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

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

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.

Study Overview

• Status: Completed
• Conditions: Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: GZ402668; Drug: GZ402668; Drug: acyclovir; Drug: placebo; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Investigational Site Number 276001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: October 31, 2014
• First Submitted That Met QC Criteria: November 3, 2014
• First Posted (Estimate): November 4, 2014

Study Record Updates

• Last Update Posted (Estimate): April 13, 2016
• Last Update Submitted That Met QC Criteria: April 12, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Anti-Infective Agents; Antiviral Agents; Acyclovir
• Other Study ID Numbers: TDU13475; 2014-001591-61 (EudraCT Number); U1111-1155-6252 (Other Identifier: UTN)