A First-in-human, Single Ascending Dose Study of GZ402668 in Patients With Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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Primary Objective: To assess the safety and tolerability of GZ402668 after ascending single intravenous (IV) and subcutaneous (SC) doses in men and women with progressive multiple sclerosis. Secondary Objectives: To assess the following in men and women with progressive multiple sclerosis: The pharmacokinetic (PK) parameters of GZ402668 after ascending single IV doses. The pharmacodynamics (PD) of GZ402668 after ascending single IV doses. The PK parameters of GZ402668 after ascending single SC doses. The PD of GZ402668 after ascending single SC doses.

Detailed Description
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The total study duration from screening for a patient can be approximately up to 8 weeks. Upon completion of this trial, patients treated with GZ402668 will be required to enroll in a 4 year safety follow-up study for continued safety observation.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Single Intravenous and Subcutaneous Doses of GZ402668 in Men and Women With Progressive Multiple Sclerosis

Conditions
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Progressive Multiple Sclerosis

Intervention / Treatment
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* Drug: GZ402668
* Drug: placebo
* Drug: GZ402668
* Drug: placebo
* Drug: acyclovir


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female adult with a diagnosis of progressive multiple sclerosis (MS) including primary progressive MS, secondary progressive MS, and progressive relapsing MS. Aged between 18 and 65 years, inclusive. Body weight greater than 40.0 kg. Female patient of child bearing potential must use 2 highly effective contraception methods. Male patient, whose partners are of childbearing potential (including lactating women), must accept to use, during sexual intercourse, 2 highly effective contraception methods. Male patient, whose partners are pregnant, must use, during sexual intercourse, a condom from the inclusion up to 4 months after investigational medicinal product administration. Male patient who has agreed not to donate sperm for 4 months after product administration. Exclusion criteria: Significant medical diseases or conditions, including poorly controlled hypertension, cardiovascular disease, inflammatory disorders, immunodeficiency, autoimmune disease, renal failure, liver dysfunction, cancer (except treated basal skin cell carcinoma), or active infection. Frequent headaches and/or migraine, recurrent nausea and/or vomiting. History or presence of drug or alcohol abuse. Smoking more than 5 cigarettes or equivalent per day. If female, pregnancy, lactating, or breast-feeding. Patients with relapsing-remitting MS. Lymphocyte counts below the lower limit of normal. Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine in the past 6 months. Treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids) in the last 12 months, or determined by the treating physician to have residual immune suppression from these treatments. Treatment with glatiramer acetate or interferon beta in the past 4 weeks. Treatment with fingolimod within the past 2 months. Treatment with dimethyl fumarate in past 4 weeks. Treatment with teriflunomide within the past 12 months unless patient has completed an accelerated clearance with cholestyramine. Previous treatment with alemtuzumab. Live, attenuated vaccine within 3 months prior to the randomization visit, such as varicella-zoster, oral polio, and rubella vaccines. Clinically significant abnormality in thyroid function. Inability to undergo magnetic resonance imaging with gadolinium administration. Hypersensitivity or contraindication to acyclovir. Known bleeding disorder. Significant autoimmune disease. Active infection or at high risk for infection. Latent or active tuberculosis. Major psychiatric disorder that is not adequately controlled by treatment. Epileptic seizures that are not adequately controlled by treatment. Prior history of invasive fungal infections. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1 IV<br>GZ402668 dose 1 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: GZ402668<br>* Pharmaceutical form:solution Route of administration: intravenous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Dose 2 IV<br>GZ402668 dose 2 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: GZ402668<br>* Pharmaceutical form:solution Route of administration: intravenous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Dose 3 IV<br>GZ402668 dose 3 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: GZ402668<br>* Pharmaceutical form:solution Route of administration: intravenous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Dose 3 SC<br>GZ402668 dose 3 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: GZ402668<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Dose 4 SC<br>GZ402668 dose 4 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: GZ402668<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Experimental: Dose 5 SC<br>GZ402668 dose 5 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: GZ402668<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Placebo Comparator: Placebo SC<br>placebo subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: placebo<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|
| Placebo Comparator: Placebo IV<br>placebo intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy | Drug: placebo<br>* Pharmaceutical form:solution Route of administration: intravenous<br>Drug: acyclovir<br>* Pharmaceutical form:tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration (Cmax) |  | 4 weeks | 
| area under curve (AUC) |  | 4 weeks | 
| Number of participants with lymphocyte depletion |  | 4 weeks | 
| Number of participants with anti-drug antibodies |  | 4 weeks | 
| Number of participants with injection site reactions |  | 2 weeks | 
| Number of participants with corrected QT interval (QTcF) prolongation |  | 4 weeks |