Study on the Safety and Tolerability of DNTH103 for Adults with Generalized Myasthenia Gravis

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What is this study about?

This clinical trial is focused on studying a condition called Generalized Myasthenia Gravis (gMG), which is a chronic autoimmune disease that causes muscle weakness. The study will evaluate a treatment known as DNTH103, a monoclonal antibody, to see how safe and tolerable it is for patients with this condition. A monoclonal antibody is a type of protein made in a lab that can bind to substances in the body, including cancer cells. The trial will also include a placebo, which is a substance with no active medication, to compare the effects of DNTH103.

The purpose of the study is to assess the safety and tolerability of DNTH103 in adults with gMG over a period of 13 weeks. Participants will receive either DNTH103 or a placebo through intravenous (IV) or subcutaneous (SC) injections. The study will monitor the participants for any side effects and measure the levels of DNTH103 in their blood. Additionally, the study will evaluate the effectiveness of DNTH103 in improving symptoms of gMG by using various scales that measure muscle strength and daily living activities.

Participants in the study will be adults aged 18 to 75 who have been diagnosed with gMG for at least three months. They will need to have received certain vaccinations against bacterial infections before joining the study. The trial will last up to 52 weeks, with the main focus on the first 13 weeks. During this time, the safety and any potential side effects of DNTH103 will be closely monitored. The study aims to provide valuable information on the potential benefits and risks of using DNTH103 for treating gMG.

1 Joining the study

Upon joining the study, the participant will be randomly assigned to receive either the investigational drug DNTH103 or a placebo. This process is blinded, meaning neither the participant nor the study team will know which treatment is being administered.

2 Initial treatment phase

The participant will receive the assigned treatment through intramuscular injection. The specific schedule and dosage will be determined by the study protocol and communicated to the participant at the start of the trial.

3 Monitoring and assessments

Throughout the study, the participant will undergo regular assessments to monitor safety and tolerability. This includes checking for any side effects and evaluating the participant’s response to the treatment.

The participant will also complete various scales and questionnaires to assess the impact of the treatment on their condition, such as the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale.

4 Vaccination requirements

Participants must have documented vaccinations against certain bacterial infections, including N. meningitidis and S. pneumoniae, within three years prior to enrollment or be vaccinated at least two weeks before randomization.

5 End of randomized controlled trial period

The initial phase of the study will last up to 13 weeks. During this time, the primary focus will be on evaluating the safety and tolerability of the treatment.

At the end of this period, the participant’s progress will be reviewed, and further participation in the study may be discussed.

6 Open-label extension phase

Participants may have the opportunity to continue in an open-label extension phase, where all participants receive the investigational drug DNTH103. This phase will last up to 52 weeks.

The focus will be on long-term safety and effectiveness, with continued monitoring and assessments.

Who Can Join the Study?

Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
Participants must be receiving at least 1 but not more than 3 of the following immunosuppressant medications at Screening, provided they have a stable daily dose for the minimum periods outlined below and maintain throughout the study:
- If taking oral corticosteroids, must have been taking for at least 4 weeks (28 days) prior to randomization, with doses not to exceed an average of 40 mg/day (280 mg/week) of prednisone or its equivalent.
- If taking azathioprine, must have been taking for at least 6 months (180 days) at time of randomization with a stable dose for at least 2 months (60 days) prior to randomization.
- If taking other immunosuppressants, must have been on other immunosuppressants (such as cyclosporin, mycophenolate mofetil, cyclophosphamide, or methotrexate) for at least 3 months (90 days) at time of randomization with a stable dose for at least 1 month (30 days) prior to randomization.
Female participants must:
- Be of nonchildbearing potential, meaning they are surgically sterilized or postmenopausal (no menstrual periods for 12 months without another medical reason).
- If of childbearing potential, must agree not to donate eggs, not to attempt to become pregnant, and if engaging in sexual intercourse with a male partner, must agree to use a highly effective method of contraception from signing the informed consent form throughout the study until the end of the Safety Follow-up period, or longer if required in accordance with local requirements.
Male participants must be surgically sterile for at least 90 days prior to Screening or agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the informed consent form throughout the study until the end of the Safety Follow-up period, or longer if required in accordance with local requirements.
No clinically significant abnormalities (in the opinion of the Investigator) during Screening, including:
- No clinically significant findings in blood and urine tests.
- Electrocardiogram (ECG), a test that checks the heart’s electrical activity, must show no significant abnormalities.
Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Adult males and females, 18 to 75 years of age (inclusive) at Screening.
Weight range between 40-120 kg at Screening.
Diagnosed with generalized myasthenia gravis (gMG) at least 3 months (90 days) before the Screening visit.
Diagnosis of gMG by the following tests:
- Acetylcholine receptor antibody (AChR Ab) positive as confirmed during the Screening period prior to randomization.
- One of the following:
  - History of abnormal neuromuscular transmission test, which checks how well nerves and muscles communicate, consistent with gMG.
  - History of positive anticholinesterase test, a test that checks the effect of certain medications on muscle strength.
  - Clinical response to acetylcholinesterase inhibitors such as pyridostigmine (Mestinon®) as assessed by the treating physician.
Myasthenia Gravis Foundation of America (MGFA) Class II-IVa, at Screening and confirmed at randomization.
Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or more, at Screening and confirmed at randomization.
Participants must have documented vaccinations against certain bacteria within 3 years of enrollment or be vaccinated at least 2 weeks (14 days) prior to randomization.
Participants using acetylcholinesterase inhibitors (e.g., pyridostigmine, Mestinon) at Screening are allowed to continue provided they maintain a stable daily dose for a minimum period of 2 weeks (14 days) prior to randomization.

Who Cannot Join the Study?

Patients who have a history of severe allergic reactions to any of the ingredients in the study medication.
Patients who are currently participating in another clinical trial.
Patients who have had a recent infection that required treatment with antibiotics.
Patients who have a history of drug or alcohol abuse.
Patients who are pregnant or breastfeeding.
Patients who have any other medical condition that the study doctor believes would make it unsafe for them to participate.
Patients who have received certain treatments for myasthenia gravis within a specific time frame before the study.
Patients who have a history of certain types of cancer.
Patients who have uncontrolled high blood pressure.
Patients who have a history of heart problems, such as a heart attack or heart failure.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Bellvitge University Hospital	L'hospitalet De Llobregat	Spain
Hospital Universitario Y Politecnico La Fe	Valencia	Spain
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Galen Clinic	Lublin	Poland
Neurologia Slaska Centrum Medyczne	Katowice	Poland

Other Sites

Site Name	City	Country
Region Stockholm – SLSO	Stockholm	Sweden
University Of Skane	Malmo	Sweden
Universita’ Di Pisa	Pisa	Italy
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie	Cracow	Poland
Centre Hospitalier Universitaire De Nice	Nice	France
Rigshospitalet	Copenhagen	Denmark
Neuroprotect Sp. z o.o.	Warsaw	Poland
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
University Hospital Ostrava	Ostrava	Czechia
Cmxevrvd Syx z opfd	Warsaw	Poland
Rwdqxryauuyqfxop Hwadgvrs	Garches	France
Mwtoqvxvi Imimmvhdla Cobvrihr Seantfga Sce z ocol	Warsaw	Poland
Aqzdcsllr Urf	Amsterdam	The Netherlands
Hmcia Bmctma Hw	Bergen	Norway
Fkucdvcfx Prdl Ls Iatvwtorgoanm Bzglxkvgs Dks Hzadjuvr Ucrcubfznsmhh Lu Pbb	Madrid	Spain
Hzemssjx Vwni dlcfdxoq	Barcelona	Spain
Kqwxqqpcl Sbvguip Sqzqptklgqzvvno ix Jnlq Pitao Ip	Cracow	Poland
Hgtdytmn Ufemkkrkixqbhc Sltyvvymun &azwuhd Hdtfnkz dr Hexrscgkfuq	STRASBOURG, Alsace	France

Trial status

Country	Status	Recruitment Start
Czechia	Not recruiting	17.06.2024
Denmark	Not recruiting	17.06.2024
France	Not recruiting	17.06.2024
Italy	Not recruiting	17.06.2024
Norway	Not recruiting	17.06.2024
Poland	Not recruiting	17.06.2024
Spain	Not recruiting	17.06.2024
Sweden	Not recruiting	17.06.2024
The Netherlands	Not recruiting	17.06.2024

Trial locations

Investigated drugs:

DNTH103 is a medication being studied for its safety and effectiveness in treating adults with generalized myasthenia gravis, a condition that causes muscle weakness. The trial aims to understand how well patients tolerate this medication and its potential benefits in managing the symptoms of the disease over a period of 13 weeks.

Investigated diseases:

Myasthenia gravis

Generalized Myasthenia Gravis – Generalized Myasthenia Gravis is a chronic autoimmune disorder that affects the communication between nerves and muscles, leading to muscle weakness. It occurs when the immune system mistakenly attacks the body’s own tissues, specifically targeting the receptors that receive nerve signals. This results in fluctuating muscle weakness and fatigue, which can affect various muscle groups, including those responsible for eye movement, facial expression, chewing, talking, and swallowing. The severity of symptoms can vary, often worsening with activity and improving with rest. Over time, the condition may lead to more persistent muscle weakness, impacting daily activities and quality of life.

Trial ID:

2024-512865-15-00

Protocol code:

DNTH103-MG-201

NCT ID:

NCT06282159

Trial Phase:

Therapeutic exploratory (Phase II)

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Study on the Safety and Tolerability of DNTH103 for Adults with Generalized Myasthenia Gravis

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