A Clinical Study to Enable Process Validation of Commercial Grade OTL-101

NCT04140539 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: OTL-101-7
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the current study is to treat at least 3 ADA-SCID patients with OTL-101 prepared by the commercial manufacturing process.

Conditions

Severe Combined Immunodeficiency Due to ADA Deficiency

Outcome Measures

Primary Outcomes (3)

• Adenosine Deaminase (ADA) enzyme activity

  ADA enzyme activity in red blood cells

  6 months post treatment

• T cell (CD3+) count

  Absolute count of CD3+ cells

  6 months post treatment

• Vector Copy Number (VCN)

  VCN in granulocytes

  6 months post treatment

Secondary Outcomes (2)

• Overall Survival (OS)

  12 months post treatment

• Event-free Survival (EvFS)

  12 months post treatment

Study Arms (1)

Gene Therapy

EXPERIMENTAL

Infusion OTL-101

Biological: OTL-101

Interventions

OTL-101 BIOLOGICAL

Autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo using a lentiviral vector (LV) encoding the human adenosine deaminase (ADA) gene.

Gene Therapy

Eligibility Criteria

• Age: 30 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Provision of written informed consent by the subject or parent(s)/legal guardian(s), prior to any study related procedures taking place. Where consent is provided by the parent(s)/legal guardian(s), assent by the subject should also be sought, if appropriate
• Age ≥30 days and \<18 years
• Diagnosis of ADA-SCID based on either:
• \) Evidence of ADA deficiency, defined as Decreased ADA enzymatic activity in erythrocytes, leukocytes, skin fibroblasts, or in cultured fetal cells to levels consistent with ADA-SCID as determined by the reference laboratory OR Identified mutations in ADA alleles consistent with a severe reduction in ADA activity
• \) Evidence of ADA-SCID, defined as Family history of a first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency OR Evidence of severe immunologic deficiency in subjects prior to the institution of immune restorative therapy, based on at least one of the following:
• Lymphopenia (absolute lymphocyte count \<400 cells/μL) OR absence or low number of T cells (absolute CD3+ count \< 300 cells/μL)
• Severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (either \<10% of lower limit of normal controls for the diagnostic laboratory, or \<10% of the response of the normal control of the day, or stimulation index \<10)
• Identification of SCID by neonatal screening revealing low T cell receptor excision circles (TREC) levels
• Ineligible for allogeneic bone marrow transplantation from an Human leukocyte antigen (HLA)-identical sibling donor, with normal immune function
• For females of child-bearing potential, negative pregnancy test up to 30 days prior to the Screening visit. For all subjects in the reproductive age range, agreement to use highly effective and adequate method of contraception while receiving treatment and for at least 12 months following drug administration
• Willingness and ability of the subjects and parent(s)/legal guardian(s) to comply with study procedures and requirements, including remaining at the clinic for the required duration of conditioning and treatment and compliance with follow-up evaluations

You may not qualify if:

• Ineligible for autologous HSCT as per clinical site criteria.
• Hematologic abnormality, defined as:
• Anemia (Hb \<8.0 g/dL)
• Neutropenia (absolute neutrophil count (ANC) \<500 cells/mm3). Note: ANC \<500 cells/mm3 with absence of myelodysplastic syndrome on bone marrow aspirate and biopsy and normal marrow cytogenetics are acceptable for eligibility
• Thrombocytopenia (platelet count \<50,000 platelets/mm3)
• Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial thromboplastin time (PTT) \>2 times the upper limit of normal (ULN) (subjects with a correctable deficiency controlled on medication will not be excluded)
• Cytogenetic abnormalities on peripheral blood or bone marrow or amniotic fluid (if available)
• Prior allogeneic HSCT with cytoreductive conditioning
• Pulmonary abnormality, defined as:
• Resting oxygen (O2) saturation by pulse oximetry \<90% on room air
• Chest X-ray indicating active or progressive pulmonary disease. Note: Chest X- ray indicating residual signs of treated pneumonitis is acceptable for eligibility
• Cardiac abnormality, defined as:
• Abnormal electrocardiogram indicating cardiac pathology
• Uncorrected congenital cardiac malformation with clinical symptoms
• Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Severe combined immunodeficiency due to adenosine deaminase deficiency

Study Officials

• Orchard Therapeutics Clinical Trials

  Orchard Therapeutics (Europe) Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: October 28, 2019
• Study Start: October 15, 2019
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2021
• Last Updated: August 3, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)