes a screening visit for eligibility assessment, followed by periods of administration and follow-up assessments to monitor clinical changes and treatment-emergent adverse events. Primary efficacy endpoints for the expansion cohorts include changes in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score or the MGII ocular score at Week 16. Participant involvement is subject to monitoring of safety parameters, and early discontinuation of the study intervention may occur due to adverse events or other clinical requirements.
Treatment
IM-101 is an experimental solution for infusion at a concentration of 120 mg/mL. It is administered via intravenous injection to investigate safety, tolerability, pharmacokinetics, and pharmacodynamics in participants with myasthenia gravis.
The placebo consists of 0.9% sodium chloride administered through intravenous administration.
Auxiliary background treatments include several vaccines administered via intramuscular injection: Prevenar 13, a pneumococcal polysaccharide conjugate vaccine; Menveo, a meningococcal conjugate vaccine; Bexsero, a meningococcal group B vaccine; and Infanrix hexa, a hexavalent vaccine containing diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type b.
Efficacy
The efficacy of IM-101 in participants with generalized myasthenia gravis (gMG) and ocular myasthenia gravis (oMG) is evaluated through several clinical parameters. In the gMG cohorts, the primary efficacy assessment is the change from baseline to Week 16 in the MG-ADL total score. Secondary efficacy assessments for gMG include changes from baseline to Week 16 in the QMG total score, the MGC scale, and the MG-QoL15r. Additionally, the percentage of participants achieving a MG-ADL change of $\ge$ 2 points or $\ge$ 3 points at Week 16, as well as the percentage achieving minimal symptomatic state (MSE) or an MG-ADL score of 0 or 1, will be measured. For the oMG cohort, efficacy is assessed by the change from baseline to Week 16 in the MGII ocular domain, the MGII total score, and the quantitative change from baseline in the QMG total score. The percentage of participants requiring rescue therapy over the 16-week treatment period is also monitored across all cohorts.
The assessment of immunogenicity and pharmacodynamics includes the following:
- Incidence and prevalence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAb) to IM-101 over time.
- Measurement of CH50, AH50, total C5, and free C5 levels at baseline and at specific timepoints during and after treatment.
- Evaluation of serum IM-101 concentrations over the treatment period, including sparse sample collections to support population pharmacokinetics modeling and simulations.
Inclusion and Exclusion Criteria
Inclusion Criteria
- All Participants Able and willing to provide signed informed consent and willing to travel to the investigational sites for study visits and fulfill logistical requirements of study
- Willingness to consent to screening for genetic muscular diseases (mitochondrial myopathy, oculopharyngeal muscular dystrophy, congenital myasthenia syndrome, and progressive external ophthalmoplegia)
- Male or female aged ≥ 18 years and < 75 years
- Has no known weakness in infancy and develop muscle weakness after aged 16 years and diagnosed with acquired MG at least 6 months (180 days) prior to the date of the screening visit (signing of informed consent)
- Diagnosed with MG, confirmed through: a. Abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation, or b. Positive response to an AChEI test (eg, edrophonium chloride test), or c. Improvement of signs or symptoms related to MG during treatment with an oral acetylcholinesterase inhibitor, as determined by the treating physician (pyridostigmine or neostigmine or edrophonium test)
- Body weight ≥ 40 kg at screening
- On a stable dose of background therapy for the treatment of MG for the time periods specified below, with no changes to the regimen expected during the treatment period: a. Oral corticosteroids: stable for ≥ 4 weeks before Day 1 with the daily dose not exceeding 20 mg/day for prednisone/prednisolone or 16 mg/day for methylprednisolone. b. Acetylcholinesterase inhibitors: stable for ≥ 4 weeks prior to randomization c. Azathioprine, mycophenolate mofetil, methotrexate: receiving for ≥ 6 months prior to screening, with a stable dose for ≥ 3 month prior to randomization. If discontinued prior to screening, participants must have stopped azathioprine, mycophenolate mofetil or methotrexate ≥ 12 weeks prior to Day 1
- Vaccinated against meningococcal infection (Neisseria meningitidis) within 1 year of screening, and at least 2 weeks prior to Day 1 (participants must have received 2 doses of vaccine to be considered vaccinated)
- Vaccinated against streptococcus pneumoniae, and haemophilus influenzae type B according to local standard
- Female participants of childbearing potential (ie, women who are not postmenopausal or who have not had a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) and male participants who have not been surgically sterilized by a vasectomy must use a reliable and highly effective contraception method throughout the study and for 3 months after the last dose of study intervention
- Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to the first dose of study intervention
- All gMG Participants Myasthenia Gravis – Activities of Daily Living (MG-ADL) total score ≥ 6 at both screening and randomization, with at least 50% of the score attributed to non-ocular elements
- All gMG Participants Myasthenia Gravis Foundation of America (MGFA) Class II to IVa classification.
- AChR Antibody-positive gMG Participants Only Must have anti-AChR binding antibody.
- AChR Antibody-negative gMG Participants Only AChR-binding antibody negative.
- oMG Participants Only MGFA Clinical Classification Class I
- oMG Participants Only MG-ADL total score 3 to 6 at both screening and randomization, assigned exclusively to ocular elements.
Exclusion Criteria
- All Participants Previous exposure to IM-101
- Anti-MuSK antibody Positive
- History of thymectomy, or any other thymic surgery within 12 months prior to screening or planned during the study
- History of malignant thymoma (patients with Stage I may be enrolled), or history of cancer within the past 5 years of screening, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervix cancer
- History of any immunologic disorder other than MG, or any other conditions that would interfere with an accurate assessment of clinical gMG or oMG or that would require chronic oral, intravenous, intramuscular, or intra-articular corticosteroid therapy. Well-controlled thyroid disease, as per the Investigator or the participant’s regular treating physician recorded in the source documents, is not exclusionary
- History of, or current diagnosis of active tuberculosis (TB), or currently undergoing treatment for latent TB, or untreated latent TB infection as determined by results within 3 months of the screening visit of a positive TB skin test with purified protein derivative with induration ≥ 5 mm. Additionally, the participant should be excluded if they have current household contacts with active TB, or the participant has a positive QuantiFERON TB Gold test at screening unless they have completed chemoprophylaxis for the latent TB infection (as per applicable local guidelines) prior to the screening visit.
- History of N. meningitidis infection
- Clinical features that, in the opinion of the Investigator, are consistent with gMG crisis/exacerbation or clinical deterioration, within 28 days prior to randomization (Day 1)
- History of hypersensitivity to any ingredient contained in the study intervention
- Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to screening
- Evidence of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV-1 or HIV-2) viral infection at screening
- Active systemic bacterial, viral, or fungal infection within 14 days prior to first dose of the study intervention
- Presence of fever as documented by a temperature ≥ 37.8°C (100.04°F) by oral or ≥ 37.3°C (99.14°F) by skin (axillary) or ≥ 38.3°C (100.94°F) by tympanic within 7 days prior to the first dose of the study intervention
- Use of the following within the time periods specified: a. Intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin within the 4 weeks prior to screening b. Use of plasma exchange (PLEX) within 4 weeks prior to screening c. Use of rituximab, tacrolimus, or cyclophosphamide within 6 months prior to screening d. Use of neonatal Fc receptor (FcRn) blocker within 6 weeks prior to screening e. Use of C5 inhibitor approved for the treatment of gMG at the recommended dose regimen for within 2 months (zilucoplan or eculizumab) or 3 months (ravulizumab) prior to screening
- Has been treated with any complement inhibitor, but failed due to intolerability or lack of efficacy
- Clinical laboratory abnormalities at screening, including: a. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 × the upper limit of normal (ULN) b. Total bilirubin > 1.5 × ULN c. Estimated glomerular filtration rate < 60 mL/min/1.73 m2 based on the Modification of Diet in Renal Disease equation
- Participation in another interventional treatment study or use of any experimental therapy within 30 days before screening or within 5 half-lives of the study drug, whichever is longer
- Pregnant, breastfeeding, or intending to conceive during the course of the study
- Planned surgical procedure requiring general anesthesia during the course of the study
- Any medical or psychological condition(s), clinically significant laboratory abnormality 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 the participant or outcome of the study.
- oMG Participants Only Participant with fixed ophthalmoplegia
- oMG Participants Only History of eyelid retraction surgery
- oMG Participants Only Family history of clinically meaningful ptosis or diplopia or other known diseases that lead to eyelid drooping, peripheral muscle weakness, or diplopia.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 19 Jan 2026 | 22 |
 Italy | Recruiting | 19 Jan 2026 | 15 |
 Poland | Recruiting | 19 Jan 2026 | 32 |
 Spain | Recruiting | 19 Jan 2026 | 14 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IM-101 120mg/mL | Test | SOLUTION FOR INFUSION | INTRAVENOUS INJECTION | — | — | PRD12783133 |
Infanrix hexa, Powder and suspension for suspension for injection. Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (adsorbed). | Other | POWDER AND SUSPENSION FOR SUSPENSION FOR INJECTION | INTRAMUSCULAR USE | — | — | PRD344809 |
Prevenar 13 suspension for injection pneumococcal polysaccharide conjugate vaccine13-valent, adsorbed | Other | SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | — | — | PRD3342243 |
0.9% Sodium ChlorideNormal Saline | Placebo | N/A | INTRAVENOUS | — | — | N/A |
Bexsero suspension for injection in pre-filled syringe Meningococcal group B VaccinerDNA, component, adsorbed | Other | SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE | INTRAMUSCULAR USE | — | — | PRD2149122 |
Menveo powder and solution for solution for injection Meningococcal Group A, C, W-135 and Y conjugate vaccine | Other | POWDER AND SOLUTION FOR SOLUTION FOR INJECTION | INTRAMUSCULAR USE | — | — | PRD2149158 |