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

Primary Purpose

Progressive Multiple Sclerosis

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
GZ402668
placebo
GZ402668
placebo
acyclovir
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Multiple Sclerosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 276001

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Dose 1 IV

Dose 2 IV

Dose 3 IV

Dose 3 SC

Dose 4 SC

Dose 5 SC

Placebo SC

Placebo IV

Arm Description

GZ402668 dose 1 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

GZ402668 dose 2 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

GZ402668 dose 3 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

GZ402668 dose 3 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

GZ402668 dose 4 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

GZ402668 dose 5 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

placebo subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

placebo intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy

Outcomes

Primary Outcome Measures

Number of participants with treatment emergent adverse events

Secondary Outcome Measures

maximum concentration (Cmax)
area under curve (AUC)
Number of participants with lymphocyte depletion
Number of participants with anti-drug antibodies
Number of participants with injection site reactions
Number of participants with corrected QT interval (QTcF) prolongation

Full Information

First Posted
October 31, 2014
Last Updated
April 12, 2016
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT02282826
Brief Title
A First-in-human, Single Ascending Dose Study of GZ402668 in Patients With Progressive Multiple Sclerosis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose 1 IV
Arm Type
Experimental
Arm Description
GZ402668 dose 1 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Arm Title
Dose 2 IV
Arm Type
Experimental
Arm Description
GZ402668 dose 2 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Arm Title
Dose 3 IV
Arm Type
Experimental
Arm Description
GZ402668 dose 3 intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Arm Title
Dose 3 SC
Arm Type
Experimental
Arm Description
GZ402668 dose 3 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Arm Title
Dose 4 SC
Arm Type
Experimental
Arm Description
GZ402668 dose 4 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Arm Title
Dose 5 SC
Arm Type
Experimental
Arm Description
GZ402668 dose 5 subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Arm Title
Placebo SC
Arm Type
Placebo Comparator
Arm Description
placebo subcutaneous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Arm Title
Placebo IV
Arm Type
Placebo Comparator
Arm Description
placebo intravenous, single administration. Acyclovir 200 mg twice daily for 28 days as prophylactic therapy
Intervention Type
Drug
Intervention Name(s)
GZ402668
Intervention Description
Pharmaceutical form:solution Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Pharmaceutical form:solution Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
GZ402668
Intervention Description
Pharmaceutical form:solution Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Pharmaceutical form:solution Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
acyclovir
Intervention Description
Pharmaceutical form:tablet Route of administration: oral
Primary Outcome Measure Information:
Title
Number of participants with treatment emergent adverse events
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
maximum concentration (Cmax)
Time Frame
4 weeks
Title
area under curve (AUC)
Time Frame
4 weeks
Title
Number of participants with lymphocyte depletion
Time Frame
4 weeks
Title
Number of participants with anti-drug antibodies
Time Frame
4 weeks
Title
Number of participants with injection site reactions
Time Frame
2 weeks
Title
Number of participants with corrected QT interval (QTcF) prolongation
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 276001
City
Berlin
ZIP/Postal Code
10117
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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